stilbenes and Infertility--Female

Topics: Adult; Amenorrhea; Clomiphene; Female; Humans; Infertility, Female; Ovulation; Stilbenes

Topics: Amenorrhea; Clinical Trials as Topic; Clomiphene; Female; Humans; Infertility, Female; Ovulation; Pregnancy; Stilbenes

Does resveratrol counteract age-associated infertility in a mouse model of reproductive aging?. Long-term-oral administration of resveratrol protects against the reduction of fertility with reproductive aging in mice.. Loss of oocytes and follicles and reduced oocyte quality contribute to age-associated ovarian aging and infertility. Accumulation of free radicals with age leads to DNA mutations, protein damage, telomere shortening, apoptosis and accelerated ovarian aging. Increasing evidence shows that resveratrol, enriched in certain foods, for example red grapes and wine, has anti-tumor and anti-aging effects on somatic tissues by influencing various signaling pathways, including anti-oxidation, as well as activating Sirt1 and telomerase. We investigated the potential of resveratrol to stave off ovarian aging in the inbred C57/BL6 mouse model.. Young C57/BL6 females (aged 2-3 months) were fed with resveratrol added to drinking water at 30 mg/l (providing ∼7.0 mg/kg/day) for 6 or 12 months, and the fertility and ovarian functions were compared among mice treated with or without resveratrol, and young mice served as reproductive controls. Experiments were repeated three times, with an average of 25 females randomly allocated to each treatment group for each repeat.. Reproductive performance of female mice was determined by litter size, ovarian follicles and oocyte quantity and quality, and compared with age-matched controls. The impact of resveratrol on telomeres and telomerase activity, and expression of genes associated with cell senescence also was evaluated.. Young mice fed with resveratrol for 12 months retained the capacity to reproduce, while age-matched controls produced no pups. Consistently, mice fed with resveratrol for 12 months exhibited a larger follicle pool than controls (P < 0.05). Furthermore, telomerase activity, telomere length and age-related gene expression in ovaries of mice fed with resveratrol resembled those of young mice, but differed (P < 0.05) from those of age-matched old mice. Resveratrol improved (P < 0.05) the number and quality of oocytes, as evidenced by spindle morphology and chromosome alignment. Also, resveratrol affected embryo development in vitro in a dose-dependent manner.. The doses of resveratrol and the experimental conditions used by different research groups have varied considerably, and the dosage influences both the effectiveness and toxicity of resveratrol. Fine-tuning the dosage of resveratrol likely will optimize its anti-aging effects on ovarian function.. Our data provide a proof of principle of the fertility-sparing effect of resveratrol in female mice. Although depletion of the ovarian reserve of high-quality oocytes also contributes to increased infertility with reproductive aging in women, the data obtained using a mouse model may not extrapolate directly to human reproduction, and more extensive research is needed if any clinic trials are to be attempted.. This work was supported by MOST of China National Basic Research Program (grant number: 2010CB94500 and 2012CB911200). The authors have no competing interests to declare.

Topics: Aging; Animals; Antioxidants; Apoptosis; Disease Models, Animal; Ectogenesis; Female; Gene Expression Regulation, Developmental; Infertility, Female; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Oogenesis; Ovary; Oxidative Stress; Primary Ovarian Insufficiency; Proto-Oncogene Proteins p21(ras); Random Allocation; Resveratrol; Sirtuin 1; Stilbenes; Telomerase; Telomere Shortening

We present a hypothesis emphasizing the role of mitochondrial dysfunction in reproductive senescence and suggesting the use of mitochondrial nutrients as an adjuvant treatment in older patients with infertility.

Topics: Age Factors; Aging; Animals; Dietary Supplements; DNA, Mitochondrial; Energy Metabolism; Female; Humans; Infertility, Female; Mice; Mice, Inbred ICR; Mitochondria; Oocytes; Pregnancy; Resveratrol; Stilbenes; Thioctic Acid; Ubiquinone

Niemann-Pick type C1 (NPC) disease is an autosomal recessive neurodegenerative disorder. One feature of the mouse model of NPC1 is it's infertility. We have made transgenic mice which express the Npc1 protein exclusively in fibrillary astrocytes, using the glial fibrillary acidic protein (GFAP) promoter. This selective expression of Npc1 corrects sterility in GFAP-Npc1(-/-), Npc1(-/-) mice. Counts of acidophils in the pituitary of GFAP-Npc1E, Npc1(-/-) mice, as compared Npc1(-/-) mice, and measurements of dopamine D2 receptor (DRD2) mRNA in the pituitary, suggest mechanisms for fertility enhancement. We conclude that the correction of sterility in GFAP-Npc1E, Npc1(-/-) mice is a result of restoring hypothalamic control of the pituitary.

Topics: Animals; Base Sequence; Biphenyl Compounds; Disease Models, Animal; DNA Primers; Female; Hypothalamo-Hypophyseal System; Infertility, Female; Intracellular Signaling Peptides and Proteins; Mice; Mice, Inbred BALB C; Mice, Knockout; Neuroglia; Niemann-Pick C1 Protein; Niemann-Pick Diseases; Ovary; Proteins; Receptors, Dopamine D2; RNA, Messenger; Stilbenes

Topics: Animals; Clomiphene; Dimethylamines; Estradiol; Estrogen Antagonists; Estrus; Female; Humans; Infertility, Female; Menstruation; Ovary; Phenyl Ethers; Pregnancy; Progesterone; Steroids; Stilbenes

Topics: Body Temperature; Cervix Mucus; Chorionic Gonadotropin; Diethylstilbestrol; Dimethylamines; Estrogen Antagonists; Estrogens; Female; Humans; Hysterosalpingography; Infertility, Female; Ovulation; Phenyl Ethers; Pregnancy; Stilbenes; Time Factors

Topics: Clomiphene; Female; Humans; Infertility, Female; Male; Ovulation; Polycystic Ovary Syndrome; Stilbenes

Topics: Adult; Clomiphene; Female; Humans; Hydatidiform Mole; Infertility, Female; Ovulation; Pregnancy; Stilbenes

Topics: Clomiphene; Female; Humans; In Vitro Techniques; Infertility, Female; Ovulation; Stilbenes

Topics: Adrenal Hyperplasia, Congenital; Adult; Chorionic Gonadotropin; Clomiphene; Estrogens, Conjugated (USP); Female; Humans; Infertility, Female; Ovulation; Polycystic Ovary Syndrome; Pregnancy; Stilbenes

Topics: Clomiphene; Female; Humans; Infertility, Female; Stilbenes

Topics: Amenorrhea; Chorionic Gonadotropin; Female; Follicle Stimulating Hormone; Humans; Infertility, Female; Menorrhagia; Stilbenes

Topics: Adult; Amenorrhea; Body Temperature; Clomiphene; Female; Humans; Infertility, Female; Ovulation; Stilbenes

Topics: Clomiphene; Female; Humans; Hypothalamus; Infertility, Female; Ovulation; Polycystic Ovary Syndrome; Stilbenes; Stress, Physiological

Topics: Adult; Clomiphene; Female; Humans; Infertility, Female; Pregnancy; Stilbenes

Topics: Adult; Clomiphene; Female; Humans; Infertility, Female; Ovulation; Pregnancy; Stilbenes

Topics: Amenorrhea; Clomiphene; Cortisone; Drug Therapy; Female; Humans; Infertility; Infertility, Female; Ovary; Ovulation; Polycystic Ovary Syndrome; Stilbenes; Surgical Procedures, Operative

Topics: 17-Ketosteroids; Adrenogenital Syndrome; Amenorrhea; Chiari-Frommel Syndrome; Clomiphene; Drug Therapy; Estrogens; Female; Gonadotropins; Humans; Infertility; Infertility, Female; Ovulation; Pharmacology; Polycystic Ovary Syndrome; Pregnanediol; Stilbenes; Toxicology; Urine

Topics: 17-Ketosteroids; Adenocarcinoma; Atrophy; Chorionic Gonadotropin; Clomiphene; Diagnosis; Drug Therapy; Endometriosis; Endometrium; Female; Follicle Stimulating Hormone; Genital Diseases, Female; Gonadotropins; Humans; Hyperplasia; Infertility; Infertility, Female; Ovulation; Pathology; Polycystic Ovary Syndrome; Stilbenes; Toxicology; Urine; Uterine Neoplasms

Topics: Clomiphene; Female; Humans; Infertility; Infertility, Female; Stilbenes

Topics: Amenorrhea; Clomiphene; Endometritis; Female; Infertility, Female; Ovulation; Stilbenes

Topics: Amenorrhea; Clomiphene; Female; Humans; Infertility, Female; Ovulation; Stilbenes

Topics: Adult; Amenorrhea; Clomiphene; Female; Gonadotropins, Pituitary; Humans; Infertility, Female; Ovulation; Pregnancy; Statistics as Topic; Stilbenes; Urine

Topics: Amenorrhea; Clomiphene; Dysmenorrhea; Female; Humans; Infertility; Infertility, Female; Ovarian Diseases; Stilbenes

Topics: Amenorrhea; Clomiphene; Drug Therapy; Endometrial Hyperplasia; Female; Fertilization; Humans; Infertility; Infertility, Female; Menstruation Disturbances; Stilbenes; Toxicology

Topics: Clomiphene; Female; Humans; Infertility; Infertility, Female; Laparoscopy; Ovary; Ovulation; Ovulation Induction; Pharmacology; Photography; Stilbenes

Topics: Adrenal Cortex Hormones; Autoimmune Diseases; Blood Group Incompatibility; Chlormadinone Acetate; Congenital Abnormalities; Dydrogesterone; Female; Genitalia; Genitalia, Female; Humans; Hydroxyprogesterones; Infertility, Female; Menstruation Disturbances; Norethindrone; Norethynodrel; Pelvic Inflammatory Disease; Progestins; Psychosomatic Medicine; Stilbenes

Topics: Amenorrhea; Female; Humans; Infertility; Infertility, Female; Ovarian Cysts; Ovarian Neoplasms; Ovulation; Polycystic Ovary Syndrome; Stilbenes