The microARN-202 (miR-202) controls female fecundity by regulating oogenesis in medaka. The microARN-202 (miR-202) controls female fecundity by regulating oogenesis in medaka

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. Overall design: Expression profiling of ovary from wild-type female and miR202 knock-out female