leptin and Infertility--Male

Despite its important role in numerous physiological functions, including regulation of appetite and body weight, immune function and normal sexual maturation, raised leptin levels could result in significant damaging effects on sperm. The adverse effects of leptin on the male reproductive system result from its direct actions on the reproductive organs and cells instead of the hypothalamus-pituitary-gonadal axis. Binding of leptin to the receptors in the seminiferous tubular cells of the testes increases free radical production and decreases the gene expression and activity of endogenous enzymatic antioxidants. These effects are mediated via the PI3K pathway. The resultant oxidative stress causes significant damage to the seminiferous tubular cells, germ cells and sperm DNA leading to apoptosis, increased sperm DNA fragmentation, decreased sperm count, increased fraction of sperm with abnormal morphology, and decreased seminiferous tubular height and diameter. This review summarises the evidence in the literature on the adverse effects of leptin on sperm, which could underlie the often-reported sperm abnormalities in obese hyperleptinaemic infertile males. Although leptin is necessary for normal reproductive function, its raised levels could be pathologic. There is, therefore, a need to identify the cut-off level in the serum and seminal fluid above which leptin becomes pathological for better management of leptin associated adverse effects on male reproductive function.

Topics: Antioxidants; Humans; Infertility, Male; Leptin; Male; Obesity; Phosphatidylinositol 3-Kinases; Semen; Sperm Count; Sperm Motility; Spermatozoa

Over the past decades, obesity and infertility in men increased in parallel, and the association between both phenomena have been examined by several researchers. despite the fact that there is no agreement, obesity appears to affect the reproductive potential of men through various mechanisms, such as changes in the hypothalamic-pituitary-testicular (HPT) axis, spermatogenesis, sperm quality and/or alteration of sexual health. Leptin is a hormone produced by the adipose tissue, and its production elevates with increasing body fat. Many studies have supported the relationship between raised leptin production and reproductive function regulation. In fact, Leptin acts on the HPT axis in men at all levels. However, most obese men are insensitive to increased production of endogenous leptin and functional leptin resistance development. Recently, it has been recommended that Kisspeptin neurons mediate the leptin's effects on the reproductive system. Kisspeptin binding to its receptor on gonadotropin-releasing hormone (GnRH) neurons, activates the mammal's reproductive axis and stimulates GnRH release. Increasing infertility associated with obesity is probably mediated by the Kisspeptin-GnRH pathway. In this review, the link between obesity, kisspeptin, leptin, and male fertility will be discussed.

Topics: Fertility; Gonadotropin-Releasing Hormone; Humans; Infertility, Male; Kisspeptins; Leptin; Male; Obesity; Semen

Obesity resulted by imbalance between the intake of energy and energy consumption can lead to growth and metabolic disease development in people. Both in obese men and animal models, several studies indicate that obesity leads to male infertility.. This review has discussed some mechanisms involved in obesity-induced male infertility.. Online documents were searched through Science Direct, Pubmed, Scopus, and Google Scholar websites dating from 1959 to recognize studies on obesity, kisspeptin, leptin, and infertility.. Obesity induced elevated inflammatory cytokines and oxidative stress can affect male reproductive functions, including spermatogenesis disorders, reduced male fertility power and hormones involved in the hypothalamus-pituitary-gonadal axis.. There is significant evidence that obesity resulted in male infertility. Obesity has a negative effect on male reproductive function via several mechanisms such as inflammation and oxidative stress.

Topics: Animals; Humans; Infertility, Male; Leptin; Male; Metabolic Diseases; Obesity; Oxidative Stress

Infertility is somewhat more prevalent in men who are obese. They are also reported to have low sperm concentration, higher fraction of spermatozoa that look morphologically abnormal, higher DNA fragmentation index and evidence of oxidative stress. The precise cause for this remains uncertain. Leptin levels in serum and percentage body fat correlate positively, and obese men therefore usually have elevated serum leptin levels. Although leptin is important for normal reproductive function, but when present in excess, leptin could seriously affect reproductive function in men. Reports on the findings of sperm parameters in obese men, particularly those who are subfertile or infertile, seem to be similar to those reported from studies on normal-weight rats treated with leptin. Collectively, the observations reported in human and experimental animal studies point to leptin as a possible link between infertility and obesity. Herein, we review some findings on sperm function in obese subfertile or infertile men and those from animal studies following leptin treatment, and discuss the possible link between leptin and reproductive dysfunction in obese men. The large amounts of leptin secreted by the adipose tissue and its higher circulating levels could indeed be responsible for the higher prevalence of infertility in obese men.

Topics: Animals; Disease Models, Animal; Humans; Infertility, Male; Leptin; Male; Obesity; Prevalence; Rats; Sperm Count; Sperm Motility

Low sperm concentration, increased fraction of morphologically abnormal sperm, and raised levels of markers of oxidative stress are often reported in the seminal plasma of infertile obese males. The precise reason for changes remains unknown. This short review summarises evidence from human and animal studies linking leptin to the reproductive dysfunction reported in obese males and presents a possible mechanism for this based on the available data in the literature. Serum leptin concentrations correlate positively with body fat mass but its precise link to semen abnormalities reported in obese males has yet to be conclusively established. Decreased sperm concentration, increased fraction of morphologically abnormal sperm and increased markers of oxidative stress have been reported following six weeks of daily leptin treatment to normal weight rats. In addition, decreased expression of endogenous antioxidant enzymes and increased expression of respiratory chain enzymes noted in the testes of leptin treated rats increases the propensity to oxidative stress. Besides that, leptin's interference with histone to protamine transition in the DNA of sperm increases the susceptibility of sperm to free radical attack and may explain the often reported higher DNA fragmentation index in sperm of obese males. Concurrent supplementation of melatonin, a natural anti-oxidant, to these rats prevents the effects of leptin. The role of leptin in obesity-related reproductive dysfunction has to be considered seriously and these effects of leptin might involve increased oxidative stress.

Topics: Animals; Humans; Infertility, Male; Leptin; Male; Obesity; Reproduction

Several studies suggest a strong association between leptin, obesity, and infertility with respect to the hypothalamic-pituitary-gonadal (HPG) axis, androgen regulation, and sperm production, but the direct mechanistic association between these is still largely unexplored. This review focuses on understanding the association between leptin, obesity, and male infertility.. Obesity is linked to fertility dysfunction in both genders. Obesity in men may affect their fertility by impaired spermatogenesis, reduced testosterone levels, erectile dysfunction, and poor libido by putatively targeting the HPG and hypothalamic-pituitary-adrenal axes. Leptin plays key roles in many metabolic functions, including reproduction. High concentrations of leptin have been found in infertile men with disorders affecting the testicular parenchyma, including nonobstructive azoospermia, oligozoospermia, and oligo-astheno-teratozoospermia. Additionally, serum leptin levels have negative associations with serum testosterone levels and sperm parameters and positive associations with serum follicle-stimulating hormone and luteinizing hormone levels and abnormal sperm morphology.. Excessive leptin production may be a significant contributor to the development of androgen insufficiency and reduced reproductive function in obese men. Understanding the relation between leptin, obesity, and reproduction may shed light on future targeted treatments for male infertility.

Topics: Body Mass Index; Female; Humans; Hypothalamo-Hypophyseal System; Infertility, Male; Leptin; Male; Obesity

Obesity stands as one of the greatest healthcare challenges of the 21

Topics: Animals; Female; Humans; Infertility, Male; Leptin; Male; Obesity; Reproductive Health; Spermatogenesis; Testis

Obesity is rising to unprecedented numbers, affecting a growing number of children, adolescents and young adult men. These individuals face innumerous health problems, including subfertility or even infertility. Overweight and obese men present severe alterations in their body composition and hormonal profile, particularly in ghrelin, leptin and glucagon-like peptide-1 (GLP-1) levels. It is well known that male reproductive health is under the control of the individual's nutritional status and also of a tight network of regulatory signals, particularly hormonal signaling. However, few studies have been focused on the effects of ghrelin, leptin and GLP-1 in male reproduction and how energy homeostasis and male reproductive function are linked. These hormones regulate body glucose homeostasis and several studies suggest that they can serve as targets for anti-obesity drugs. In recent years, our understanding of the mechanisms of action of these hormones has grown significantly. Curiously, their effect on male reproductive potential, that is highly dependent of the metabolic cooperation established between testicular cells, remains a matter of debate. Herein, we review general concepts of male fertility and obesity, with a special focus on the effects of ghrelin, leptin and GLP-1 on male reproductive health. We also discuss the possible pharmacological relevance of these hormones to counteract the fertility problems that overweight and obese men face.

Topics: Adolescent; Child; Fertility; Ghrelin; Glucagon-Like Peptide 1; Humans; Infertility, Male; Leptin; Male; Obesity; Overweight; Young Adult

Hypothyroidism is a condition in which the serum levels of thyroid hormones are below that necessary to carry out physiological functions in the body. Hypothyroidism is related to obesity as an increase in body weight gain is seen in hypothyroid patients. Moreover, an inverse correlation between free thyroxine values and body mass index has been reported. Leptin, a polypeptide hormone produced by adipocytes, was originally thought to be an antiobesity hormone due its anorexic effects on hypothalamic appetite regulation. However, nowadays it is known that leptin conveys information about the nutritional status to the brain being considered a crucial endocrine factor for regulating several physiological processes including reproduction. Since the identification of thyroid hormone and leptin receptors on the testes, these hormones are being recognized as having important roles in male reproductive functions. A clear link exists among thyroid hormones, leptin and reproduction. Both hormones can negatively affect spermatogenesis and consequently may cause male infertility. The World Health Organization (WHO) estimates the overall prevalence of primary infertility ranging from 8 to 15%. The fact that 30% of couples' inability to conceive is related to a male factor and that the longer hypothyroidism persisted, the greater the damage to the testes, strongly suggest that more studies attempting to clarify both hormones actions directly in the testes need to be conducted specially in cases of congenital hypothyroidism. Therefore, the goal of this review is to highlight the relationship of such hormones in the reproductive system.

Topics: Animals; Humans; Hypothyroidism; Infertility, Male; Leptin; Male; Obesity; Reproduction; Thyroid Hormones

The increase in obesity rate is a major public health issue associated with increased pathological conditions such as type 2 diabetes or cardiovascular diseases. Obesity also contributes to decreased testosterone levels in men. Indeed, the adipose tissue is an endocrine organ which produces hormones such as leptin, adiponectin and resistin. Obesity results in pathological accumulations of leptin and resistin, whereas adiponectin plasma levels are markedly reduced, all having a negative impact on testosterone synthesis. This review focuses on current knowledge related to transcriptional regulation of Leydig cells' steroidogenesis by leptin, adiponectin and resistin. We show that there are crosstalks between the regulatory mechanisms of these hormones and androgen production which may result in a dramatic negative influence on testosterone plasma levels. Indeed leptin, adiponectin and resistin can impact expression of different steroidogenic genes such as Star, Cyp11a1 or Sf1. Further investigations will be required to better define the implications of adipose derived hormones on regulation of steroidogenic genes expression within Leydig cells under physiological as well as pathological conditions.

Topics: Adiponectin; Adipose Tissue; Body Mass Index; Gene Expression Regulation; Humans; Infertility, Male; Leptin; Leydig Cells; Male; Models, Biological; Obesity; Resistin; Signal Transduction

Obesity is a major health problem contributing to increased subfertility in males, as well as increased morbidity for diseases related to a decline in testosterone production with aging. Leptin is a hormone produced by adipose tissue whose production increases with the amount of body fat. Several studies have supported a relationship between increased leptin production and regulation of reproductive function. Indeed, leptin acts at all levels of the hypothalamus-pituitary-gonadal (HPG) axis in males. However, most of the obese individuals become insensitive to increased endogenous leptin production and develop a functional leptin resistance. This deregulation of leptin signaling might result in abnormal endocrine and reproductive functions. Altered leptin dynamics may contribute to male infertility in different ways, leading to hypogonadism. These include leptin resistance or leptin insufficiency at the hypothalamus and leptin modulation of testicular physiology. In this review, we address the mechanisms of action of leptin at different levels of the HPG axis. Moreover, the influences of leptin on steroidogenesis and spermatogenesis, as well as seasonal variations of leptin's action on male reproduction are discussed.

Topics: Animals; Humans; Hypothalamo-Hypophyseal System; Infertility, Male; Leptin; Leydig Cells; Male; Obesity; Receptors, Leptin; Seasons; Spermatogenesis; Testosterone

Underlying causes of hypogonadotropic hypogonadism are acquired or congenital disorders of the hypothalamus or pituitary (e.g. pituitary adenoma, craniopharyngioma, prior radiotherapy, trauma, severe general diseases, extreme stress, genetic mutations). In addition to a comprehensive history and physical examination, the diagnostic work-up includes measurement of testosterone, LH and FSH, with the aim of differentiating between primary and secondary hypogonadism. Where indicated, investigation of pituitary function, the use of imaging procedures, possibly an olfactory test, a GnRH stimulation test or genetic analyses may be added. Depending upon the indication, treatment is effected with testosterone, GnRH or gonadotropines.

Topics: Adolescent; Adult; Age Factors; Female; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Hypogonadism; Infertility, Male; Kallmann Syndrome; Leptin; Male; Mutation; Olfaction Disorders; Prader-Willi Syndrome; Pregnancy; Puberty, Delayed; Receptors, Cell Surface; Receptors, Leptin; Spermatogenesis; Testosterone; Time Factors

Energy balance is closely related to reproductive function, wherein hypothalamic kisspeptin mediates regulation of the energy balance. However, the central mechanism of kisspeptin in the regulation of male reproductive function under different energy balance states is unclear. Here, high-fat diet (HFD) and exercise were used to change the energy balance to explore the role of leptin and inflammation in the regulation of kisspeptin and the hypothalamic-pituitary-testis (HPT) axis.. Four-week-old male C57BL/6 J mice were randomly assigned to a normal control group (n = 16) or an HFD (n = 49) group. After 10 weeks of HFD feeding, obese mice were randomly divided into obesity control (n = 16), obesity moderate-load exercise (n = 16), or obesity high-load exercise (n = 17) groups. The obesity moderate-load exercise and obesity high-load exercise groups performed exercise (swimming) for 120 min/day and 120 min × 2 times/day (6 h interval), 5 days/week for 8 weeks, respectively.. Compared to the mice in the normal group, in obese mice, the mRNA and protein expression of the leptin receptor, kiss, interleukin-10 (IL-10), and gonadotropin-releasing hormone (GnRH) decreased in the hypothalamus; serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels and sperm quality decreased; and serum leptin, estradiol, and tumor necrosis factor-α (TNF-α) levels and sperm apoptosis increased. Moderate- and high-load exercise effectively reduced body fat and serum leptin levels but had the opposite effects on the hypothalamus and serum IL-10 and TNF-α levels. Moderate-load exercise had anti-inflammatory effects accompanied by increased mRNA and protein expression of kiss and GnRH in the hypothalamus and increased serum FSH, LH, and testosterone levels and improved sperm quality. High-load exercise also promoted inflammation, with no significant effect on the mRNA and protein expression of kiss and GnRH in the hypothalamus, serum sex hormone level, or sperm quality. Moderate-load exercise improved leptin resistance and inflammation and reduced the inhibition of kisspeptin and the HPT axis in obese mice. The inflammatory response induced by high-load exercise may counteract the positive effect of improving leptin resistance on kisspeptin and HPT.. During changes in energy balance, leptin and inflammation jointly regulate kisspeptin expression on the HPT axis.

Topics: Animals; Energy Metabolism; Hypogonadism; Hypothalamus; Infertility, Male; Inflammation; Inflammation Mediators; Kisspeptins; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Reproduction; Signal Transduction

Adipokines could be a link between metabolic syndrome (MS) and infertility. While the association between circulating adipokines and fertility has been extensively studied in females, this relationship in males was less investigated, although some adipokines are detectable in seminal plasma (SP). The aim of this study was to determine adipokine levels in blood and SP and to assess the relationships between adipokines, MS and semen parameters in men from infertile couples.. Male partners of infertile couples referred to four medical French centers were enrolled in years 2013-2016.. Subjects (n = 160) aged 18-45 years were assessed for anthropometric, biochemical, sperm, and circulating hormonal parameters. Leptin, adiponectin, resistin, chemerin, visfatin, and IL-6 were measured in serum and SP.. Infertility duration was higher in men with than without MS. Adipokine concentrations were higher in blood than in SP, except for IL-6 and visfatin. The most striking result was the significant correlation observed between seminal IL-6 and spermatozoid concentration, progressive motility, and sperm vitality. Moreover, while men with MS exhibited an expected lower adiponectinemia, they displayed 2.1-fold higher adiponectin levels in SP than men without MS. Finally, logistic regression analysis showed that BMI, infertility duration, and adiponectin serum/SP ratio were independently associated with MS.. These results suggest an involvement of seminal adipokines to modulate fertility in men with MS and that seminal IL-6 could play a beneficial role on sperm functionality. Further mechanistic studies are necessary to investigate the precise roles of these adipokines in male reproduction.

Topics: Adipokines; Adolescent; Adult; Chemokines; Female; Humans; Infertility, Male; Interleukin-6; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Reproduction; Semen; Sperm Count; Sperm Motility; Spermatozoa; Young Adult

Topics: Humans; Infertility, Male; Leptin; Male; Obesity

The current evidence on the association between obesity-associated markers and semen quality, serum reproductive hormones and lipids remains inconsistent. In this study, we tested the hypothesis that, in infertile Chinese men, body mass index (BMI) negatively correlates with sperm concentration, serum total testosterone (TT), and high-density lipoprotein cholesterol (HDL-C). The relationship between other obesity-associated markers and semen quality parameters, serum reproductive hormones, lipids and leptin were also investigated.. 181 Chinese infertile men were recruited from September 2018 to September 2019. Their obesity-associated markers, semen parameters, and serum reproductive hormones, lipids and leptin were detected. Statistical analysis was performed to assess the relationship between obesity-associated markers and semen quality, serum reproductive hormones, lipids and leptin.. Statistically negative correlation was found between other obesity-associated markers (e.g. waist-to-hip ratio and waist-to-height ratio) and semen parameters (e.g. sperm concentration, ratio of progressive motility and ratio of non-progressive motility), while no significant correlation was found between BMI and semen quality, serum reproductive hormones, lipids and leptin. Ratio of morphologically normal sperm was negatively correlated with serum lipids including total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), leptin and seminal superoxide dismutase. Ratio of progressive sperm, sperm concentration and ratio of morphologically normal sperm exhibited significantly lower values in overweight group than normal group. Estradiol (E2) and E2/TT were significantly higher in obese group than normal group, while TT level was significantly lower in obese group than normal group. Univariate and multivariate analysis indicated that TC was significantly associated with BMI. Serum leptin concentration was positively correlated with seminal leptin concentration in overweight and obese groups.. No significant correlation was found between BMI and sperm concentration, serum TT and HDL-C, while other obesity-associated markers were found to negatively correlate with sperm concentration, ratio of progressive motility and ratio of non-progressive motility. Statistically significant correlations between serum reproductive hormones, lipids and leptin also existed in Chinese infertile men.

Topics: Adult; Asian People; Biomarkers; Body Mass Index; China; Cohort Studies; Gonadal Steroid Hormones; Humans; Infertility, Male; Leptin; Lipids; Male; Middle Aged; Obesity; Risk Factors; Semen Analysis; Young Adult

Varicocele is one of the most common causes of male infertility. Leptin that has a role in sperm motility may have a role of varicocele. We aimed to study the effect of varicocelectomy on the serum and seminal leptin in patients with asthenozoospermia and the correlation between leptin levels, sperm parameters and varicocele grade.. Thirty-six male patients with varicocele having isolated asthenozoospermia were included in this study. Thirty normal fertile controls were included. Semen analysis, serum and seminal leptin measurements were performed for all participants at baseline and for patients three months after varicocelectomy. Microsurgical varicocelectomy has been performed for patients.. Seminal and serum leptin levels were significantly higher in patients than controls. Seminal leptin was positively correlated with varicocele grade (. Varicocele is associated with higher levels of seminal and serum leptin especially in higher grads and this was correlated with negative effects on sperm motility. Leptin levels were significantly decreased after repair.

Topics: Asthenozoospermia; Humans; Infertility, Male; Leptin; Male; Sperm Motility; Varicocele

Male infertility is a major health problem worldwide. We investigated a possible association between leptin, obesity, hormonal interplay and male infertility. This cross-sectional study of 313 males (178 infertile and 135 fertile) was carried out in 2017. The subjects were categorised by body mass index (BMI) and body fat percentage (BF%) into normal weight, overweight and obese. Significantly higher levels of BMI and BF% (p-value < 0.001) and lower levels of FSH, LH, testosterone, and SHBG (p-value < 0.001) were found in infertile males. However, no significant difference was observed in leptin levels (p-value = 0.35). Leptin levels were significantly higher, and all the sex hormones were significantly lower (p-value < 0.001) in obese subjects, whereas according to BF% only leptin, FSH and SHBG were significantly different. Leptin showed a significant positive correlation with BMI and BF% (p < 0.001). A strong positive link to serum testosterone was found with age, FSH, and LH (p < 0.001) and a negative one with BMI and BF% (p < 0.001). In mutivariable anlaysis, after adjusting for the other covariates, a significant association between FSH and testosterone (p-value <0.001) was found. Serum leptin levels did not differ significantly in fertile and infertile groups, and no association was found with infertility. Furthermore, male obesity was found to be associated with infertility with the decrease in levels of sex hormones.

Topics: Adult; Body Mass Index; Cross-Sectional Studies; Follicle Stimulating Hormone; Humans; Infertility, Male; Leptin; Luteinizing Hormone; Male; Obesity; Overweight; Sex Hormone-Binding Globulin; Testosterone

Even though obesity surgery normalizes circulating testosterone concentrations in males with obesity-associated secondary hypogonadism, its impact on spermatogenesis remains controversial. We aimed to evaluate sperm characteristics in obese men after bariatric surgery as well as changes in reproductive hormones.. Twenty severely obese men (body mass index (BMI) ≥ 35 kg/m. After surgery, serum total testosterone, calculated free testosterone, inhibin B, and kisspeptin increased, whereas fasting insulin, HOMA-IR, and leptin concentrations decreased. Despite these improvements, sperm volume showed a small decrease after surgery, while the rest of sperm characteristics remained mostly unchanged. Abnormal sperm concentration persisted in 60% of the patients.. Sperm characteristics may not improve after bariatric surgery despite the beneficial changes of reproductive hormones.

Topics: Adult; Bariatric Surgery; Body Mass Index; Follow-Up Studies; Gonadal Steroid Hormones; Humans; Hypogonadism; Infertility, Male; Inhibins; Insulin; Leptin; Male; Middle Aged; Obesity, Morbid; Postoperative Period; Prognosis; Semen Analysis; Spermatozoa; Testosterone; Treatment Outcome

The aim of this study was to ascertain the associations between serum leptin levels and chronic epididymitis and semen parameters in patients with infertility.. A total of 846 patients who were diagnosed as primary infertility were enrolled and divided into four groups. The general information, blood lipids, reproductive hormones, and semen parameters were collected. Receiver operating characteristic (ROC) curves of leptin were plotted for diagnosis of the poor sperm quality. We used Student's t test and the chi-squared test to analyze their relationships and used logistic regression analysis to evaluate potential confounding factors.. Receiver operating characteristic curve revealed that leptin had better sensitivity and specificity at the concentration of 6.02 (0.565 and 0.917). Isolated epididymitis or elevated leptin had no effect on sperm concentration and sperm membrane function, but the combination of these conditions would reduce the concentration and normal morphology rate both (P = 0.002, P = 0.005). Epididymitis or elevated leptin can affect the motility of sperms, the former presented more significance (P = 0.000), and the co-existence would further reduce the sperm motility (P = 0.001).. Low sperm motility and sperm normal morphology were found to be associated with chronic epididymitis and high leptin. Simultaneously suffering from chronic epididymitis and high leptin could produce a more serious effect on sperm quality.

Topics: Adult; Epididymitis; Humans; Infertility, Male; Leptin; Lipids; Male; Semen; Semen Analysis; Spermatozoa; Young Adult

The obesity and its comorbidities, including resistance to leptin, impacts the reproductive function. Testes express leptin receptors in the germ cells and Leydig cells. Then, leptin-deficient animals are obese and infertile. We aimed to evaluate the structure and steroidogenic pathway of the testis of deficient leptin mice. Three months old male C57BL/6 mice (wild-type, WT) and deficient leptin (ob/ob) mice had their testes dissected and prepared for analyses. Compared to the WT group, the ob/ob group showed a greater body mass with smaller testes, and alterations in the germinative epithelium: fewer spermatogonia, spermatocytes, and spermatids. The Sertoli cells and the germ cells showed condensed nuclei and nuclear fragmentation indicating cell death, in agreement with a low expression of the proliferating cell nuclear antigen and a high expression of Caspase3. In the ob/ob group, the sperm was absent in the seminiferous tubules, and the steroidogenic pathway was compromised (low 3Beta hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein). Further, all hormone receptors involved in the testicular function were down expressed (androgen, estrogen, follicle-stimulating, luteinizing, aromatase, and nicotinamide adenine dinucleotide phosphate). In conclusion, the findings indicate significant morphological, hormonal and enzymatic changes in the testis of the ob/ob mice. The shifts in the enzymatic steroidogenic pathway and the enzymes related to spermatic activity support the insights about the failures in the fertility of these animals. The study provides new evidence and contributes to the understanding of how the lack of leptin and obesity might negatively modulate the testicular function leading to infertility.

Topics: Animals; Blotting, Western; Body Size; Caspase 3; Fluorescent Antibody Technique; Gene Deletion; Gene Expression Regulation; Infertility, Male; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Phosphoproteins; Polymerase Chain Reaction; Proliferating Cell Nuclear Antigen; Testis

The aim of this study was to examine whether there is an association among genetic variability in leptin (LEP) and leptin receptor (LEPR) genes and male infertility. We performed a case-control study and were searching for an association between polymorphisms of LEP and LEPR genes and male infertility. The study group consisted of 317 patients with idiopathic infertility and a control group of 241 fertile men from Slovenia. Four single nucleotide polymorphisms (SNPs) in LEP gene and four single nucleotide polymorphisms (SNPs) in LEPR gene were chosen and genotyped. Statistically significant SNP was further validated in additional 255 infertile patients and 168 controls from Serbia and Macedonia. In the Slovenian population, we found a statistically significant difference in genotype distribution for rs10244329 polymorphism in LEP gene (recessive genotype model, p value = 0.048). The trend toward statistically significant difference in genotype distribution for rs10244329 polymorphism was confirmed in the Serbian and Macedonian populations (p value = 0.07). Our data suggest that genetic variability in the LEP gene might be associated with male infertility warranting further confirmation and mechanistic investigations.

Topics: Adult; Alleles; Case-Control Studies; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Infertility, Male; Leptin; Male; Middle Aged; Polymorphism, Single Nucleotide; Receptors, Leptin; Republic of North Macedonia; Risk Factors; Serbia; Sperm Count

The association of leptin (LEP) -2548G/A and/or leptin receptor (LEPR) Gln223Arg polymorphisms with male infertility and plasma FSH, LH, and testosterone (T) levels was examined. The genotypes and allele frequency distributions of LEP -2548G/A and LEPR Gln223Arg polymorphisms were investigated in 150 fertile and 150 infertile men by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Also, plasma levels of FSH, LH, and T were measured using commercial ELISA kits. Frequencies of AA, AG and GG genotypes of LEP-2548G/A polymorphism were statistically different in fertile and infertile men (p=0.012). The AG genotype showed a protective effect which could decrease risk of male infertility about 3 fold (p = 0.004). We did not observe any differences in frequencies of LEPR Gln223Arg alleles and genotypes between groups (p > 0.05). Sperm counts from infertile men with the AG and GG genotypes of the LEP polymorphism were significantly higher than AA genotype (p<0.05). Moreover, infertile men who carried the RR genotype of LEPR showed a statistically higher percentage of sperm with progressive motility than individuals with other genotypes (p = 0.004). There was no correlation between different combinations of LEP and LEPR genotypes and LH, FSH, and T levels (p > 0.05). Our study suggests that the LEP -2548G/A polymorphism may play a role in male fertility and the AG genotype may have a protective effect through increasing sperm counts. The distribution of genotypes of LEP -2548G/A polymorphism are different in fertile and infertile males and may be a useful tool in evaluation of male infertility.. LEP: leptin; LEPR: leptin receptor; T: testosterone; FSH: follicle-stimulating hormone; LH: luteinizing hormone.

Topics: Adult; Biomarkers; Case-Control Studies; Fertility; Follicle Stimulating Hormone, Human; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Heterozygote; Homozygote; Humans; Infertility, Male; Leptin; Luteinizing Hormone; Male; Phenotype; Polymorphism, Single Nucleotide; Protective Factors; Receptors, Leptin; Risk Factors; Sperm Count; Testosterone

There is an ever increasing body of evidence that demonstrates that paternal over-nutrition prior to conception programs impaired metabolic health in offspring. Here we examined whether paternal under-nutrition can also program impaired health in offspring and if any detrimental health outcomes in offspring could be prevented by micronutrient supplementation (vitamins and antioxidants). We discovered that restricting the food intake of male rodents reduced their body weight, fertility, increased sperm oxidative DNA lesions and reduced global sperm methylation. Under-nourished males then sired offspring with reduced postnatal weight and growth but somewhat paradoxically increased adiposity and dyslipidaemia, despite being fed standard chow. Paternal vitamin/antioxidant food fortification during under-nutrition not only normalised founder oxidative sperm DNA lesions but also prevented early growth restriction, fat accumulation and dyslipidaemia in offspring. This demonstrates that paternal under-nutrition reduces postnatal growth but increases the risk of obesity and metabolic disease in the next generation and that micronutrient supplementation during this period of under-nutrition is capable of restoring offspring metabolic health.

Topics: Adiposity; Animals; Antioxidants; Body Composition; Embryonic Development; Female; Food, Fortified; Founder Effect; Infertility, Male; Insulin; Leptin; Lipids; Male; Malnutrition; Metabolic Syndrome; Mice, Inbred C57BL; Paternal Inheritance; Reactive Oxygen Species; Sperm Count; Sperm Motility

The aim of this study is to compare serum and seminal level of leptin in the context of infertility in men according to BMI. We also investigated the possible correlation of circulating level of leptin with fertility indices.. This case-control study was conducted on 193 men who consecutively attended a referral outpatient infertility clinic of Shariati Hospital. The leptin level in serum and seminal plasma were quantified by enzymelinked immunosorbent assay (ELISA) in fertile men (n = 95) and infertile men (n = 98). All participant were ageand BMI-matched. Semen was also analyzed in terms of volume, sperm concentration (106/mL), motility (%), and morphology in all subjects prior to study. Based on body mass index (BMI) value, all participants were divided into three groups; lean, body mass index (BMI) 19 - 24.99kg/m2, overweight, BMI 25 - 29.99 kg/m2, and obese BMI ≥ 30 kg/m2.. Fertile and infertile men were significantly compatible regarding sperm concentration; however, we found no significant difference in case of the leptin level in serum and semen between the two studied groups (p-value = 0.5 and p-value = 0.1, respectively). In the infertile group, serum leptin level was significantly correlated with BMI (r = -0.291; p = 0.004 for the fertile group). Moreover, there was an inverse correlation between serum leptin level and sperm motility (r = -0.241; p = 0.014) in infertile men. Interestingly, among the infertile group, we observed an augmented serum level of leptin in obese men in comparison with lean (p = 0.009) and overweight (p = 0.07) individuals.. Our findings along with other studies support this concept that increased BMI is of clinical relevance in the context of infertility in men since our data revealed an inverse correlation between seminal leptin level and BMI in infertile men. Specifically, alteration in serum level of leptin was obviously different in infertile men in terms of overweight and obesity. However, more studies are required to unravel obscure issues in this regard.

Topics: Adult; Biomarkers; Body Mass Index; Case-Control Studies; Fertility; Humans; Infertility, Male; Leptin; Male; Obesity; Semen; Sperm Count; Sperm Motility

The rate of obesity among men of reproductive age has tripled in the last three decades. Previously, we demonstrated that paternal obesity resulted in impaired preimplantation developmental kinetics, compromised post-compaction metabolism and decreased blastocyst cell number when embryos were generated in vivo. Subsequently, using in vitro fertilization we found embryos of obese males to have altered metabolism before compaction, reduced inner cell mass cell number and retarded fetal development--the difference between these two studies being the method of embryo generation and the presence or absence of seminal plasma, respectively. Here, we hypothesize that both sperm and seminal plasma are affected by obesity, compromising embryogenesis and pregnancy health in a cumulative manner. Epididymal sperm and seminal vesicle fluid were collected from normal and obese C57BL/6 mice. RNA and DNA were extracted from spermatozoa for qPCR and global methylation analysis, respectively. Proteomic (Luminex) and metabolomic (GC-MS) techniques were employed to analyse the composition of seminal vesicle fluid. Nuclear encoded cytochrome c oxidase subunit IV isoform 1 (Cox4i1) of the terminal enzyme in the mitochondrial respiratory chain demonstrated significantly increased RNA levels in the sperm of obese males (P< 0.05). Quantitative seminal plasma analysis identified significant changes in levels of the hormones insulin, leptin and estradiol between normal and obese males (P < 0.05). Further, the metabolite composition of seminal vesicle fluid was significantly affected by obesity. Consequently, this study has determined that obesity affects both sperm and seminal plasma composition. The interaction between sperm and seminal plasma warrants further analysis.

Topics: Animals; Diet, High-Fat; Electron Transport Complex IV; Estradiol; Gene Expression Regulation, Developmental; Infertility, Male; Insulin; Leptin; Male; Mice, Inbred C57BL; Obesity; Protein Subunits; Random Allocation; RNA, Messenger; Semen; Seminal Plasma Proteins; Sperm Count; Sperm Motility; Spermatozoa; Up-Regulation

The present study was designed to evaluate the relationship between serum leptin and infertility in obese young and old men and women. The groups of infertile obese men (n=66) and women (n=30) compared with control obese fertile men (n=60) and women (n=30) with same ages to find the contribution of serum leptin level in causation of fertility. The results revealed that serum leptin were significantly raised in infertile male and female with p<0.001. BMI was also found to be significantly higher (p<0.001) in infertile men and women. Moreover a strong positive correlation was found between BMI and leptin level, and serum leptin and age in both fertile and infertile men and women. The values of correlation coefficients between serum leptin and BMI, and serum leptin and age are statistically significant (r=0.3-0.6, p<0.01-p<0.05). This study has concluded that obesity is associated with infertility in men and women. Sex hormonal imbalance may also be associated BMI and serum leptin in infertility. However further studies are required to determine the exact match by which enhanced BMI and serum leptin levels to female and male infertility.

Topics: Adult; Body Mass Index; Case-Control Studies; Female; Humans; Infertility, Female; Infertility, Male; Leptin; Male; Middle Aged; Obesity

An increased global prevalence of obesity coincides with an apparent decline in male sperm quality and a possible association between these pathologies has been suggested. In this study, we examined the effects of obesity on sperm chromatin integrity using two mouse models of obesity. In one group of mice, obesity was induced by a high-fat diet (HFD) (diet-induced obesity; DIO model), whereas in the other group, leptin deficiency was used to study the effects of obesity independently of the influence of dietary factors. Sperm chromatin integrity is recognized as an important measure of male infertility, and was analysed by the sperm chromatin structure assay. We found increased sperm DNA fragmentation in both groups of obese mice compared to lean mice, whereas the percentage of immature spermatozoa was not increased by obesity. The DIO model reflects the human condition more closely than the leptin-deficient model and was therefore selected for examination of the transcriptional response of a selection of marker genes in the testis by quantitative real-time PCR. The analysis of transcript levels of the selected testicular marker genes showed moderate, but significant, up-regulation of the Cyp2e1, Cyp19a1, Tnf and Pparg genes in DIO mice compared to lean mice. In conclusion, a clear positive correlation between body mass index and sperm DNA fragmentation was found in two mouse models of obesity. However, the variability in sperm DNA fragmentation within the two groups of obese animals was high. The observed changes in the transcript level of the marker genes suggest that there may be a local response in testicular cells to the HFD regimen with a potential impact on intratesticular signalling and spermatogenesis.

Topics: Animals; Aromatase; Body Mass Index; Chromatin; Cytochrome P-450 CYP2E1; Diet, High-Fat; DNA Fragmentation; Gene Expression; Infertility, Male; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; PPAR gamma; Semen Analysis; Spermatozoa; Tumor Necrosis Factors; Up-Regulation

Type 1 diabetes is associated with subfertility in humans. The current treatment for type 1 diabetes, insulin monotherapy, is suboptimal to fully stabilize glycemia, potentially leading to this subfertility. Recent work has demonstrated that treatment with the energy-regulating hormone leptin, alone or in combination with insulin, can more effectively control glycemia in mouse models of type 1 diabetes. Here, we sought to determine whether the fertility defects in a type 1 diabetic mouse model, the Akita mouse, can be rescued with leptin monotherapy in the absence of any exogenous insulin. Akita homozygous mice treated with leptin alone had a larger total body size, testes, and seminal vesicles than their untreated siblings. Leptin treatment prevented testicular degeneration and rescued sperm motility to wild-type levels. Furthermore, sperm obtained from leptin-treated mice could successfully fertilize ooctyes in vitro. Despite completely rescuing spermatogenesis, the critical reproductive hormones LH and testosterone were only modestly higher than in untreated mice, indicating that a minimum threshold of these hormones must be met to maintain spermatogenesis. Cumulatively, these findings implicate the importance of leptin in maintaining fertility and support the use of leptin therapy in the treatment of type 1 diabetes.

Topics: Adiposity; Animals; Atrophy; Diabetes Mellitus, Type 1; Disease Models, Animal; Genetic Carrier Screening; Homozygote; Infertility, Male; Leptin; Luteinizing Hormone; Male; Mice; Spermatogenesis; Testosterone

Obesity appears to be associated with male reproductive dysfunction and infertility, although this has been inconsistent and inconclusive. Insulin and leptin are known mediators and modulators of the hypothalamus-pituitary-testes axis, contributing to the regulation of male reproductive potential and overall wellbeing. These hormones are also present in semen influencing sperm functions. Although abdominal obesity is closely associated with insulin resistance (hyperinsulinaemia), hyperleptinaemia and glucose dysfunction, changes in seminal plasma concentrations of insulin, leptin and glucose in obese males has not previously been investigated.. This small case controlled study assessed serum and seminal concentrations of insulin, leptin and glucose in obese (BMI > =30; n = 23) and non-obese (BMI < 30; n = 19) males. Following a detailed medical history and examination, participants meeting the inclusion criteria were entered for data analysis. Body parameters such as BMI, waist and hip circumference and the waist hip ratio were measured. Serum and semen samples were collected and assayed for insulin, leptin and glucose. Semen samples also underwent a standard semen analysis, with sperm mitochondrial membrane potential (MMP) and DNA fragmentation (DF).. Obesity was associated with increased serum and seminal insulin and leptin, with no significant difference in seminal glucose. Serum and seminal concentrations of insulin and leptin were positively correlated. Furthermore, obesity was associated with decreased sperm concentration, sperm vitality and increased MMP and DF, with a non-significant impact on motility and morphology.. Hyperinsulinaemia and hyperleptinaemia are associated with increased seminal insulin and leptin concentrations, which may negatively impact male reproductive function in obesity. Insulin was also found to be highly concentrated in the seminal plasma of both groups. This data will contribute to the contradictive information available in the literature on the impact of obesity and male reproduction.

Topics: Adult; Body Mass Index; Case-Control Studies; Cohort Studies; DNA Fragmentation; Humans; Hyperinsulinism; Infertility, Male; Insulin; Leptin; Male; Membrane Potential, Mitochondrial; Middle Aged; Obesity; Pilot Projects; Semen; Semen Analysis; South Africa; Up-Regulation; Young Adult

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous autosomal recessive disorder characterized by obesity, retinal degeneration, polydactyly, hypogenitalism and renal defects. Recent findings have associated the etiology of the disease with cilia, and BBS proteins have been implicated in trafficking various ciliary cargo proteins. To date, 17 different genes have been reported for BBS among which BBS1 is the most common cause of the disease followed by BBS10, and BBS4. A murine model of Bbs4 is known to phenocopy most of the human BBS phenotypes, and it is being used as a BBS disease model. To better understand the in vivo localization, cellular function, and interaction of BBS4 with other proteins, we generated a transgenic BBS4 mouse expressing the human BBS4 gene under control of the beta actin promoter. The transgene is expressed in various tissues including brain, eye, testis, heart, kidney, and adipose tissue. These mice were further bred to express the transgene in Bbs4 null mice, and their phenotype was characterized. Here we report that despite tissue specific variable expression of the transgene, human BBS4 was able to complement the deficiency of Bbs4 and rescue all the BBS phenotypes in the Bbs4 null mice. These results provide an encouraging prospective for gene therapy for BBS related phenotypes and potentially for other ciliopathies.

Topics: Animals; Bardet-Biedl Syndrome; Cilia; Disease Models, Animal; Female; Gene Expression; Genotype; Humans; Hydrocephalus; Infertility, Male; Kidney; Leptin; Male; Mice; Mice, Knockout; Mice, Transgenic; Microtubule-Associated Proteins; Obesity; Phenotype; Proteins; Retinal Diseases; Sympathetic Nervous System; Testis; Transgenes

To investigate whether ghrelin signaling is involved in the pathogenesis of male factor infertility induced by leptin deficiency.. Experimental study.. University academic medical center.. Ten-week-old C57BL/6J mice and ob/ob mice.. Western blotting, (quantitative) reverse transcription-polymerase chain reaction (qRT-PCR), immunohistochemistry, and in situ end labeling of fragmented DNA.. Expression levels of ghrelin and its functional receptor growth hormone (GH) secretagogue receptor 1a (GHS-R1α) were examined by Western blotting and immunohistochemistry. Ob/ob mice were injected IP with specific GHS-R1α antagonist, and thereafter germ cell apoptosis and steroidogenic capability were assessed by TUNEL assay, (q) RT-PCR, and radioimmunoassay.. Expression of GHS-R1α and its endogenous ligand ghrelin was both up-regulated in ob/ob testis. Inhibition of the ghrelin pathway restored androgen synthesis, reduced germ cell apoptosis, and thereby resulted in improved sperm production in ob/ob mice.. Ghrelin, as an antagonistic partner of leptin in the endocrinic/paracrine circuit, may be involved in the pathogenesis of male factor infertility induced by leptin deficiency.

Topics: Androgens; Animals; Apoptosis; Fertility; Ghrelin; Infertility, Male; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Phenotype; Receptors, Ghrelin; Signal Transduction; Testis; Testosterone; Up-Regulation

Obesity is rapidly becoming a worldwide epidemic that affects children and adults. Some studies have shown a relationship between obesity and infertility, but until now it remains controversial. Thus, the aim of the present study was to investigate the effect of high-fat diet-induced obesity on male reproductive parameters.. In a first experiment, male Wistar rats were fed a high-fat diet (HFD) or standard chow (SD) for 15, 30 or 45 weeks, after which they were evaluated by adiposity index, serum leptin levels, reproductive organ weights and sperm counts. In a second experiment, rats received HFD or SD only for 15 weeks, long enough to cause obesity. Sexual hormones and sexual behavior were evaluated in these animals, as well as fertility after natural mating. Another group of rats was submitted to motility analysis and fertility evaluation after in utero insemination.. After 15, 30 or 45 weeks, HFD-fed animals presented significant increases in obesity index and serum leptin levels. Reproductive organ weights and sperm counts in the testis and epididymis were similar between the two groups at all timepoints studied. Sexual behavior was not altered by the diet regimen, and HFD fertility after natural mating was also similar to SD-fed animals. Intergroup testosterone levels were also comparable, but estradiol levels were increased in HFD rats. Furthermore, sperm quality was reduced in HFD animals as evidenced by their decreased percentage of sperm with progressive movement. This altered motility parameter was followed by a trend toward reduction in fertility potential after artificial in utero insemination.. The results reported herein showed that obesity can affect sperm quality, by reducing sperm motility, without affecting other sperm parameters. The low sperm quality caused a slight reduction in fertility potential, showing that obesity may lead to impairment in male fertility.

Topics: Animals; Dietary Fats; Estradiol; Infertility, Male; Leptin; Male; Obesity; Rats; Rats, Wistar; Sexual Behavior, Animal; Sperm Motility; Testosterone

To determine the leptin levels in the serum of normal, subfertile and infertile men.. Analytical study.. Department of Animal Sciences Quaid-e-Azam University, Islamabad, National Institute of Health (NIH), Islamabad and Dr. Salma and Kafeel Medical Centre, Islamabad, from April to December 2009.. Serum leptin levels hormonal concentrations (LH, FSH and testosterone) were determined by EIA in 154 males including 24 (15.58%) fertile, 19 (12.34%) polyzoospermic (PZs), 26 (16.88%) teratozoospermic (TZs), 27 (17.53%) astheno-teratozoospermic (ATZs), 18 (11.69%) oligozoospermic (OZs), 18 (11.69%) oligo-astheno-teratozoospermic (OATZs), 11 (7.14%) obstructive azoospermic (OBST-AZOOs) and 11 (7.14%) non-obstructive azoospermic (NON-OBSTAZOOs). BMI was also determined, divided into groups of greater than 24. Hormonal concentrations were compared by ANOVA and correlation was performed by using Graph pad prism version 5.. Significantly high levels of leptin concentrations were found in fertile (p < 0.001) as well as TZs, PZs, OZs, ATZs, (p < 0.001), OATZs (p < 0.01) and NON-OBST-AZOOs (p < 0.05) male subjects with BMI > 24 compared to fertile and infertile male patients with BMI < 24. Serum testosterone concentrations were significantly lower in PZs, OATZs, OZs, NON-OBST-AZOOs male patients with BMI < 24 compared to PZs (p < 0.05), OATZs, OZs (p < 0.01), OBST-AZOOs (p < 0.001) male patients with BMI > 24. Leptin showed a significant positive correlation with LH (p < 0.01) and FSH (p < 0.002) and a significant negative correlation with testosterone (p < 0.001).. Abnormal leptin level was significantly associated with fertility problems in males. Providing a link between leptin and reproduction factors contributing in control of testosterone and gonadotropins secretion in many aspects depending on fertility status in male subjects. BMI appears to have significant association with serum leptin levels.

Topics: Adult; Biomarkers; Fertility; Humans; Infertility, Male; Leptin; Male; Middle Aged; Oligospermia; Testosterone; Young Adult

The prevalence of human obesity and related chronic disorders such as diabetes, cardiovascular diseases, and cancer is rapidly increasing. Human studies have shown a direct relationship between obesity and infertility. The objective of the current work was to examine the effect of diet-induced obesity on male fertility and the effect of obesity on susceptibility to chemical-induced reproductive toxicity. From 5 to 30 wk of age, genetically intact male C57Bl/6J mice were fed a normal diet or one in which 60% of the kilocalories were from lard. Obese mice exhibited significant differences in the mRNA of several genes within the testes in comparison to lean males. Pparg was increased 2.2-fold, whereas Crem, Sh2b1, Dhh, Igf1, and Lepr were decreased 6.7, 1.4, 3.2, 1.6, and 7.2-fold, respectively. The fertility of male mice was compared through mating with control females. Acrylamide (AA)-induced reproductive toxicity was assessed in obese or lean males treated with water or 25 mg AA kg(-1) day(-1) via gavage for 5 days and then mated to control females. Percent body fat and weight were significantly increased in mice fed a high-fat vs. a normal diet. Obesity resulted in significant reduction in plugs and pregnancies of control females partnered with obese vs. lean males. Serum leptin and insulin levels were each approximately 5-fold higher in obese vs. age-matched lean mice. Sperm from obese males exhibited decreased motility and reduced hyperactivated progression vs. lean mice. Treatment with AA exacerbated male infertility of obese and lean mice; however, this effect was more pronounced in obese mice. Further, females partnered with AA-treated obese mice exhibited a further decrease in the percentage of live fetuses, whereas the percentage of resorptions increased. This work demonstrated that diet-induced obesity in mice caused a significant reduction in male fertility and exacerbated AA-induced reproductive toxicity and germ cell mutagenicity.

Topics: Acrylamide; Adipose Tissue; Animals; Blood Glucose; Body Weight; Cholesterol; Copulation; Cytochrome P-450 CYP2E1; Dietary Fats; Female; Germ-Line Mutation; Infertility, Male; Insulin; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Paternal Exposure; Pregnancy; Pregnancy Rate; Reverse Transcriptase Polymerase Chain Reaction; Sperm Count; Sperm Motility; Testis; Triglycerides

Adiponectin is an adipokine, present in the circulation in comparatively high concentrations and different molecular weight isoforms. For the first time, the distribution of these isoforms in serum and follicular fluid (FF) and their usefulness as biological markers for infertility investigations was studied.. In vitro study.. University based hospital.. Fifty-four women undergoing intracytoplasmic sperm injection (ICSI).. Oocytes were retrieved, fertilized in vitro using ICSI, and the resulting embryos transferred. Serum was collected immediately prior to oocyte retrieval. Adiponectin isoforms (high molecular weight (HMW), medium and low molecular weight) were determined in serum and FF. Total adiponectin and the different isoform levels were compared with leptin and ovarian steroid concentrations.. Adiponectin isoforms in serum and FF.. Adiponectin isoform distribution differed between serum and FF; the HMW fraction made up half of all adiponectin in the serum but only 23.3% in the FF. Total and HMW adiponectin in both serum and FF correlated negatively with the body mass index and the concentration of leptin. No correlations were observed for total adiponectin or its isoforms with estradiol, progesterone, anti-Mullerian hormone, inhibin B, or the total follicle stimulating hormone (FSH) dose administered during the ovarian stimulation phase.. This study shows for the first time that adiponectin isoform distribution varies between the serum and FF compartments in gonadotropin stimulated patients. A trend towards higher HMW adiponectin serum levels in successful ICSI cycles compared to implantation failures was observed; studies with larger patient groups are required to confirm this observation.

Topics: Adiponectin; Adult; Anti-Mullerian Hormone; Biomarkers; Embryo Implantation; Estradiol; Female; Fertilization in Vitro; Follicular Fluid; Humans; Infertility, Male; Inhibins; Leptin; Male; Oocyte Retrieval; Ovulation Induction; Progesterone; Protein Isoforms; Sperm Injections, Intracytoplasmic

Obstructive sleep apnea disease (OSA) is associated with a myriad of endocrine adverse effects. Changes in the serum prolactin (PRL) secretion in OSA are thought to be related to the hypoxic stress and subsequently to result in reversible changes with effective continuous positive airway pressure (CPAP) therapy. Due to current disagreements on this topic, we investigated the effect of CPAP therapy on the serum PRL in patients with OSA, using the most accurate CPAP compliance assessment to date. Fourteen adults were recruited from those scheduled at the Salem Veterans Affairs Medical Center for a diagnostic polysomnogram (PSG). Fasting serum PRL, estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (Test), glucose, cortisol (Cor), and leptin levels were measured at 7 a.m., the morning after PSG, and again in ten of these patients, after 11-39 months of CPAP therapy. Compliance data, for both short-term (mean, 34 days) and long-term follow-up (mean, 304 days), were downloaded.. Except PRL, no other hormone's serum level, including that of FSH, LH, Test, Cor, and Leptin, has changed significantly after the CPAP therapy.. CPAP therapy is associated with a significant decrease in serum PRL levels.

Topics: Adult; Aged; Blood Glucose; Continuous Positive Airway Pressure; Estradiol; Follicle Stimulating Hormone; Follow-Up Studies; Humans; Hydrocortisone; Infertility, Male; Leptin; Luteinizing Hormone; Male; Middle Aged; Patient Compliance; Prolactin; Sleep Apnea Syndromes; Testosterone

In the present study, differences in leptin levels between different groups of male patients presenting with infertility problems and possible correlations between leptin levels and clinical, spermiological, histological and hormonal characteristics were examined. Two hundred and ten male partners from infertile couples were included in the study. Based on clinical examination, spermiogram and testicular histology results, patients were divided into four groups: 42 men with non-obstructive azoospermia, 15 men with obstructive azoospermia, 68 men with oligoasthenoteratozoospermia and 85 men with normozoospermia. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, testosterone, sex hormone binding globulin (SHBG) and leptin were measured. After adjustment for body mass index, there was a negative correlation between serum levels of leptin and inhibin B, total testosterone and SHBG (r = -0.189, p = 0.009, r = -0.250, p = 0.001 and r =-0.221, p = 0.003 respectively) but there was no correlation between leptin and classical sperm characteristics. Our results therefore demonstrate a link between leptin and testicular function, independently of FSH and LH, possibly involving testosterone and SHBG through a regulation of Leydig cell function.

Topics: Humans; Infertility, Male; Inhibins; Leptin; Male; Sex Hormone-Binding Globulin; Spermatozoa; Testosterone

The aim of our study was to investigate the relationships between the expression of leptin, leptin receptor in the testis and spermatogenesis, and testosterone (T) concentration in infertile men. Testicular tissue samples were collected from the testes of five fertile volunteers, eight patients with obstructive azoospermia (OA), six patients with Sertoli cell-only syndrome (SCO) and 32 oligospermic patients with varicocele testis. In testicular tissue, leptin and leptin receptor were identified by staining with polyclonal antibodies. Serum follicle stimulating hormone, lutenising hormone (LH), and T were determined by chemiluminescence assays. Leptin was expressed on germ cells, mainly on spermatocytes. The ratio of immunostained germ cells to total germ cells was inversely correlated with the concentration of T (r = -0.32, P = 0.01), sperm concentration (r = -0.51, P = 0.002) and Johnsen's score (r = -0.44,P = 0.005). In contrast, leptin receptor immunostained cells were found in the interstitium, primarily in Leydig cells. Leptin receptor expression on Leydig cells was inversely correlated with serum T concentration (r = -0.50, P < 0.001). The dysfunction of spermatogenesis is associated with an increase in leptin and leptin receptor expression in the testis.

Topics: Adult; Gene Expression; Humans; Infertility, Male; Leptin; Leydig Cells; Male; Middle Aged; Oligospermia; Receptors, Cell Surface; Receptors, Leptin; Testis; Testosterone; Varicocele

Leptin is an adipocyte-secreted protein that participates in the regulation of energy homeostasis. Eighty men were investigated; fertile normozoospermia as a control (n = 30) and infertile oligozoospermia (n = 50). The patients underwent estimation of body weight (kg), height (cm), calculation of body mass index (BMI), semen analysis, serum leptin and testosterone hormones. Mean body weight was significantly higher in infertile oligozoospermia compared with controls. Mean height, BMI and serum testosterone levels showed nonsignificant differences between the two groups. Infertile oligozoospermia had significantly higher mean serum leptin level than controls (mean +/- SD; 6.88 +/- 8.65, 16.3 +/- 13.98 ng ml(-1), P < 0.01). Serum leptin demonstrated significant positive correlation with age, body weight, BMI and significant inverse correlation with serum testosterone. It had nonsignificant correlation with the height and sperm concentration. These results are suggestive of a link between the adipocyte derived hormone, leptin and male reproduction.

Topics: Adult; Age Factors; Body Mass Index; Body Weight; Case-Control Studies; Humans; Infertility, Male; Leptin; Male; Middle Aged; Oligospermia; Prospective Studies; Testosterone

Signal transducer and activator of transcription (STAT)3 is widely expressed in the CNS during development and adulthood. STAT3 has been implicated in the control of neuron/glial differentiation and leptin-mediated energy homeostasis, but the physiological role and degree of involvement of STAT3 in these processes is not defined and controversial because of the lack of a direct genetic model. To address this, we created mice with a neural-specific disruption of STAT3 (STAT3(N-/-)). Surprisingly, homozygous mutants were born at the expected Mendelian ratio without apparent developmental abnormalities but susceptible to neonatal lethality. Mutants that survived the neonatal period were hyperphagic, obese, diabetic, and infertile. Administering a melanocortin-3/4 receptor agonist abrogated the hyperphagia and hypothalamic immunohistochemistry showed a marked reduction in proopiomelanocortin with an increase in neuropeptide Y and agouti-related protein. Mutants had reduced energy expenditure and became hypothermic after fasting or cold stress. STAT3(N-/-) mice are hyperleptinemic, suggesting a leptin-resistant condition. Concomitant with neuroendocrine defects such as decreased linear growth and infertility with accompanying increased corticosterone levels, this CNS knockout recapitulates the unique phenotype of db/db and ob/ob obese models and distinguishes them from other genetic models of obesity. Thus, STAT3 in the CNS plays essential roles in the regulation of energy homeostasis and reproduction.

Topics: Acute-Phase Proteins; Adipose Tissue, Brown; Animals; Body Temperature Regulation; Corticosterone; Diabetes Mellitus; DNA-Binding Proteins; Female; Infertility, Female; Infertility, Male; Intermediate Filament Proteins; Kinetics; Leptin; Male; Mice; Mice, Knockout; Mice, Transgenic; Nerve Tissue Proteins; Nestin; Obesity; Rats; STAT3 Transcription Factor; Time Factors; Trans-Activators

Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are two closely related peptides that bind two homologous G protein-coupled receptors, VIP/PACAP receptor 1 (VPAC1R) and VIP/PACAP receptor II (VPAC2R), with equally high affinity. Recent reports suggest that VPAC2R plays a role in circadian rhythm and T cell functions. To further elucidate the functional activities of VPAC2R, we generated VPAC2R-deficient mice by deleting exons VIII-X of the VPAC2R gene. The VPAC2R-deficient mice showed retarded growth and had reduced serum IGF-I levels compared with gender-matched, wild-type siblings. The mutant mice appeared healthy and fertile at a young adult age. However, older male mutant mice exhibited diffuse seminiferous tubular degeneration with hypospermia and reduced fertility rate. The mutant mice appeared to have an increase in insulin sensitivity. VPAC2R-deficient mice had increased lean mass and decreased fat mass with reduced serum leptin levels. Indirect calorimetry experiments showed that the respiratory quotient values immediately following the transition into the dark cycle were significantly higher in male knockout mice for about 4 h. Additionally, male and female VPAC2R-deficient mice presented an increased basal metabolic rate (23% and 10%, respectively) compared with their wild-type siblings. Our results suggest that VPAC2R plays an important role in growth, basal energy expenditure, and male reproductive functions.

Topics: Amino Acid Sequence; Animals; Basal Metabolism; Body Composition; Female; Growth; Growth Disorders; Infertility, Male; Insulin; Insulin-Like Growth Factor I; Leptin; Male; Mice; Mice, Knockout; Molecular Sequence Data; Receptors, Vasoactive Intestinal Peptide; Receptors, Vasoactive Intestinal Peptide, Type II; Reference Values; Seminiferous Tubules; Sex Characteristics; Sperm Count

Topics: Adult; Follicle Stimulating Hormone; Humans; Infertility, Male; Leptin; Luteinizing Hormone; Male; Oligospermia; Prolactin; Reference Values; Testosterone

Fetal alcohol syndrome usually implies effects on the offspring of maternal EtOH consumption during gestation, with fewer reports addressing the impact of paternal exposure on the progeny. One previous report has dealt with the impact of EtOH exposure on peripubertal male rats as a model of teenage drinking and the deleterious effects on the offspring. We report here findings examining the effect of 2 mo of EtOH feeding on male animals as they progressed through puberty on their ability to impregnate EtOH-naive female rats and characteristics of the subsequent litters. The EtOH-imbibing fathers weighed significantly less than pairfed controls and animals ingesting a non-EtOH liquid diet ad libitum. Nevertheless, they were able to mate successfully, although fecundity was significantly reduced. The number of successful pregnancies, defined as carried to term, was diminished from 92% in controls to 75% in EtOH-fed animals (p < 0.05). There was increased paternal testicular oxidative injury demonstrated by enhanced lipid peroxidation, protein oxidation, and decreased ratio of reduced to oxidized glutathione. The litter size of the EtOH-exposed males was reduced by 46%. The average litter size was 12.4+/-1.5 pups/litter in ad libitum animals, virtually identical to the 12.5+/-0.6 pups/litter in the pair fed controls. This is in sharp contrast to the 6.7+/-0.1 pups/litter from the paternal EtOH matings (p < 0.001). There was an increase in the average individual weight of pup offspring of paternally EtOH-exposed animals (p < 0.01 vs pair-fed controls and p < 0.05 vs ad libitum). Curiously, the male-to-female pup ratio was altered with a higher preponderance of male offspring from EtOH-fed fathers. There were no gross malformations noted among the pups. Insulin-like growth factor-1 levels in the pups at 10 d of age were unaltered between the groups. However, leptin was significantly elevated in the EtOH offspring. It appears that chronic EtOH exposure in the peripubertal fathers subsequently decreases fecundity and that this may be mediated by testicular oxidative injury, perhaps leading to accelerated germ cell apoptosis.

Topics: Animals; Animals, Newborn; Ethanol; Fathers; Female; Glutathione; Infertility, Male; Insulin-Like Growth Factor I; Leptin; Lipid Peroxidation; Litter Size; Male; Oxidation-Reduction; Oxidative Stress; Pregnancy; Rats; Rats, Sprague-Dawley; Sexual Maturation; Testis