Effects of retinoids on the meiosis in the fetal rat ovary in culture

We investigated the effect of retinoids on the entrance of female germ cells into meiotic prophase and their progression through it, using explants of rat ovaries from 14.5 days post coı̈tum (dpc) fetuses cultured with or without 10 −6 M retinoic acid (RA) or 10 −9 M retinoic acid receptor α (RARα) specific agonist. The percentages of oogonia and of oocytes at each meiotic stage in the ovary were evaluated at explantation (D0) and after 3 (D3), 5 (D5) and 9 (D9) days of culture and on equivalent stages in vivo (i.e. 17.5 and 23.5 dpc). The number of germ cells per ovary were counted at D0, D3 and D9. Newly explanted (D0) ovaries contained no germ cell in meiosis. In control medium some germ cells had spontaneously reached the stage leptotene and very few the zygotene on D3. The first pachytene were observed on D5 and the first diplotene on D9. This pattern mimicked that which occurs in vivo although with a slight delay. RA reduced the percentage of oogonia by more than half and increased the percentage of zygotene by more than 22-fold on D3, showing that it accelerated entrance into meiosis. This effect was also observed in response to RARα agonist. RA increased the percentage of zygotene and reduced the percentage of pachytene on D9, showing that it can also delay the zygotene/pachytene transition. Lastly, RA reduced the total number of germ cells present on D3 but not on D9. This may be the result of a double effect of RA on the number of germ cells: negative when the cells are in proliferation (D0 to D3) and positive when they entered in meiotic prophase (after D3). Thus, RA is a potential regulator of germ cells meiosis and number in the fetal ovary.