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Publication : Sex-specific timing of meiotic initiation is regulated by Cyp26b1 independent of retinoic acid signalling.

First Author  Kumar S Year  2011
Journal  Nat Commun Volume  2
Pages  151 PubMed ID  21224842
Mgi Jnum  J:222363 Mgi Id  MGI:5644404
Doi  10.1038/ncomms1136 Citation  Kumar S, et al. (2011) Sex-specific timing of meiotic initiation is regulated by Cyp26b1 independent of retinoic acid signalling. Nat Commun 2:151
abstractText  Sex-specific initiation of meiosis in the fetal ovary has been suggested to require retinoic acid (RA) for induction of Stra8, with expression of the RA-degrading enzyme Cyp26b1 in fetal testis delaying meiosis until postnatal development. In this study, we investigate Raldh2(-/-) mice lacking RA synthesis and signalling in mesonephros and adjacent gonad and reveal that Stra8 expression in the fetal ovary does not require RA signalling. In contrast to previous observations, we find that Stra8 is expressed in the absence of physiologically detectable levels of RA. Ketoconazole inhibition of Cyp26b1 in Raldh2(-/-) testis allows RA-independent induction of Stra8, but only when the mesonephros remains attached, pointing to a non-RA signal from the mesonephros that induces Stra8 in the adjacent gonad. These findings demonstrate that Cyp26b1 prevents the onset of meiosis by metabolizing a substrate other than RA that controls Stra8 expression, thus changing the paradigm for how studies on Cyp26 function are conducted.
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