Project description:In fish, female fecundity is tightly linked to the proper completion of oogenesis that takes place in the ovary. These cellular processes have been shown to involve both endocrine and intra-ovarian factors. However, the role of small non-coding miRNAs remains largely unknown. Here, we analyzed the role of miR-202, a miRNA specifically expressed in the vertebrate gonads. We first used fluorescent in situ hybridization to determine the precise cellular expression of miR-202 in the medaka ovary. We then generated a mutant fish line (using CRISPR/Cas9 technology) to determine its role in female fecundity and oogenesis. We performed quantitative image analyses to analyze cellular modifications and a genome-wide transcriptomic approach to analyze gene expression modifications. Our results show that miR-202-5p is predominantly expressed in granulosa cells. In addition, mutant females display a drastically reduced fecundity. Our cellular and molecular analyses of ovaries from mutant females indicate that miR-202 deficiency impairs the early steps of oogenesis/folliculogenesis, which ultimately reduce female fecundity. This provides the first functional evidence that miR-202 is necessary for the female reproductive success, in particular the female fecundity, and shed new light on the regulatory mechanisms that control the early steps of follicular development.
