Involvement of retinoic acid (ATRA) signaling and DMRT1 in rabbit male and female germ cell fates
Implication de la signalisation de l'acide rétinoïque (ATRA) et de DMRT1 dans le devenir des cellules germinales mâles et femelles chez le lapin
Résumé
Retinoic acid (RA), a metabolite of vitamin A, is a significant player in cell differentiation from the primary stages of vertebrate embryo development to the adult, where it plays roles in many physiological mechanisms. Our lab generated a transgenic rabbit model expressing a recombinant RA-sensitive transcriptional gene, including the green fluorescent protein (GFP) reporter gene. Thanks to this model, we could define that some organs of rabbit fetuses began to be sensitive to RA from 11 days post-coitum (dpc) in both sexes. Ten days later, when organogenesis is well established, GFP is expressed in various organs known to be RA-sensitive, like the heart, lungs, eyes or kidneys. In female, we found that retinoic acid signaling starts at 24 dpc in germ cells about ten days before they enter into meiosis a few days after birth. Since DMRT1 may be related to the meiotic process due to its involvement in Stra8 up-regulation in mice, we were investigated the potential link between RA sensitivity and DMRT1 in rabbit germ cells. Firstly, using our DMRT1 mutant rabbit line, we highlighted the DMRT1 involvement in testis determination and ovary meiotic initiation. However, we also observed azoospermia that appeared with aging in the XY DMRT1+/- rabbits. At 3 days post-partum (dpp), we noted that heterozygous XY rabbits for DMRT1 have a delay (i) in germ cell differentiation with the maintenance of pluripotency and (ii) in RA sensitivity.
Thus, with these two rabbit model lines, we can follow the sensitivity of retinoic acid in rabbit germ cells upon disrupted DMRT1 expression. This characterization is underway at the time of male puberty and at foetal stages in female, during germ cells proliferation and ovigerous nests formation.
Origine : Fichiers produits par l'(les) auteur(s)