Research Progress in the Regulation of Follicle Development by Melatonin / 中国医学科学院学报

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.

Effect of electroacupuncture at different acupoints on follicle development and related factors in serum and ovary tissues of PCOS rats / 针刺研究

OBJECTIVE: To observe the effect of electroacupuncture (EA) at different acupoints on follicle development, expression of gonadotropins and their receptors and anti-Müllerian hormone(AMH), inhibin B(INHB) in polycystic ovarian syndrome (PCOS) rats, so as to explore its mechanisms underlying improvement of PCOS. METHODS: Sixty female SD rats were randomized into six groups: control, model, Zusanli(ST36), Sanyinjiao(SP6), Guanyuan(CV4) and combination (ST36+SP6+CV4, n=10 rats/group). The PCOS model was established by gavage of Letrozole solution (1.0 mg/kg) once daily for 21 consecutive days. Rats of the control group were given 1% Carboxymethyl Cellulose (CMC, 1 mg/kg). EA (2 Hz) was applied to ST36, SP6, or/and CV4 for 20 min, once daily for 14 consecutive days. The number of follicles was counted, and the ovarian structure and follicular development were observed under light microscope after H.E. stain, and the contents of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), AMH, and INHB were assayed by enzyme-linked immunosorbent assay, and the ratio of LH/FSH was calcula-ted. The immunoactivity of LH receptor (LHR) and FSH receptor (FSHR) proteins was detected by immunohistochemistry. RESULTS: After modeling, the number of follicles at the growth stage, contents of serum LH, AMH and INHB, and ratio of LH/FSH were significantly increased, and serum FSH level and FSHR, LHR immunoactivity were remarkably decreased in the model group relevant to the control group (P0.05). CONCLUSION: EA of CV4, SP6, ST36 and ST36+CV4+SP6 can reduce the number of follicles at the growth stage and regulate the expression levels of gonadotropins in PCOS rats. The effects of EA of CV4 and ST36 are evidently better than those of EA of SP6 in up-regulating serum FSH content and in down-regulating LH/FSH ratio, and serum AMH and INHB levels, and EA of SP6 is evidently superior to EA of CV4 down-regulating LH level, but without synergistic effect among the 3 acupoints.

Loss-of-function of sox3 causes follicle development retardation and reduces fecundity in zebrafish

Folliculogenesis is essential for production of female gametes in vertebrates. However, the molecular mechanisms underlying follicle development, particularly apoptosis regulation in ovary, remain elusive. Here, we generated sox3 knockout zebrafish lines using CRISPR/Cas9. sox3 knockout led to follicle development retardation and a reduced fecundity in females. Comparative analysis of transcriptome between sox3 and wild-type ovaries revealed that Sox3 was involved in pathways of ovarian steroidogenesis and apoptosis. Knockout of sox3 promoted follicle apoptosis and obvious apoptosis signals were detected in somatic cells of stages III and IV follicles of sox3 ovaries. Moreover, Sox3 can bind to and activate the promoter of cyp19a1a. Up-regulation of Cyp19a1a expression promoted 17β-estradiol synthesis, which inhibited apoptosis in follicle development. Thus, Sox3 functions as a regulator of Cyp19a1a expression, via 17β-E2 linking apoptosis suppression, which is implicated in improving female fecundity.

Effect of miR-125b on dermal papilla cells of goat secondary hair follicle

Background: MicroRNAs (miRNAs) are endogenous noncoding RNAs that regulate various biological processes. miR-125b is a miRNA that has been reported to be critical for hair follicle (HF) morphogenesis and development. We identified that the expression of miR-125b varies during an individual hair cycle (anagen, catagen, and telogen) in the skin of cashmere goats. We constructed a gain model (by overexpressing miR-125b) and a loss model (by inhibiting endogenous miR-125b) based on dermal papilla cells (DPCs) to further investigate the role of miR-125b in HF cycle. In addition, we used a dual-luciferase system to highlight the predicated target genes of miR-125b. Results: We found that miR-125b affects the expression of FGF5, IGF-1, SHH, TNF-α, MSX2, LEF-1, FGF7, NOGGIN, BMP2, BMP4, TGF-ß1, and ß-catenin. The dual-luciferase assay further validated a direct interaction between miR-125b and FGF5 and TNF-α. Conclusion: miR-125b affects the expression levels of genes related to hair cycle and may also play a critical role in regulating the periodic development of HF.

Expressions of ovarian function-related proteins in ovarian follicles in different development stages and their significances / 吉林大学学报(医学版)

Objective:To detect the expressions of ovarian function-related proteins in the ovarian follicles in different development stages,and to explore their roles and significances in the regulation of follicular development and ovarian function. Methods:The ovarian tissue containing primordial,primary,secondary follicles,mature follicles, atretic follicles and corpus albicans of the woman in the childbearing age was selected. Immunohisto chemical analysis was used to detect the expressions of Glyoxal enzyme I (glyoxalase I),ubiquitin carboxy-terminal hydrolase L1 (UCH-L1),heat shock protein 27 (HSP27),serum amyloid P (SAP)proteins in the ovarian follicles in different stages.The expression intensities of these proteins were compared.Results:The expression intensities of Glyoxalase I and UCH-L1 in the granulosa cells and theca cells of secondary follicles and marure follicles were strong,which were higher than those in the cytoplasm of primordial and primary follicles.The expression intensities of HSP27 in the cytoplasm of primordial and primary follicles were strong,which were higher than those in the granulosa cells and theca cells of secondary follicles and marure follicles.The expression intensities of Glyoxalase I and HSP27 in the atretic follicles were strong,which were higher than that in the growth follicles. The expressions of SAP were positive in the primordial,primary follicles,secondary and mature follicles and the expression intensities were not different.The expressions of four proteins in the corpus albicans did not express. Conclusion:The high expression of UCH-L1 and low expression of HSP27 are associated with the mature and development of follicles;the high expressions of Glyoxalase I and HSP27 are associated with the follicular atresia and ovarian failure.

Comparison of early developmental differences of hair follicles in different skin areas of neonatal mice / 中国实验动物学报

Objective The aim of this study was to observe the growth difference and expression of cytochrome C of skin hair follicles in neonatal mice .Methods The morphology of different skin hair follicles of neonatal mice ( postnatal day 1-9)were observed by HE staining histology and cytochrome C was detected by immunohistochemistry .Results The skin hair follicles in different parts of neonatal mice showed differences not only in morphology but also in developmental pe -riods.Hair follicle growth in the back and tail skin had a nonlinear and growing period .After the nonlinear and growing pe-riod they began to grow rapidly .The tail development was slightly slower than that on the back .The hair follicles of vibris-sae were very special , and started to develop without a stable period .Conclusions The results of morphological observa-tion and cytochrome C immunohistochemistry demonstrate that differences exist in the hair follicle morphology and develop -mental times in the skin of different parts of the body in neonatal mice .

Expression of Apoptosis Gene Bok in the Rat Ovary / 대한산부인과학회잡지

OBJECTIVE: Bok, Bcl-2-related ovarian killer, is a proapoptotic Bcl-2 family protein identified in the ovary based on its dimerization with the antiapoptotic protein Mcl-1. The present study examined the hormonal regulation and localization of Bok messenger RNA levels in the rat ovary during the follicle development. METHODS: We used the female rats of SD strain. Bok mRNA levels in the ovary were determined by Northern blot analysis. In situ hybridization were performed to determine the specific ovarian cell type expressing Bok mRNA. RESULTS: Northern blot analysis of ovaries obtained from immature rats revealed increasing levels of Bok mRNA during postnatal development. The major cell types expressing Bok mRNA were the granulosa cells of preantral and atretic follicles. Treatment of immature rats with diethylstilbestrol (DES) for 24-48 h increased ovarian Bok mRNA levels. Bok mRNA was remained the same levels in rats removed DES for 24- 48 h to induce apoptosis. High signals of Bok mRNA after DES treatment were detected in granulosa cells of early antral follicles. Treatment of immature rats with pregnant mare's serum gonadotropin (PMSG) for 12 h increased markedly ovarian Bok mRNA expression which was detected mainly in preantral and atretic follicles. Interestingly, low levels of Bok mRNA were also expressed in granulosa cells of preovulatory follicles. Treatment of PMSG-primed rats with human chorionic gonadotropin (hCG) stimulated strongly ovarian Bok mRNA expression at 6-9 h. At that time, Bok mRNA was expressed in granulosa cells of atretic and small growing follicles. In adult estrus cyclic ovaries, Bok gene expression was higher on proestrus and estrus than metaestrus and diestrus. Moreover, the highly increased expression of Bok mRNA was found in rat ovaries at 48 h after hypophysectomy. CONCLUSION: These results demonstrate that Bok is one of proapoptotic Bcl-2 members expressed in early growing and atretic follicles during the ovarian follicular development. Gonadotropins induce a transient increase of Bok gene expression in granulosa cells of preantral and preovulatory follicles indicating some role in the ovulatory process.