Puberty onset is a complex trait regulated by multiple genetic and environmental factors. In this study, we narrowed a puberty-related QTL region down to a 1.7 Mb region on chromosome X in female mice and inferred miR-505-3p as the functional gene. We conducted ectopic expression of miR-505-3p in the hypothalamus of prepubertal female mice through lentivirus-mediated orthotopic injection. The impact of miR-505-3p on female puberty was evaluated by the measurement of pubertal/reproduction events and histological analysis. The results showed that female mice with overexpression of miR-505-3p in the hypothalamus manifested later puberty onset timing both in vaginal opening and ovary maturation, followed by weaker fertility lying in the longer interval time between mating and delivery, higher abortion rate and smaller litter size. We also constructed miR-505-3p-knockout mice by CRISPR/Cas9 technology. miR-505-3p-knockout female mice showed earlier vaginal opening timing, higher serum gonadotrophin and higher expression of puberty-related gene in the hypothalamus than their WT littermates. Srsf1 proved to be the target gene of miR-505-3p that played the major role in this process. The results of RNA immunoprecipitation sequencing showed that SRSF1 (or SF2), the protein product of Srsf1 gene, mainly bound to ribosome protein (RP) mRNAs in GT1-7 cells. The collective evidence implied that miR-505-3p/SRSF1/RP could play a role in the sexual maturation regulation of mammals.
Yuxun Zhou, Li Tong, Maochun Wang, Xueying Chang, Sijia Wang, Kai Li and Junhua Xiao
Tong Sun, Wen-Bo Deng, Hong-Lu Diao, Hua Ni, Yu-Yan Bai, Xing-Hong Ma, Li-Bin Xu and Zeng-Ming Yang
Prostaglandin (PGE) 2 is the most common prostanoid and plays an important role in female reproduction. The aim of this study was to examine the expression and regulation of microsomal (m) PGE synthase (PGES)-1 and cytosolic (c) PGES in the mouse ovary during sexual maturation, gonadotropin treatment and luteal development by in situ hybridization and immunohistochemistry. Both mPGES-1 mRNA signals and immunostaining were localized in the granulosa cells, but not in the thecal cells and oocytes. cPGES mRNA signals were localized in both granulosa cells and oocytes, whereas cPGES immunostaining was exclusively localized in the oocytes. In our superovulated model of immature mice, there was a basal level of mPGES-1 mRNA signals in the granulosa cells at 48 h after equine chorionic gonadotropin (eCG) treatment. mPGES-1 mRNA level was induced by human chorionic gonadotropin (hCG) treatment for 0.5 h, whereas mPGES-1 immunostaining was slightly induced at 0.5 h after hCG treatment and reached a maximal level at 3 h after hCG treatment. eCG treatment had no obvious effects on either cPGES mRNA signals or immunostaining. A strong level of cPGES immunostaining was present in both unstimulated and eCG-treated groups. Both mPGES-1 mRNA signals and immunostaining were highly detected in the corpus luteum 2 days post-hCG injection and declined from days 3 to 7 post-hCG injection. cPGES immunostaining was at a basal level or not detectable from days 1 to 7 after hCG injection and was highly expressed in the corpus luteum from days 9 to 15 post-hCG injection. PGE2 biosynthesized through the mPGES-1 pathway may be important for follicular development, ovulation and luteal formation.