Cystic proliferation of embryonic germ stem cells is necessary to reproductive success and normal mating behavior in medaka

The production of an adequate number of gametes in both sexes is necessary for normal reproduction, for which the regulation of proliferation from early gonadal development to adulthood is key. Cystic proliferation of embryonic stem germ cells prior the onset of gametogenesis is an especially important step prior to the beginning of meiosis. However, in vertebrates, the molecular regulators of cystic proliferation remain unknown. Here, we report that ndrg1b, a member of the N-myc downstream regulated family, is an important regulator of cystic proliferation in medaka. We generated mutants of ndrg1b that led to a disruption of proliferation type II, independently of the TGF-{beta} signaling pathway. This loss of cystic proliferation was observed from embryogenic to adult stages, impacting the success of gamete production and reproductive parameters such as spawning and fertilization. Interestingly, the depletion of cystic proliferation of the ndrg1b mutant also impacted male sexual behavior, with a decrease of mating vigor. These data illustrate why it is also necessary to consider gamete production capacity in order to analyze reproductive behavior. HIGHLIGHTSO_LINdrg1b is involved in the regulation of cystic proliferation in gonad from embryo to adulthood. C_LIO_LIThe cystic proliferation is independently of the TGF-{beta} signaling pathway. C_LIO_LIDecrease of production of gametes declines reproductive success for both sexes. C_LIO_LIReduction of cystic proliferation declines male sexual behavior, with a decrease of mating vigor. C_LI