The normal development of follicles involves a series of complex life processes such as ordered transcriptional activation and inhibition, which is crucial for female reproductive ability. Histone methylation can change the chromatin state in cells and affect the transcription activity of genes. Current studies indicate that epigenetic modifications such as histone methylation play an important regulatory role in follicular development in female mammals. This paper summarized the relationship between H3K4, H3K9 methylation and germ cell development, their regulatory effects, including their dynamical changes during follicular development, and the progress of H3K4me3 and other histone methylation binding to promoter regions of different genes to regulate gene expression and thus affect germ cell epigenetic reprogramming, oocyte transcription, meiosis and other processes. This review will provide a reference for the study of mechanisms related to histone methylation modification and the development and maturation of gonadal parenchymal cells.
Animals ; DNA Methylation ; Epigenesis, Genetic ; Female ; Histones ; Mammals ; Ovarian Follicle/growth & development* ; Protein Processing, Post-Translational

The growth and development of follicles are regulated by genes,hormones and growth factors autocrined and paracrined from granulosa cells,theca cells,and oocytes.Products of glycolysis from granulosa cells such as pyruvate and lactate are one of the main energy sources,which play an important role during folliculogenesis and follicle maturity.Studies on the changes of the products and rate-limiting enzymes during granulosa cells' glycolysis help to clarify the molecular mechanism of energy demand in folliculogenesis and guide the clinical treatment of infertility due to abnormal follicular development.This article reviews recent research advances in the energy demand and regulatory mechanism in different states of folliculogenesis.
Energy Metabolism ; Female ; Glycolysis ; Granulosa Cells ; Humans ; Intercellular Signaling Peptides and Proteins ; Oocytes ; Ovarian Follicle ; growth & development ; Theca Cells

The aim of the present study was to explore the effect and mechanism of Bushen Huoxue recipe (BHR) on ovarian reserve in mice with premature ovarian failure (POF). Mice were divided into 3 groups: normal group, model group and BHR group. Intraperitoneal injection of cyclophosphamide was performed to create the POF model. Primordial follicular (PDF) number, ovarian wet weight, ovarian index, and estrous cycle were analyzed to evaluate the effect of BHR on POF. Meanwhile, the mRNA and protein level of Mouse Vasa Homologue (MVH) in the bone marrow, peripheral blood and ovary were detected, to explore the underlying mechanism of the treatment efficacy of BHR on ovarian reserve. By the time of BHR treatment for 28 days, BHR increased the PDF number and shortened the estrous cycle of POF mice. BHR also decreased the mRNA level of MVH in the bone marrow, and increased mRNA and protein level of MVH in the ovary of POF mice. Our results demonstrated a treatment efficacy of BHR on POF mice, and revealed that BHR might repair the dysfunction of germline stem cells in the bone marrow, and thus to improve the ovarian reserve and enhance the ovarian function of POF mice through neo-oogenesis.
Animals ; Bone Marrow ; drug effects ; metabolism ; Cyclophosphamide ; toxicity ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Estrous Cycle ; drug effects ; Female ; Gene Expression Regulation ; drug effects ; Humans ; Mice ; Ovarian Follicle ; drug effects ; growth & development ; Ovarian Reserve ; drug effects ; Primary Ovarian Insufficiency ; chemically induced ; drug therapy ; pathology

The effect of high concentrations of testosterone on ovarian follicle development was investigated. Primary follicles and granulosa cells were cultured in vitro in media supplemented with a testosterone concentration gradient. The combined effects of testosterone and follicle-stimulating hormone (FSH) on follicular growth and granulosa cell gonadotropin receptor mRNA expression were also investigated. Follicle growth in the presence of high testosterone concentrations was promoted at early stages (days 1-7), but inhibited at later stage (days 7-14) of in vitro culture. Interestingly, testosterone-induced follicle development arrest was rescued by treatment with high concentrations of FSH (400 mIU/mL). In addition, in cultured granulosa cells, high testosterone concentrations induced cell proliferation, and increased the mRNA expression level of FSH receptor (FSHR), and luteinized hormone/choriogonadotropin receptor. It was concluded that high concentrations of testosterone inhibited follicle development, most likely through regulation of the FSH signaling pathway, although independently from FSHR downregulation. These findings are an important step in further understanding the pathogenesis of polycystic ovary syndrome.
Androgens ; pharmacology ; Animals ; Cell Proliferation ; drug effects ; Female ; Follicle Stimulating Hormone ; genetics ; metabolism ; pharmacology ; Gene Expression Regulation, Developmental ; Granulosa Cells ; cytology ; drug effects ; metabolism ; Mice ; Ovarian Follicle ; cytology ; drug effects ; growth & development ; metabolism ; Primary Cell Culture ; RNA, Messenger ; genetics ; metabolism ; Receptors, FSH ; genetics ; metabolism ; Receptors, Gonadotropin ; genetics ; metabolism ; Receptors, LH ; genetics ; metabolism ; Signal Transduction ; drug effects ; genetics ; Testosterone ; antagonists & inhibitors ; pharmacology

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

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

In mammals, ovarian follicle is made of an oocyte with its surrounding granulosa cells and theca cells. Follicular growth and development is a highly coordinated programmable process, which guarantees the normal oocyte maturation and makes it having the fertilizing capacity. The paracrine and autocrine between oocytes and granulosa cells are essential for the follicular development to provide a suitable microenvironment. Phosphatidylinositol-3 kinase /protein kinase B is one of these important regulatory signaling pathways during this developmental process, and bone morphogenetic protein-15 an oocyte-specific secreted signal molecule, which regulates the follicular development by paracrine in the mammalian ovary. The present article overviewed the role of phosphatidylinositol-3 kinase / protein kinase B signaling during the follicular development based on our previous investigation about protein kinase B /forkhead transcription factor forkhead family of transcription factors -3a, and then focused on the regulatory effects of bone morphogenetic protein-15, as a downstream signal molecule of phosphatidylinositol-3 kinase / forkhead family of transcription factors -3a pathway, on ovarian follicular development, which helped to further understand the molecular mechanism regulating the follicular development and to treat ovarian diseases like infertility.
Animals ; Bone Morphogenetic Protein 15 ; physiology ; Female ; Granulosa Cells ; physiology ; Humans ; Mammals ; Ovarian Follicle ; growth & development ; Ovary ; growth & development ; Phosphatidylinositol 3-Kinase ; physiology ; Proto-Oncogene Proteins c-akt ; physiology ; Signal Transduction

OBJECTIVETo observe clinical efficacy of plum-blossom needle for follicular maldevelopment (FM).

METHODSFifty cases of FM were randomly divided into a plum-blossom needle group and a medication group, 25 cases in each one. In the plum-blossom needle group, the plum-blossom needle was applied along Thoroughfare, Conception, Governor and Belt Vessel as well as at Pishu (BL 20), Weishu (BL 21), Shenshu (BL 23), Luanchao (Extra), Zigong (EX-CA 1) during the follicular growth phase, once every other day. In the medication group, clomifene (CC) was prescribed for oral administration and human choriogonadotropin (HCG) was given by intramuscular injection, once each day. For both groups, one menstrual cycle constituted one course. After two courses of treatment, follicular development condition, the changes of endometrial thickness and morphology, ovarian resistent index (RI) and pulsatility index (PI), rate of ovulation and pregnancy were compared between the two groups.

RESULTSAfter the treatment, the average diameters of the biggest follicle increased in both groups, while the endometrial thickness and morphology in the plum-blossom needle group were superior to those in the medication group (all P < 0.05). Ovarian RI and PI during mature follicular phase in the plum-blossom needle group were inferior to those in the medication group (both P < 0.05). The differences in ovulation and pregnancy rate were not significant statistically between the two groups (both P > 0.05).

CONCLUSIONThe plum-blossom needle therapy based on regulating Thoroughfare, Conception, Governor and Belt Vessel could improve the ovarian blood perfusion, promote the follicular growth, increase the ovulation rate of mature follicle and avoid the out-of-sync between growth of follicle and endometrium during the treatment of western medication.

Acupuncture Therapy ; Adult ; Clomiphene ; therapeutic use ; Female ; Humans ; Needles ; Ovarian Diseases ; drug therapy ; physiopathology ; therapy ; Ovarian Follicle ; growth & development ; Young Adult

OBJECTIVE: To determine whether animal age impacts in vitro preantral follicle growth. Effects of hCG, stem cell factor (SCF), and/or insulin-like growth factor (IGF) supplementation in growth medium were also investigated. METHODS: Intact preantral follicles were mechanically isolated from fresh ovaries of BDF1 mice and cultured in growth medium for 9 to 11 days. Surviving follicles with antrum formation were transferred to maturation medium for 14 to 18 hours. Follicle survival, antrum formation, and retrieval of metaphase II (MII) oocytes were compared among three age categories (4-5, 7-8, and 10-11 week-old). By using 7- to 8-week-old mice, preantral follicles were cultured in growth medium supplemented with hCG (0, 5, or 10 mIU/mL), SCF (50 ng/mL), IGF-1 (50 ng/mL), and SCF+IGF-1. RESULTS: Seven- to eight-week-old mice showed a higher follicle survival and antrum formation and produced more MII oocytes compared to other groups. In the 7- to 8-week-old mice, supplementation of 5 mIU/mL hCG significantly enhanced the antrum formation but the percentage of MII oocytes was similar to that of the control. Supplementation of SCF+IGF-1 did not enhance follicle survival or antrum formation but the percentage of MII oocytes increased modestly (39.1%) than in the control (28.6%, statistically not significant). CONCLUSION: Seven- to eight-week-old mice showed better outcomes in growth of preantral follicles in vitro than 4- to 5- or 10- to 11-week-old mice. Supplementation of hCG enhanced antrum formation and supplementation of SCF+IGF-1 yielded more mature oocytes; hence, these should be considered in the growth of preantral follicles in vitro.
Animals ; Female ; Humans ; Insulin-Like Growth Factor I ; Metaphase ; Mice ; Oocytes ; Ovarian Follicle ; Ovary ; Stem Cell Factor ; Stem Cells

OBJECTIVETo observe the effect of ultrasound stimulation at the acupoint Guanyuan (CV 4) on follicular development in menopausal rats.

METHODSMenopausal female SD rats were selected by vaginal smear examinations. The rats were subjected to ultrasound stimulation at the acupoint Guanyuan with the output power of 0.1 W, working frequency of 9 MHz, and focal length of 4.5-5 mm. Electrochemiluminescence immunoassay was used to detect the serum estrogen levels of the menopausal rats. The changes in the ovarian tissue histology and the follicle number were observed.

RESULTSCompared with the control group, a 10-day ultrasound stimulation for 10 and 5 min daily at Guanyuan significantly increased the serum estrogen levels and the numbers of primary and secondary follicles (P<0.05) and reduced the number of atretic follicles in the menopausal rats (P<0.05).

CONCLUSIONUltrasound stimulation at the acupoint Guanyuan can increase the estrogen secretion function and promote the development of follicles in menopausal rats.

Acupuncture Points ; Animals ; Estrogens ; blood ; Female ; Menopause ; Ovarian Follicle ; growth & development ; Rats ; Rats, Sprague-Dawley ; Sonication