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
Yuxun Zhou, Wangsheng Zhu, Zhengxia Guo, Ying Zhao, Zijun Song and Junhua Xiao
The timing of puberty is a complex trait which is regulated by environmental and genetic factors, but the detailed regulatory mechanism remains elusive. Maternal nutrition administration during late gestation in rats revealed that the time of onset of puberty in daughter rats was influenced by the mother’s nutritional and physiological status during the embryonic development period. In this study, the potential effects of the maternal nuclear genome on the timing of puberty of offspring were investigated. Two inbred strains of mice (C3H/HeJ (C3H) and C57BL/6J (B6)) were used to set up two pedigrees (direct and reciprocal crosses), and the timing of puberty in all these mice (parent, F1 and F2) was recorded (the females were assessed by vaginal opening (VO) and the males by balano preputial separation (BPS)). The results from data of 822 mice showed that: 1) in female mice, the heritability of the timing of puberty in direct and reciprocal crosses is 68.51% and 63.97% respectively; 2) in female mice, a significant difference in the timing of puberty is observed between B6 and C3H (P = 3.7 × 10−13) mice as well as between direct and reciprocal F1 hybrids (P = 5.4 × 10−3), but not between direct and reciprocal F2 hybrids (P = 0.0941); 3) in male mice, direct and reciprocal F1 hybrids differ significantly from each other in the timing of BPS (P = 2.7 × 10−7), while such differences vanish in their male progenitor and progeny. The significant discrepancy between direct and reciprocal crosses in F1 but not in either cross of F2 hybrids reveals that the maternal nuclear genome has effects on the timing of puberty in mice progeny, probably through imprinting genes or the genes associated with intra-uterine physiological status.