Reproductive lifespan in female mammals is related to the size of primordial follicles pool, which relies on the balance between activated and quiescent primordial follicles. Therefore, the molecular mechanisms of recruiting and maintaining quiescence of primordial follicles have become hot research topics recently. Multiple studies have shown that genetic mutations, local ovarian autocrine and paracrine factors, proto-oncogene and tumor-suppressor genes are involved in the maintenance of balance between quiescent and activated primordial follicles. In the present review, we summarize recent research progress of the important signaling molecules and pathways that maintain the quiescence of primordial follicles.
Animals ; Female ; Humans ; Ovarian Follicle ; physiology ; Signal Transduction

The present experiments were conducted to evaluate the effects of follicular fluid on maturation of bovine follicular oocytes. TC medium 199 seemed to be in adequate for this purpose since a high proportion (ranging 84.1. to 97.0%) of the oocytes were able to resume meiotic division in both media-with or without the addition of follicular fluid. This implies a possible similarity between TC medium 199 and follicular fluid with regard to the components initiating meiosis. Actually, TC medium 199 contains amino acids, vitamins and carbohydrates most of which are also found in follicular fluid. For this reason, the effect of follicular fluid on the ovum maturation was investigated by applying Krebs-Ringer bicarbonate solution (SECM), which was main1y composed of the salts, pyruvate and lactate. When the oocytes were cultured in SECM without the addition of follicular fluid, only 7-14% of them resumed meiotic division within 30 hours. However, when follicular fluid was added, the proportion of oocytes undergoing maturation was sharply increased to about 70%. Among the groups cultured in media containing different concentrations of follicular fluid, the proportion of the oocytes in meiosis remained constant, In pure follicular fluid, 87-89% of the oocytes showed enhancement of meiotic division. The presence of the follicular fluid contributed to a decrease in the production of degenerative oocytes. As a consequence it has been noted that addition of follicular fluid to the culture medium provides a more beneficial environment for cow oocytes. Meiotic division is initiated and production of degenerative oocytes is inhibited.
Animal ; Cattle ; Cells, Cultured ; Culture Media ; Female ; Meiosis ; Oocytes/physiology* ; Ovarian Follicle/physiology* ; Ovum/physiology*

Anti-Müllerian hormone (AMH) is a member of the transforming growth factor (TGF)-beta superfamily and mainly expressed by the granulosa cells of ovarian follicles. In women AMH is only expressed in ovarian follicles and therefore can be used for the evaluation of the ovarian reserve function and the prediction of ovary ageing and ovarian response during in vitro fertilization (IVF) treatment. This article summarizes the clinical application of AMH, especially in evaluating ovarian reserve functions.
Anti-Mullerian Hormone ; blood ; Biomarkers ; blood ; Female ; Fertilization in Vitro ; Follicle Stimulating Hormone ; blood ; Humans ; Ovarian Follicle ; physiology ; Ovarian Hyperstimulation Syndrome ; prevention & control ; Ovary ; physiology ; Polycystic Ovary Syndrome ; blood

Melatonin (N-acetyl-5-methoxytryptamine, MT) is a hormone synthesized and secreted by the pineal gland. Recent studies show that melatonin plays an essential role in the pathogenesis of many reproductive processes. High-concentration melatonin exists in human preovulatory follicular fluid and melatonin receptors are present in ovarian granulosa cells, which indicates the direct effects of melatonin on ovarian function. Reactive oxygen species are involved in a number of reproductive events, including folliculogenesis, follicular atresia, ovulation, oocyte maturation, and corpus luteum formation. Melatonin and its metabolites, as powerful antioxidants and free radical scavengers, can potentially inhibit premature ovarian failure. Literature published in recent years shows the essential roles of melatonin in improving human ovarian function and oocyte quality as well as in the management of infertility. Researches on the action mechanisms of melatonin may provide a theoretical basis for the prevention and treatment of some clinical diseases.
Female ; Granulosa Cells ; metabolism ; physiology ; Humans ; Melatonin ; metabolism ; physiology ; Ovarian Follicle ; growth & development ; metabolism ; Ovary ; physiology ; Reactive Oxygen Species ; metabolism

Melatonin,an endocrine hormone synthesized by the pineal gland,plays an important role in the reproduction.The growth and development of follicles is the basis of female mammalian fertility.Follicles have a high concentration of melatonin.Melatonin receptors exist on ovarian granulosa cells,follicle cells,and oocytes.It regulates the growth and development of these cells and the maturation and atresia of follicles,affecting female fertility.This paper reviews the protective effects and regulatory mechanisms of melatonin on the development of ovarian follicles,granulosa cells,and oocytes and makes an outlook on the therapeutic potential of melatonin for ovarian injury,underpinning the clinical application of melatonin in the future.
Animals ; Female ; Melatonin/pharmacology* ; Ovarian Follicle ; Oocytes ; Granulosa Cells/physiology* ; Mammals

Little is known about the factors that control the initiation of growth of primordial follicles. The objective of the present study was to investigate the effect of c-erbB₂ on the onset of primordial follicle development, and whether c-erbB₂ mediates the effect of epidermal growth factor (EGF) in this process. We synthesized three pairs of siRNAs targeting the c-erbB₂ mRNA and transferred them into the newborn rat ovary cultured in vitro with Metafectene. After siRNAs transfection, the efficiency of siRNAs was tested by examining c-erbB₂ mRNA and protein levels. The level of c-erbB₂ mRNA was reduced by 49.6%, 46.7% and 82.6% respectively after transfecting siRNA1, siRNA2 and siRNA3, and the level of ErbB₂ protein also reduced remarkably after siRNA3 transfection. c-erbB₂ siRNA3 significantly inhibited the primordial follicle initiation and development; EGF augmented primordial follicles formation, but the effect was abolished by c-erbB₂ siRNA3. All of these results suggest that c-erbB₂ plays an important role in primordial follicle development and folliculogenesis initiation, and mediates the effect of EGF on primordial follicle development.
Animals ; Animals, Newborn ; Female ; Organ Culture Techniques ; Ovarian Follicle ; growth & development ; RNA, Small Interfering ; Rats ; Receptor, ErbB-2 ; physiology

OBJECTIVE: To determine the copy number of granular cell mitochondria DNA (mtDNA) and deletion of 4 977 bp in patients with diminished ovarian reserve (DOR) to primarily study the structural integrity of granular cell mtDNA. METHODS: We selected 50 DOR patients and 50 patients with normal ovarian reserve (NOR). Granular cells in liquor folliculi of these patients were collected at ovum pick-up day. DNA was extracted from the granular cells. The mtDNA 4 977 bp deletion of granular cells was detected by PCR and the number of granular cells mtDNA copies was detected by real-time PCR. RESULTS: No 4 977 bp deletion of ovary granular cell mitochondria DNA in the 100 patients was detected. There was no significant difference in the relative quantity of granular cell mitochondria DNA in the DOR group and the NOR group. CONCLUSION The structure of granular cells mtDNA in DOR patients is complete and granular cells may be used as donor cells for DOR patients plasma autologous transplants mitochondorial.
Adult ; Case-Control Studies ; DNA, Mitochondrial ; genetics ; Female ; Fertilization ; Granulosa Cells ; metabolism ; Humans ; Infertility, Female ; genetics ; Oocytes ; physiology ; Ovarian Diseases ; genetics ; Ovarian Follicle ; cytology ; Ovary ; physiopathology ; Sequence Deletion

BACKGROUNDIt is believed that estrogen plays pivotal roles in the regulation of follicle/oocyte maturation and oocyte fertilizability. It is also involved in the functional preparation of the fallopian tubes for subsequent gamete interaction, in early embryonic development occurring in the tubal microenvironment, and in the preparation of the uterus for implantation. This study was designed to determine whether estrogen is required for follicular and embryonic development.

METHODSThe biosynthesis of estrogen was blocked by a daily injection of the aromatase inhibitor, Arimidex, at a dose of 100 micro g/d, using 3 - 4 week old C57B6 F1 female mice. Injections were continued for 3 days in experiment 1 (n = 10) and for 5 days in experiment 2 (n = 23). Mice in the control group (n = 27) were given the same amount of saline. Exogenous gonadotrophin [7.5 IU pregnant mare serum gonadotrophin (PMSG)] was administered to induce follicular growth and development on the second day. In experiment 1, we tested estrogen and progesterone levels and examined ovary morphology two days later. In experiment 2, 47 hours after PMSG injection, 5 IU human chorionic gonadotropin (hCG) was given and two female mice were then caged with a male mouse overnight. Two days later, we measured estrogen and progesterone levels. We then removed the embryos, cultured them, and examined embryonic development every 24 hours for 3 days.

RESULTSBefore hCG injection, estrogen levels in mice from the Arimidex group were suppressed by 94%, and progesterone levels were suppressed by 75%. There was no difference between the two groups in mean number of total follicles found per animal (30.4 follicles/animal in the control group and 27 follicles/animal in the Arimidex group). Two days after hCG injection, estrogen levels in the Arimidex group were significantly lower than that in the control group (P < 0.01), while progesterone levels were not significantly lower (P > 0.05). The rate of development of embryos, morulae, blastocysts, and hatching blastocysts was not significantly different between the two groups (P = 0.20, 0.10, 0.44, and 0.38, respectively).

CONCLUSIONSIn the present study, by depriving mice of normal estrogen support, we have been able to rule out the absolute need for rising levels of estrogen for the completion of the follicular maturation process and the development of embryos in vitro.

Animals ; Chorionic Gonadotropin ; pharmacology ; Embryonic and Fetal Development ; Estrogens ; physiology ; Female ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Nitriles ; pharmacology ; Oocytes ; physiology ; Ovarian Follicle ; physiology ; Pregnancy ; Triazoles ; pharmacology

OBJECTIVETo investigate the relationship between fetal growth restriction and decreased ovarian reserve (DOR) in adulthood to screen high-risk population for early interventions.

METHODSForty-four patients with FGR and 88 normal women aged 18-40 years were enrolled. All the subjects were examined for serum levels of follicle-stimulating hormone (FSH), inhibin B (INH-B), and anti-mullerian hormone (AMH) using enzyme-linked immunosorbent assay method in the first 3-5 days of the menstrual cycle, and the counts of antrum ovarian follicle were detected by transvaginal or transabdominal ultrasonography.

RESULTSThe serum levels FSH, INHB, AMH, and AFC in FGR group differed significantly from those in the control group (P<0.05).

CONCLUSIONFGR will affect reproductive endocrine function in adulthood to cause a decreased ovarian reserve.

Adolescent ; Adult ; Anti-Mullerian Hormone ; blood ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Fetal Growth Retardation ; Follicle Stimulating Hormone ; blood ; Humans ; Inhibins ; blood ; Menstrual Cycle ; Ovarian Follicle ; physiology ; Ovarian Reserve ; Prospective Studies ; Young Adult

PURPOSE: To investigate the direct relationship between the follicular fluid (FF) level of soluble human leukocyte antigen G (HLA-G) and fertilizability of the corresponding oocyte as well as the morphological quality of the corresponding embryo. MATERIALS AND METHODS: Sixty-three patients were stimulated with recombinant FSH combined with gonadotropin-releasing hormone (GnRH) agonist long (n=5) or antagonist protocol (n=58) for standard in vitro fertilization (IVF). At the time oocyte retrieval, follicular fluid was obtained from single dominant follicle in 63 patients, and the level of soluble HLA-G was measured by sandwich enzyme-liked immunosorbent assay (ELISA). Normal fertilization and individual embryo quality were evaluated, and were graded to four categories by morphological criteria (the embryo with symmetrical blastomeres and no fragmentation were assigned as grade A). Good-quality embryo was defined as those with grade A or B. RESULTS: Soluble HLA-G was not detected in 15 FF samples. In the group with positive FF soluble HLA-G (sHLA-G) (n=48), high levels of sHLA-G (>117.758 U/mL) could predict the failure of fertilization with statistical significance {area under the curve (AUC) 0.676, 95% confidence interval (CI) 0.525-0.804}. However, the FF sHLA-G level was not related with the formation of good-quality embryo. CONCLUSION: High level of FF sHLA-G could predict the fertilization failure of the corresponding oocyte, but was not related with the formation of good-quality embryo.
Adult ; Enzyme-Linked Immunosorbent Assay ; Female ; Follicular Fluid/*metabolism ; HLA-G Antigens/*metabolism ; Humans ; Oocytes/*cytology/physiology ; Ovarian Follicle/*cytology/physiology