Sex-specific timing of meiotic initiation is regulated by Cyp26b1 independent of retinoic acid signalling.
Sex-specific timing of meiotic initiation is regulated by Cyp26b1 independent of retinoic acid signalling.
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DOI：
10.1038/ncomms1136
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发表时间：
2011-01-11
影响因子：
16.6
通讯作者：
Duester, Gregg
中科院分区：
文献类型：
--
作者：
Kumar, Sandeep;Chatzi, Christina;Brade, Thomas;Cunningham, Thomas J.;Zhao, Xianling;Duester, Gregg
胎儿卵巢减数分裂的性别特异性启动被认为需要维甲酸（RA）诱导Stra 8，RA降解酶Cyp 26 b1在胎儿睾丸中的表达延迟减数分裂，直到出生后的发展。在这项研究中，我们研究了在中肾和邻近性腺中缺乏RA合成和信号传导的Raldh 2 −/−小鼠，并揭示了胎儿卵巢中的Stra 8表达不需要RA信号传导。与以前的观察结果相反，我们发现Stra 8是在没有生理检测水平的RA的情况下表达的。酮康唑抑制Raldh 2 −/−睾丸中Cyp 26 b1可以不依赖RA诱导Stra 8，但仅当中肾保持附着时，这表明来自中肾的非RA信号在相邻性腺中诱导Stra 8。这些研究结果表明，Cyp 26 b1通过代谢RA以外的控制Stra 8表达的底物来阻止减数分裂的发生，从而改变了Cyp 26功能研究的范式。
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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