miR-505-3p is a repressor of puberty onset in female mice

Abstract

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.

Oocyte Maturation and miRNAs: Studying a Complicate Interaction to Reveal Possible Biomarkers for Female Infertility

“…The up-regulation of miR-505-3p in the group of poor oocyte quality is possibly related to infertility. Its over-expression in mice was associated with delayed ovary maturation and lower fertility [ 44 ]. However, Barragán and colleagues, by examining a total of 36 in vivo matured MII oocytes collected from 30 healthy women recruited for oocyte donation, found that five miRNAs such as hsa-miR-220b, miR-4262 and miR-1260a were increased in the older group (age 32 ± 2 years and high antral follicular count approx.…”

circSLC41A1 Resists Porcine Granulosa Cell Apoptosis and Follicular Atresia by Promoting SRSF1 through miR-9820-5p Sponging

“…It has been reported that miRNA is involved in SRSF1 regulation. For example, miR-505-3p targets SRSF1 to inhibit the expression of puberty-related genes, thus regulating sexual maturity [26]; also, both miR-28 and miR-505 target SRSF1 to control mouse embryonic fibroblasts (MEF) proliferation and survival [27]. Additionally, SRSF1 was reported to bind to circRNA [28] and lncRNA [29], as RNA-binding proteins (RBPs) in glioma cells and trophoblast cells, respectively, to regulate the cell proliferation process.…”