phytoestrogens and Weight-Gain

Topics: Adult; Aged; Alzheimer Disease; Breast Neoplasms; Cardiovascular Diseases; Cohort Studies; Diet; Double-Blind Method; Embryonal Carcinoma Stem Cells; Estrogens; Estrogens, Non-Steroidal; Female; Follow-Up Studies; Gonadal Steroid Hormones; Hormone Replacement Therapy; Hot Flashes; Humans; Isoflavones; Longevity; Menopause; Menopause, Premature; Middle Aged; Neoplasm Recurrence, Local; Neoplasms, Hormone-Dependent; Neoplasms, Second Primary; Neoplastic Stem Cells; Obesity; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Randomized Controlled Trials as Topic; Safety; Selective Estrogen Receptor Modulators; Survivors; Weight Gain

Pulmonary arterial hypertension is characterized by high pulmonary blood pressure, vascular remodeling and right ventricular hypertrophy. In the present study, we investigated whether genistein would prevent the development of low temperature-induced pulmonary hypertension in broilers. Hemodynamic parameters, vascular remodeling, the expression of endothelial nitric oxide and endothelin-1 content in lung tissue were evaluated. The results demonstrated that genistein significantly reduced pulmonary arterial hypertension and suppressed pulmonary arterial vascular remodeling without affecting broilers' performance. The beneficial effects appeared to be mediated by restoring endothelial function especially endothelial nitric oxide and endothelin-1, two critical vasoactive molecules that associated with the development of hypertension. Genistein supplementation might be a potential therapeutic strategy for the treatment of pulmonary hypertension.

Topics: Animals; Ascites; Chickens; Cold Temperature; Cyclic GMP; Dose-Response Relationship, Drug; Endothelin-1; Endothelium, Vascular; Genistein; Hemodynamics; Hypertension, Pulmonary; Lung; Male; Neovascularization, Pathologic; Nitric Oxide Synthase Type III; Pericardial Effusion; Phytoestrogens; Poultry Diseases; Weight Gain

The progressive decline in estrogen level puts postmenopausal women at a higher risk of developing cardiometabolic diseases. Thus, we evaluated the potential beneficial effects of yacon-based product (YBP) on glycemic profile and intestinal health of postmenopausal rats.. Eighty Wistar rats were randomized into 4 ovariectomized (OVX) groups or 4 celiotomized groups treated with a standard diet (SD) or diet supplemented with YBP at 6% of fructooligosaccharide (FOS)/inulin.. The continued consumption of YBP at 6% of FOS/inulin did not generate liver damage and gastrointestinal disorders. Rats fed with YBP displayed higher food consumption, but this did not increase the body weight gain, abdominal circumference and body fat percentual of OVX rats. Furthermore, we also found that the FOS/inulin fermentation present in the YBP resulted in cecum, ileum and colon crypts hypertrophy and increased the lactic acid levels in the cecal content. We observed an increase of glucagon-like peptide-1 (GLP-1) immunoreactive cells and there was no change in the glucose and insulin plasma levels of YBP-fed OVX rats.. Our findings indicated that YBP when consumed previously and after the menopausal period has important effects on the morphology and function of intestinal mucous of rats and has potential to modulate indirectly the glycemic and insulinemic profiles, weight gain and body fat percentual in the hypoestrogenic period through metabolites produced in the fermentation process.

Topics: Adipose Tissue; Animals; Blood Glucose; Cecum; Dietary Supplements; Female; Glucagon-Like Peptide 1; Hypertrophy; Ileum; Intestinal Mucosa; Intestines; Inulin; Oligosaccharides; Phytoestrogens; Plant Extracts; Postmenopause; Prebiotics; Rats; Rats, Wistar; Weight Gain

Estrogen deficiency during menopause causes a variety of neurological symptoms, including depression. The edible Lion's Mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (HE), is a medicinal mushroom that has the potential for a neuroprotective effect and ameliorating neurological diseases, such as depression, anxiety, and neurodegenerative diseases. HE contains phytoestrogens, including daidzein and genistein. However, the ameliorating effect of HE on menopausal symptoms is not well understood. Here we investigated the impact of methanol extract of the HE fruiting body on depressive-like behavior in postmenopausal model rats. The activation of estrogen receptor alpha (ERα) causes body weight loss and uterine weight gain. Body weight gain and uterine weight loss by estrogen deficiency in ovariectomized (OVX) rats were reversed with 17β-estradiol (E

Topics: Agaricales; Animals; Estradiol; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Genistein; Hericium; Humans; Methanol; Neuroprotective Agents; Ovariectomy; Phytoestrogens; Rats; Weight Gain

Postmenopausal women have a decline in circulating estrogen levels and are more prone to obesity and its related metabolic diseases than premenopausal women are. The absence of safe and effective conventional treatments for postmenopausal obesity has changed the focus to natural products as alternative remedies. Here, ovariectomized rats and LO2 cells were used to study the molecular basis of the effect of dietary phytoestrogens on body weight gain and hepatic steatosis. Dietary phytoestrogens can inhibit ovariectomy (OVX)-induced body weight gain, blood glucose concentration, expression of hepatic lipogenic genes, such as sterol regulatory element binding protein (SREBP)1, acetyl-CoA carboxylase (ACC)1, fatty acid synthase (FAS), and stearoyl-CoA desaturase (SCD)1, and decrease liver triglyceride (TG) content, but later estradiol withdrawal increased expression of SREBP1. Histological analysis of liver showed that dietary phytoestrogens improved OVX-induced morphological abnormalities. OVX and high glucose-induced phosphorylation of signal transducer and activator of transcription (STAT)-3 were inhibited by phytoestrogens treatment. In LO2 cells, inhibition of STAT-3 by siRNA attenuated the increased TG content and expression of SREBP1 induced by high glucose. Phytoestrogens reduced the upregulation of SREBP1 and TG induced by high glucose in LO2 cells. In conclusion, these findings illustrated that dietary phytoestrogens markedly alleviated the derangement of lipid metabolism. The underlying mechanism is probably associated with regulating STAT-3/SREBP1 signaling.

Topics: Animals; Cell Line; Diet; Eating; Female; Glucose; Lipid Metabolism; Lipogenesis; Liver; Ovariectomy; Phytoestrogens; Rats, Sprague-Dawley; STAT3 Transcription Factor; Sterol Regulatory Element Binding Protein 1; Weight Gain

The objective of this study was to confirm the effect of maternal genistein exposure on body weight of male offspring and the metabolic alterations associated with maternal genistein-induced obesity. Pregnant female Sprague-Dawley (SD) rats were supplemented with 300 mg/kg diet of genistein (GEN) or no genistein (CON) throughout pregnancy and lactation. The growth of male offspring was investigated until 12 week age and the mechanism of obesity was studied using metabonomics by ultra performance liquid chromatography and quadrupole time-of-flight (UPLC Q-TOF) MS with electrospray ionization in positive ESI mode (ESI+). Compared with the CON group, body weight, fat pad and food intake of male offspring in GEN group were increased significantly at the age of weeks 10 to 12 (p<0.05). Ten urine principal metabolites contributing to the clusters were identified, including increased 8-Isoprostaglandin F2a, and decreased L-Proline, Betaine, L-Acetylcarnitine, Norsalsolinol, Indoleacrylic acid, L-Tryptophan, Lysophosphatidylcholines (LysoPC) (20 : 4), Lysophosphatidylethanolamines (LysoPE) (18 : 1) and LysoPC (O-18 : 0). Our results confirmed weight-increasing effects of maternal genistein exposure, accompanied by favorable changes in metabolites in the male offspring' urine. Therefore, this research enables us to better understand obesity and predict risk of obesity-related disease by studying metabolites present in the urine.

Topics: Adipose Tissue; Animals; Biomarkers; Chromatography, High Pressure Liquid; Diet; Dietary Supplements; Eating; Female; Genistein; Lactation; Male; Maternal Nutritional Physiological Phenomena; Metabolome; Metabolomics; Obesity; Phytoestrogens; Pregnancy; Prenatal Exposure Delayed Effects; Rats, Sprague-Dawley; Spectrometry, Mass, Electrospray Ionization; Weight Gain

Soy is the main source of phytoestrogens, which has long been used as traditional food. One major subtype of phytoestrogens includes isoflavones and they are scientifically validated for their beneficial actions on many hormone-dependent conditions.. The present study examines the effect of soy isoflavones on letrozole-induced polycystic ovary syndrome (PCOS) rat model.. PCOS was induced in Sprague-Dawley rats with of 1 mg/kg letrozole, p.o. once daily for 21 consecutive days. Soy isoflavones (50 and 100 mg/kg) was administered for 14 days after PCOS induction. Physical parameters (body weight, oestrous cycle determination, ovary and uterus weight) metabolic parameters (oral glucose tolerance test, total cholesterol), steroidal hormone profile (testosterone and 17β-oestradiol), steroidogenic enzymes (3β-hydroxy steroid dehydrogenase (HSD) and 17β-HSD), oxidative stress and histopathology of ovary were studied.. Soy isoflavones (100 mg/kg) treatment significantly altered the letrozole-induced PCOS symptoms as observed by decreased body weight gain (p < 0.05), percentage diestrous phase (p < 0.001), testosterone (p < 0.001), 3β-HSD (p < 0.01) and 17β-HSD (p < 0.001) enzyme activity and oxidative stress. Histological results reveal that soy isoflavones treatment in PCOS rats resulted in well-developed antral follicles and normal granulosa cell layer in rat ovary.. Treatment with soy isoflavones exerts beneficial effects in PCOS rats (with decreased aromatase activity) which might be due to their ability to decrease testosterone concentration in the peripheral blood.. Analysis of physical, biochemical and histological evidences shows that soy isoflavones may be beneficial in PCOS.

Topics: 17-Hydroxysteroid Dehydrogenases; 3-Hydroxysteroid Dehydrogenases; Androgen Antagonists; Animals; Antioxidants; Biomarkers; Blood Glucose; Cholesterol; Disease Models, Animal; Dose-Response Relationship, Drug; Estradiol; Estrous Cycle; Female; Glycine max; Isoflavones; Letrozole; Nitriles; Ovary; Oxidative Stress; Phytoestrogens; Phytotherapy; Plants, Medicinal; Polycystic Ovary Syndrome; Rats, Sprague-Dawley; Testosterone; Time Factors; Triazoles; Uterus; Weight Gain

Endocrine disrupting compounds (EDCs) are hypothesized to promote obesity and early puberty but their interactive effects with hormonally active diets are poorly understood. Here we assessed individual and combinatorial effects of soy diet or the isoflavone genistein (GEN; administered as the aglycone genistin GIN) with bisphenol A (BPA) on body weight, ingestive behavior and female puberal onset in Wistar rats. Soy-fed dams gained less weight during pregnancy and, although they consumed more than dams on a soy-free diet during lactation, did not become heavier. Their offspring (both sexes), however, became significantly heavier (more pronounced in males) pre-weaning. Soy also enhanced food intake and accelerated female pubertal onset in the offspring. Notably, pubertal onset was also advanced in females placed on soy diet at weaning. Males exposed to BPA plus soy diet, but not BPA alone, had lighter testes. BPA had no independent effects.

Topics: Age Factors; Animal Nutritional Physiological Phenomena; Animals; Benzhydryl Compounds; Dietary Proteins; Eating; Endocrine Disruptors; Female; Genistein; Male; Maternal Nutritional Physiological Phenomena; Nutritional Status; Obesity; Phenols; Phytoestrogens; Pregnancy; Prenatal Exposure Delayed Effects; Rats, Wistar; Risk Assessment; Sexual Maturation; Soybean Proteins; Weight Gain

To determine whether daidzein improves insulin resistance by modifying weight gain, visceral fat accumulation, blood lipids and serum cytokines levels in ovariectomized Sprague-Dawley rats.. Twenty-eight 12-week-old female rats were divided into three groups: the sham-operated group (SHAM) (n =10), the ovariectomized group receiving daidzein therapy (DAID) (n =10), and the ovariectomized control group (Control) (n =8). The rats in the DAID group received 50 mg/kg daidzein via gavage daily. Weight and food intake were recorded every 2 weeks. All of the animals were euthanized 12 weeks after ovariectomy, after which their fasting insulin, glucose, blood lipids, estradiol, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), adiponectin and leptin levels were measured.. After 12 weeks, the ovariectomized rats demonstrated an increase in their body weight and visceral fat; compared to the SHAM rats, the ovariectomized rats also experienced a significant increase in their serum IL-6 levels and insulin resistance, which was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR) (p <0.05). Daidzein therapy decreased weight gain, visceral fat, the HOMA-IR index and IL-6 levels that were induced by ovariectomy. Rats which had received daidzein therapy had lower levels of TNF-α, leptin and blood lipids (except for high density lipoprotein cholesterol) than the other two groups. IL-6 levels positively correlated with the HOMA-IR index in all of the rats after adjustment for body weight (r =0.495; p =0.016).. We conclude that daidzein can improve insulin resistance induced by ovariectomy by decreasing weight gain, visceral fat accumulation, blood lipids, TNF-α, leptin and IL-6 levels.

Topics: Analysis of Variance; Animals; Blood Glucose; Cholesterol, HDL; Cholesterol, LDL; Female; Insulin Resistance; Interleukin-6; Intra-Abdominal Fat; Isoflavones; Leptin; Ovariectomy; Phytoestrogens; Rats; Rats, Sprague-Dawley; Triglycerides; Tumor Necrosis Factor-alpha; Weight Gain

The present study was conducted to clarify the effects of coumestrol administration to maternal mice during pregnancy and lactation on serum Ca and Ca metabolism in their neonatal mice. From 6.5 to 16.5 days post coitus and from 3 to 10 days after parturition, maternal mice were administered at 200 µg/kg body weight/day of coumestrol. Coumestrol administration did not affect weight gains, serum Ca and the expression of vitamin D receptor (VDR) protein in the kidney of neonatal mice, but weight gains of maternal mice were decreased by coumestrol administration. Coumestrol administration increased the messenger RNA (mRNA) expressions of epithelial Ca channels 1 (ECaC1) and VDR in the kidney of neonatal mice, and also increased the mRNA expressions of ECaC2 in the kidney and small intestine of male neonatal mice. The mRNA expressions of ECaC1, ECaC2, calbindin-D(9k) (CaBP-9k) and estrogen receptor (ER)α in the kidney and VDR in the small intestine of male neonatal mice were higher than those of female mice. Thus, coumestrol administration to maternal mice during pregnancy and lactation may affect renal Ca metabolism in neonatal mice, especially male neonatal mice via maternal milk.

Topics: Animals; Animals, Newborn; Calbindins; Calcium; Calcium Channels; Coumestrol; Estrogen Receptor alpha; Female; Intestine, Small; Kidney; Lactation; Male; Maternal-Fetal Exchange; Mice; Mice, Inbred ICR; Phytoestrogens; Pregnancy; Pregnancy, Animal; Receptors, Calcitriol; RNA, Messenger; S100 Calcium Binding Protein G; TRPV Cation Channels; Weight Gain

In mice, exposure to isoflavones (ISO), abundant in soy infant formula, during the first 5 d of life alters structural and functional development of reproductive organs. Effects of longer exposures are unknown. The study objective was to evaluate whether exposure to a combination of daidzein and genistein in the first 10 compared to 5 d of life results in greater adverse effects on ovarian and uterine structure in adult mice. Thirteen litters of 8-12 pups were cross-fostered and randomized to corn oil or ISO (2 mg daidzein + 5 mg genistein/kg body weight/d) for the first 5 or 10 d of life. The 10-d protocol mimicked the period when infants are fed soy protein formula (SPF) but avoids the time when suckling pups can consume mother's diet. Body and organ weights, and histology of ovaries and uteri were analyzed. There were no differences in the ovary or uterus weight, number of ovarian follicles, number of multiple oocyte follicles, or percent of ovarian cysts with 5 or 10 d ISO intervention compared to respective controls. The 10-d ISO group had higher body weights from 6 d to 4 mo of age and a higher percent of hyperplasia in the oviduct than the respective control. Lower number of ovarian corpus lutea and a higher incidence of abnormal changes were reported in the uteri of both ISO groups compared to their respective controls. Five and 10-d exposure to ISO had similar long-lasting adverse effects on the structure of ovaries and uterus in adult mice. Only the 10-d ISO exposure resulted in greater body weight gain at adulthood.

Topics: Animals; Animals, Suckling; Female; Genistein; Humans; Hyperplasia; Infant; Infant Formula; Isoflavones; Lactation; Maternal Nutritional Physiological Phenomena; Mice; Mice, Inbred Strains; Ovary; Oviducts; Phytoestrogens; Random Allocation; Soy Foods; Uterus; Weight Gain

Postmenopausal women are at higher risk for obesity and insulin resistance due to the decline of estrogen, but genistein, a phytoestrogen, may reduce the risks of these diet-related diseases. In this study, we hypothesized that supplemental genistein has beneficial effects on insulin resistance in an ovariectomized rat model by modulating lipid metabolism. Three weeks after a sham surgery (sham) or an ovariectomy (OVX), ovariectomized Sprague-Dawley rats were placed on a diet containing 0 (OVX group) or 0.1% genistein for 4 weeks. The sham rats were fed a high-fat diet containing 0% genistein and served as the control group (sham group). The ovariectomized rats showed increases in body weight and insulin resistance index, but genistein reduced insulin resistance index and the activity of hepatic fatty acid synthetase. Genistein was also associated with increased activity of succinate dehydrogenase and carnitine palmitoyltransferase and the rate of β-oxidation in the fat tissue of rats. The ovariectomized rats given genistein had smaller-sized adipocytes. Using gene-set enrichment analysis (GSEA) of microarray data, we found that a number of gene sets of fatty acid metabolism, insulin resistance, and oxidative stress were differentially expressed by OVX and reversed by genistein. This systemic approach of GSEA enables the identification of such consensus between the gene expression changes and phenotypic changes caused by OVX and genistein supplementation. Genistein treatment could help reduce insulin resistance through the amelioration of OVX-induced metabolic dysfunction, and the GSEA approach may be useful in proposing putative targets related to insulin resistance.

Topics: Adipose Tissue; Animals; Carnitine O-Palmitoyltransferase; Diet, High-Fat; Dietary Supplements; Disease Models, Animal; Fatty Acid Synthases; Female; Gene Expression; Genistein; Glycine max; Insulin Resistance; Lipid Metabolism; Liver; Microarray Analysis; Obesity; Ovariectomy; Oxidation-Reduction; Oxidative Stress; Phytoestrogens; Phytotherapy; Plant Extracts; Postmenopause; Rats; Rats, Sprague-Dawley; Succinate Dehydrogenase; Weight Gain

Recently, growing multiple uses of silymarin (SIL) as a complementary and alternative medicine, for alcohol-induced liver disease, acute and chronic viral hepatitis, as well as some other nonhepatic indications have been reported. Therefore, more attention should be paid for the hormonal side effects of SIL. Since the available data on the possible estrogenic effects of SIL is rather rare, this study aimed to further elucidate the different estrogenic effects and antiosteoporotic activity of SIL in ovariectomized (OVX) rats. OVX rats were treated chronically (12 weeks) with ethinylestradiol (EE) or SIL. Uterine and body weight were measured in all animals. Biochemical markers of bone formation (total alkaline phosphatase (ALP), calcium, phosphorus and osteocalcin), endocrinological analysis (estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH) and parathyroid hormone (PTH)) and serum total cholesterol and total lipids were estimated. Formalin fixed femora and uteri specimens were used for histopathological examination. In addition, the binding property of SIL to the two estrogen receptors (ER) subtypes was tested by molecular docking. EE (strong) and SIL (mild) stimulated uterine weight (increased uterus hyperplastic endometrial glands) but EE only prevented body weight gain following OVX. Treatment of OVX rats with both EE and SIL resulted in protection of trabecula thickness, decreased serum levels of ALP and increased serum levels of both calcium and phosphorus. In contrast to EE, SIL did not decrease OVX induced serum osteocalcin. EE not SIL decreased serum cholesterol, total lipids, LH and FSH and increased serum E2. Both EE and SIL increased serum PTH. The docking study revealed a high affinity of SIL towards ERbeta. In conclusion, findings derived in the present study presented an overview of SIL many estrogenic effects in OVX rats. SIL significantly prevents the bone loss in rats induced by OVX with mild proliferative effects in uterus. The observed effects may be due to additive beneficial effect of SIL on bone either due to direct interaction with ERbeta or increasing bone formation parameters including calcium, phosphorus, osteocalcin and PTH.

Topics: Alkaline Phosphatase; Animals; Biomarkers; Bone and Bones; Bone Density Conservation Agents; Calcium; Endometrial Hyperplasia; Estradiol; Estrogen Receptor beta; Ethinyl Estradiol; Female; Hormones; Lipids; Organ Size; Osteocalcin; Osteoporosis; Ovariectomy; Phosphorus; Phytoestrogens; Phytotherapy; Plant Extracts; Rats; Selective Estrogen Receptor Modulators; Silybum marianum; Silymarin; Uterus; Weight Gain

High soy diets reduce injury in rat models of focal cerebral ischemia and are proposed as alternatives to hormone replacement therapy for postmenopausal women. The present study tests the hypothesis that the major soy isoflavone genistein and the daidzein metabolite equol are neuroprotective in transient focal cerebral ischemia in male and ovariectomized (OVX) female rats by inhibiting oxidative stress. Genistein is the primary circulating soy isoflavone in humans, whereas equol is the primary circulating isoflavone in rats. Male and OVX female Sprague-Dawley rats were fed an isoflavone-reduced diet alone or supplemented with genistein (500 ppm) or equol (250 ppm) for 2 wk prior to 90-min transient middle cerebral artery occlusion followed by reperfusion under isoflurane anesthesia. Indices of oxidative stress were determined 24 h after reperfusion, and cerebral injury was evaluated 3 days after reperfusion. Genistein and equol significantly reduced infarct size in both sexes. Further studies in OVX female rats revealed that this neuroprotection was accompanied by a decrease in NAD(P)H oxidase activity and superoxide levels in the brain. In addition, equol reduced plasma thiobarbituric acid reactive substances, and neurological deficits up to 7 days after injury. There were no significant differences in cerebral blood flow among treatment groups. In conclusion, dietary soy isoflavones are neuroprotective in transient focal cerebral ischemia in male and OVX female rats. These isoflavones may protect the brain via increases in endogenous antioxidant mechanisms and reduced oxidative stress.

Topics: Animals; Brain Ischemia; Diet; Equol; Female; Genistein; Isoflavones; Male; Ovariectomy; Oxidative Stress; Phytoestrogens; Rats; Sex Characteristics; Thiobarbituric Acid Reactive Substances; Weight Gain

Non-alcoholic fatty liver disease (NAFLD) has been deeply associated with visceral adiposity, adipose tissue inflammation and a variety of adipocytokines. We reported previously that genistein inhibited NAFLD by enhancing fatty acid catabolism. However, this molecular approach focused on hepatic metabolism. Thus, we have attempted to determine whether this anti-steatotic effect of genistein is linked to visceral adipocyte metabolism. C57BL/6J mice were fed on normal-fat (NF) diet, high-fat (HF) diet and HF diet supplemented with genistein (1, 2 and 4 g/kg diet) for 12 weeks. Mice fed on the HF diet gained body weight, exhibited increased visceral fat mass and elevated levels of serum and liver lipids, and developed NAFLD, unlike what was observed in mice fed on the NF diet. However, genistein supplementation (2 and 4 g/kg diet) normalised these alternations. In the linear regression analysis, visceral fat (R 0·77) and TNFα (R 0·62) were strongly correlated with NAFLD among other NAFLD-related parameters. Genistein supplementation suppressed the hypertrophy of adipocytes via the up-regulation of genes involved in fatty acid β-oxidation, including PPARα, 5'-AMP-activated protein kinase and very long-chain acyl CoA dehydrogenase, as well as through the down-regulation of genes associated with adipogenesis or lipogenesis, including liver X receptor-α, sterol-regulatory element-binding protein-1c, PPARγ, retinoid X receptor-α and acetyl CoA carboxylase 2. Moreover, genistein supplementation augmented an anti-steatohepatitic adiponectin TNF and reduced a steatohepatitic TNFα. Collectively, these findings show that genistein may prevent NAFLD via the regulation of visceral adipocyte metabolism and adipocytokines.

Topics: Adipocytes; Adipogenesis; Animals; Dietary Fats; Fatty Liver; Gene Expression Regulation; Genistein; Glycine max; Hypertrophy; Hypolipidemic Agents; Intra-Abdominal Fat; Linear Models; Lipid Metabolism; Lipogenesis; Male; Mice; Mice, Inbred C57BL; Phytoestrogens; Plant Extracts; Tumor Necrosis Factors; Weight Gain

Soy isoflavone preparations, such as purified genistein and a soy extract (Novasoy), were reported previously to exert beneficial effects on bones. Our purpose in this study was to compare the effects of genistein and Novasoy on 3-dimensional trabecular bone parameters and the expression of bone-specific genes in ovariectomized (OVX) mice. The sham-operated mice were fed the control diet and OVX mice were fed diets containing genistein or Novasoy or the control diet, with or without 17beta-estradiol treatment, for 5 wk. Trabecular bone parameters of tibias were measured by microcomputed tomography and gene expression was assayed by real-time PCR. Consumption of diets containing genistein or Novasoy partially prevented the ovariectomy-induced increase in body weight but did not alter the uterus weight of the OVX mice. Novasoy, but not purified genistein, significantly preserved trabecular bone mass, bone volume, and trabecular bone separation in the proximal tibial metaphysis. Purified genistein decreased mRNA expression of receptor activator of nuclear factor-kappaB ligand (RANKL), carbonic anhydrase II, and cathepsin K and enhanced the ratio of osteoprotegrin:RANKL mRNA expression in the tibial head of the OVX mice. In contrast, the diet containing Novasoy suppressed the OVX-induced increase in serum alkaline phosphatase but did not alter bone-specific gene expression of tibia. Our study demonstrated that a soy extract containing a similar level of genistein in the form of Novasoy is more effective than purified genistein in improving tibial trabecular bone quality in OVX mice, but the mechanism of action might be distinct from that of genistein.

Topics: Animals; Bone and Bones; Carbonic Anhydrase II; Cathepsin K; Female; Gene Expression Regulation; Genistein; Mice; Mice, Inbred C57BL; Osteoporosis; Ovariectomy; Phytoestrogens; Plant Extracts; RANK Ligand; RNA, Messenger; Soy Foods; Specific Pathogen-Free Organisms; Weight Gain

The ovariectomized (OVX) rat, as an established animal model of human osteoporosis, was adopted in the present experiment to study the protective effects of sodium daidzein sulfonate (SDS) on trabecular bone. Six-month-old Sprague-Dawley rats were sham-operated or ovariectomized. Five days later, the OVX rats were randomly assigned to one of three experimental groups and treated for 90 days with vehicle, 17beta-estradiol (E(2)) or SDS. Compared with OVX rats, SDS administration (15 mg/kg) prevented OVX-induced decrease in lumbar vertebral and femoral bone mineral density (BMD), and significantly increased bone mechanical strength parameters, including ultimate stress and elastic modulus. In the OVX group, the structure of trabecular plate in the femoral head was absorbed and became progressively thinner or was removed completely, accompanied by enlargement of marrow cavities and amalgamation of two or more marrow cavities. Administration of SDS and E(2 )prevented the change of trabecular bone microarchitecture induced by OVX, increasing the trabecular bone area and trabecular thickness, while decreasing the trabecular separation. These results indicate that SDS administration prevents OVX-induced decrease in BMD and bone mechanical strength, and has a moderate protective effect on the microarchitecture of trabecular bone in aged Sprague-Dawley rats.

Topics: Amino Acids; Animals; Bone and Bones; Bone Density; Bone Resorption; Dose-Response Relationship, Drug; Estradiol; Female; Femur Head; Isoflavones; Lumbar Vertebrae; Microscopy, Electron, Scanning; Organ Size; Osteocalcin; Ovariectomy; Phytoestrogens; Random Allocation; Rats; Rats, Sprague-Dawley; Tensile Strength; Uterus; Weight Gain

In veal calf production plant-based proteins are frequently included in milk replacer fed to the animals. Since soy products, which are mostly used, are known for their high levels of phyto-oestrogens, the effects of these feeds on the veal calf prostate were examined. Goal was to determine whether these compounds could interfere with histological screening for oestrogenic growth promoters. In a feeding experiment, four groups of veal calves fed plant-based protein-supplemented milk replacer (PBM), containing 5% soy concentrate, 5% soy isolate, 5% wheat gluten and 2% potato protein, for 4 weeks were compared to animals fed dairy-based control feed (DBM); animals treated with estradiol benzoate, diethylstilbestrol and ethinylestradiol served as positive controls. Daidzein and genistein levels measured in feed and urine showed high levels of genistein and daidzein in the soy isolate and soy concentrate supplemented feeds. Genistein and daidzein were also found in the urine of the animals that were fed these feeds. Haematoxylin-eosin-stained prostate sections of PBM-fed animals showed slight hyperplasia and some dilated tubules as compared to the DBM-fed group, but no metaplasia, which is used for screening for oestrogenic hormones. The positive controls showed extensive squamous metaplasia. Immunohistochemical staining for cytokeratin 5 (using RCK 103 monoclonal antibody) in basal cells showed a normal staining pattern of basal cells in the DBM-fed calves and extensive basal cell proliferation and squamous metaplasia in the oestrogen-treated positive control animals. PBM-fed calves showed no increase of basal cell staining but showed elongations of the basal cells in most animals, sometimes resulting in circular figures. It is concluded that the feeds examined in this study did not interfere with histological screening for oestrogens in male veal calves.

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Animals, Newborn; Cattle; Estrogens, Non-Steroidal; Genistein; Glycine max; Immunohistochemistry; Isoflavones; Male; Phytoestrogens; Prostate; Random Allocation; Weight Gain

There is a great deal of controversy surrounding the issue of hormone replacement therapy after transplantation. The question whether or not this therapy has effects in cardiac allograft vasculopathy (CAV), the Achilles heel of cardiac transplantation or other unique aspects of allograft function is still unknown.. We investigated the long-term effect of 17beta-estradiol as well as phytoestrogen Coumestrol, a synthetically produced phytoestrogen, on the development of CAV and the degree of fibrosis in an ovariectomized female heterotopic chronic allograft model (LEW-F344).. We found that, 150 days after transplantation, no significant effect of estrogen application on intimal thickening of coronary arteries was observed. 17beta-estradiol and phytoestrogen Coumestrol did significantly reduce the perivascular immune reaction. However, the immune effect had no consequence on the intensity of CAV. Although neither 17beta-estradiol nor phytoestrogen Coumestrol revealed a positive effect on CAV, the group of animals treated with 17beta-estradiol showed the highest decline in heart function and the most distinct fibrosis.. 17beta-estradiol does not affect CAV positively, but worsens cardiac allograft function and leads to increased fibrosis. This is the first study showing a negative effect of 17-beta-estradiol after heart transplantation in the long term.

Topics: Animals; Body Weight; Coumestrol; Disease Models, Animal; Estradiol; Female; Heart Transplantation; Phytoestrogens; Postoperative Complications; Rats; Rats, Inbred F344; Rats, Inbred Lew; T-Lymphocytes; Transplantation, Homologous; Transplantation, Isogeneic; Uterus; Weight Gain

Isoflavones are soy compounds that possess weak estrogenic and antiestrogenic activities. In addition, phytochemicals, including isoflavones, may play a role in regulating seasonal reproductive cycles. As soy is a common constituent in poultry diets, the effect of these compounds on the reproductive system of production birds may be of concern. The present study examined the putative effects of soy isoflavones supplemented into the diet at 1 and 5% using endpoints of growth and reproduction in the Japanese quail. Isoflavones did not exert an effect on growth, feed intake, growth:feed, or the weight of the estrogen-sensitive immature oviduct in female quail. Furthermore, isoflavones did not influence the growth of the oviduct stimulated by exogenous estradiol. Similarly, isoflavones did not influence growth, feed intake, or growth:feed in male quail. However, isoflavones at 1%, but not 5%, in the diet reduced photoperiod-induced testis development 40% vs. control. In contrast, isoflavones did not influence testis regression stimulated by exogenous estradiol in sexually maturing male quail. The present results suggest that isoflavones may exert modest endocrine disruptor-like effects on reproduction in male, but not female, quail.

Topics: Animal Feed; Animals; Coturnix; Dose-Response Relationship, Drug; Female; Isoflavones; Male; Oviducts; Photoperiod; Phytoestrogens; Reproduction; Sex Factors; Sexual Maturation; Testis; Weight Gain

Genistein, a soybean-originated isoflavone, is widely consumed by humans for putative beneficial health effects but its estrogenic activity may adversely affect the development of male reproductive system. Twenty one-day-old ICR mice weaned from dams fed with a soybean-based diet throughout gestation and lactation were exposed by gavage to genistein (2.5 mg/kg b.w./day) or 17beta-estradiol (7.5 microg/kg b.w./day) for five weeks. Corn oil was used as a negative control. The animals were fed with a casein-based AIN-76A diet throughout the experimental periods. There were no significant differences in body and organ weights of mice among experimental groups. No significant differences in sperm counts and sperm motile characteristics were found between control and genistein groups. Treatment of 17beta-estradiol caused a significant decrease in prostate weight and epididymal sperm counts compared to the control (p<0.05). The levels of phospholipid hydroxide glutathione peroxidase in the testis and prostate of mice exposed to genistein or 17beta-estradiol were significantly higher than that of the control mice (p<0.05). 17beta-estradiol treatment caused degeneration and apoptosis of germ cells in the testis, depletion and degeneration in the epididymal epithelium, and hyperplasia of mucosal fold region in the prostate of mice. Genistein treatment did not cause any lesion in the testis, epididymis, and prostate. These results suggest that dietary uptake of genistein during juvenile period may not affect male reproductive development and functions.

Topics: Animal Feed; Animals; Epididymis; Estradiol; Female; Genistein; Glutathione Peroxidase; Glycine max; Male; Mice; Mice, Inbred ICR; Organ Size; Phospholipid Hydroperoxide Glutathione Peroxidase; Phytoestrogens; Prostate; Sexual Maturation; Sperm Count; Testis; Weight Gain

A study was conducted to determine the effects of dietary factors in natural ingredient and purified diets on uterine weights of immature CD-1 mice used in uterotrophic bioassays. Factors evaluated included body weight gain, dietary phytoestrogen content, total metabolizable energy, and percent crude fiber. Fifteen to 147 mice per group, housed 5 per cage, were randomly assigned to each of the 20 test diets. The test diets were fed for 7 days to 15-day old immature female CD-1 mice and their body weight gain and uterine weights were determined. Analysis of covariance procedures were used to evaluate differences in uterine weights, after adjusting for body weight and time-related trends. Fisher's least significant difference test was used to compare adjusted uterine weights and weight gains among the test diets. Additionally, multiple linear regression procedures were used to identify those characteristics of the rodent diet that were most predictive of the adjusted uterine weights. Total metabolizable energy was significantly (P < 0.01) correlated with and was predictive of uterine weights. The following dietary variables were not significantly predictive of uterine weights: total daidzein and genistein content, percent protein, fat, N-FE (carbohydrates) or percent crude fiber. We concluded that: (1) total metabolizable energy (ME) in natural ingredient or purified diets has a significant (P < 0.01) effect on the uterine weights of immature mice used in 7-day uterotrophic bioassays; (2) a standardized, estrogen-free diet with a constant level of ME should be used for conducting uterotrophic assays when comparing results between different laboratories or when determining the estrogenic or anti-estrogenic activity of endocrine disruptor compounds; (3) the mouse uterotrophic assay remains a sensitive bioassay for assessing chemicals for estrogenic activity or for the detection of total estrogenic activity in rodent diets that may be contaminated with estrogenic compounds, and (4) chemical assays should be used to detect or measure low levels of the phytoestrogens in rodent diets.

Topics: Animal Feed; Animals; Biological Assay; Diet; Dietary Fiber; Energy Metabolism; Estrogens, Non-Steroidal; Female; Isoflavones; Mice; Phytoestrogens; Plant Preparations; Random Allocation; Receptors, Estrogen; Uterus; Weight Gain