Abstract
In vertebrates, one of the first recognizable sex differences in embryos is the onset of meiosis, known to be regulated by retinoic acid (RA) in mammals. We investigated in medaka a possible meiotic function of RA during the embryonic sex determination (SD) period and in mature gonads. We found RA mediated transcriptional activation in germ cells of both sexes much earlier than the SD stage, however, no such activity during the critical stages of SD. In adults, expression of the RA metabolizing enzymes indicates sexually dimorphic RA levels. In testis, RA acts directly in Sertoli, Leydig and pre-meiotic germ cells. In ovaries, RA transcriptional activity is highest in meiotic oocytes. Our results show that RA plays an important role in meiosis induction and gametogenesis in adult medaka but contrary to common expectations, not for initiating the first meiosis in female germ cells at the SD stage.
Highlights
In vertebrates, the decision as to whether the bipotential gonad anlage will become testis or ovary is a critical stage in embryonic development
Studying the timing of production of retinoic acid (RA) and its activity in the germ cells during development and in the adult gonad of medaka, we show that RA has an important role in meiosis at later stages of gonad development rather than in initial sex determination in the embryo
Our findings allow us to suggest a complementary hypothesis for the control of meiosis entry through RA, adding to what was proposed for zebrafish in the adult gonad
Summary
The decision as to whether the bipotential gonad anlage will become testis or ovary is a critical stage in embryonic development This complex sex determination process includes fate determination and cell differentiation within two fundamentally different programs, the female and the male. More recent data comparing fish and mammals indicated discrepancies in the gene expression patterns and in the interactions of the downstream gonadal regulatory network, which mighty reflect a plasticity of this regulatory network to various degrees during vertebrate evolution[2] In this respect, the development of the gonad is different from all other major vertebrate organs, where generally a high conservation of molecular mechanisms from fish up to humans has been noted[3]. This information together with the fact that no sequence of stra[8] was found far in most teleost genomes including medaka, poses the question whether RA has a similar role in meiosis and gonadogenesis in fish as in mammals[23]
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