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Tea is the most consumed beverage in the world. Tea polyphenols are the major constituents of tea leaves and have shown many potential healthy benefits. However, whether tea polyphenols influence ovarian follicle assembly and development and ovarian life span is unknown. To study the effect of tea polyphenols on ovarian follicle development and oocyte apoptosis, we investigated rat ovarian development of different ages [from postnatal day (PD)1 after birth to 10 months] after treatment with tea polyphenols. Our data showed that the percentage of unassembled follicles increased in the ovaries of 1- and 2-day-old rats which were ip injected with tea polyphenols (50 mg/kg/d) or whose mothers were treated with tea polyphenols (100 mg/kg/d) by intragastric administration from the day 11 after the detection of vaginal plug till delivery. The percentage of primordial follicles increased, while that of developing follicles decreased in the ovaries of 4- and 8-day-old rats following peritoneal injection with tea polyphenols compared with controls. The ratio of terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL)-positive oocytes decreased in the ovaries of neonatal rats following tea polyphenol treatment. In the 3- and 10-month-old rat ovaries, the number of primordial follicles augmented, whereas that of atretic follicles decreased after the treatment for 4 weeks. These data suggest that tea polyphenols may inhibit the transition from primordial to developing follicles, extend the entire growth phase of a follicle, and reduce dominant follicle numbers per cycle to increase the reserve of germ cells, inhibit oocyte apoptosis and follicle atresia during ovarian development from birth to early aged, and retard climacterium in rats. Drinking even a small cup of tea per day may benefit to extent the productive life of ovary.

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Background Maternal obesity impairs embryonic developmental potential and significantly increases the risks of metabolic disorders in offspring. However, the epigenetic transmission mechanism of maternal metabolic abnormalities is still poorly understood. Methods We established an obesity model in female mice by high-fat diet (HFD) feeding. The effects of the HFD on the developmental potential of oocytes and embryos, the metabolic phenotype, and epigenetic modifications were investigated. The efficacy of metformin administration was assessed. Finally, the regulatory pathway of epigenetic remodeling during zygotic genome activation (ZGA) was explored. Results Maternal HFD consumption significantly impaired glucose tolerance and increased the risk of metabolic disorders in F0 and F1 mice. Maternal HFD consumption also decreased embryonic developmental potential, increased reactive oxygen species (ROS) and γH2AX levels, and reduced the mitochondrial membrane potential (MMP) within oocytes, causing high levels of oxidative stress damage and DNA damage. Starting with this clue, we observed significantly increased RIF1 levels and shortened telomeres in obese mice. Moreover, significant abnormal DNA methylation and histone modification remodeling were observed during ZGA in obese mice, which may be coregulated by RIF1 and the ZGA marker gene MuERV-L. Metformin treatment reduced RIF1 levels, and partially improved ZGA activation status by rescuing epigenetic modification remodeling in oocytes and preimplantation embryos of obese mice. RIF1 knockdown experiments employing Trim-Away methods showed that RIF1 degradation altered the H3K4me3 and H3K9me3 enrichment and then triggered the MuERV-L transcriptional activation. Moreover, ChIP-seq data analysis of RIF1 knockouts also showed that RIF1 mediates the transcriptional regulation of MuERV-L by changing the enrichment of H3K4me3 and H3K9me3 rather than by altered DNA methylation. Conclusion Elevated RIF1 in oocytes caused by maternal obesity may mediate abnormal embryonic epigenetic remodeling and increase metabolic risk in offspring by regulating histone modifications on MuERV-L, which can be partially rescued by metformin treatment.

Gonadotrophin-releasing hormone (GnRH) agonists (GnRHa) have been widely used to induce a state of downregulation for in vitro fertilization, and its direct effects on the pituitary are well known. However, the effects of GnRHa on the expression of anti-mullerian hormone (AMH) by follicles in varying stages in vivo remain to be fully elucidated. In the present study 84 cyclic mice were randomly divided equally into four GnRHa groups and three cyclic mice were used as a control group. The expression levels of AMH in follicles of varying stages between days 0 and 7 following GnRHa administration were quantified using immunohistochemistry. The expression of AMH in follicles at various stages revealed dynamic changes during the process of downregulation. AMH in primary follicles initially increased and then decreased gradually. In small and large preantral follicles and in granulosa cells (GCs) surrounding the oocyte of small antral follicles, the expression of AMH began to increase on day 1, was attenuated on day 2, and then increased to a peak. The expression levels of AMH in the GCs surrounding the basement membrane, in contrast to the GCs surrounding the oocyte, were significantly lower and did not increase on day 1. In all stages of follicles, the expression of AMH declined gradually between the peak level and last day of downregulation. On day 7, the varying follicular stages all expressed lower levels of AMH than on day 0. This decrease was more prominent in the higher dose groups, compared with the lower dose groups. In conclusion, GnRHa was observed to induce time-dependent changes in the expression of AMH at varying follicular stages, which occurred in a dose-dependent manner.