DMRT1 promotes oogenesis by transcriptional activation of Stra8 in the mammalian fetal ovary.
DMRT1 promotes oogenesis by transcriptional activation of Stra8 in the mammalian fetal ovary.
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DOI：
10.1016/j.ydbio.2011.05.658
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发表时间：
2011-08-01
影响因子：
2.7
通讯作者：
Zarkower D
中科院分区：
文献类型：
--
作者：
Krentz AD;Murphy MW;Sarver AL;Griswold MD;Bardwell VJ;Zarkower D
Dmrt 1属于保守的性调节基因DM结构域基因家族。在小鼠中，Dmrt 1在两性的生殖嵴（性腺原基）中表达，然后在性别决定后不久成为睾丸特异性的。DMRT 1在睾丸分化中的重要作用已得到充分证实，包括减数分裂诱导物Stra8的转录抑制。然而，Dmrt 1突变的女性是可育的，Dmrt 1在卵巢中的作用尚未研究。在这里，我们发现在小鼠胚胎卵巢中的大多数Dmrt 1突变生殖细胞中，STRA8的表达大大降低，并且在减数分裂前期不能正确定位SYCP 3和γH2AX。胎儿卵巢中缺乏DMRT 1导致幼年卵巢中形成更少的原始卵泡，尽管这些卵泡足以生育。全基因组染色质免疫组化（ChIP芯片）和定量ChIP（qChIP）结合mRNA表达谱表明，在胎儿生殖细胞中Stra8的转录激活是DMRT 1在女性中的主要功能，并且这种调节可能是直接的。因此，DMRT1控制Stra8的性别特异性，在胎儿卵巢中激活它，在成年睾丸中抑制它。
Dmrt1 belongs to the DM domain gene family of conserved sexual regulators. In the mouse Dmrt1 is expressed in the genital ridge (the gonadal primordium) in both sexes and then becomes testis-specific shortly after sex determination. The essential role of DMRT1 in testicular differentiation is well established, and includes transcriptional repression of the meiotic inducer Stra8. However Dmrt1 mutant females are fertile and the role of Dmrt1 in the ovary has not been studied. Here we show in the mouse that most Dmrt1 mutant germ cells in the fetal ovary have greatly reduced expression of STRA8, and fail to properly localize SYCP3 and γH2AX during meiotic prophase. Lack of DMRT1 in the fetal ovary results in the formation of many fewer primordial follicles in the juvenile ovary, although these are sufficient for fertility. Genome-wide chromatin immunoprecipitiation (ChIP-chip) and quantitative ChIP (qChIP) combined with mRNA expression profiling suggests that transcriptional activation of Stra8 in fetal germ cells is the main function of DMRT1 in females, and that this regulation likely is direct. Thus DMRT1 controls Stra8 sex-specifically, activating it in the fetal ovary and repressing it in the adult testis.
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