Elucidation of the Mechanism of Meiotic Initiation by Retinoic Acid and Neuregulin

我们利用突变小鼠和体外培养研究了神经调节蛋白（NRG）在减数分裂起始中的作用。他莫昔芬（TM）注射到Nrg1Ser - / -突变小鼠和ErbB4显性阴性转基因小鼠中，可降低精原细胞增殖和减数分裂起始。在睾丸碎片和纯化精原细胞的培养中，NRG1和RA促进精原细胞增殖和减数分裂起始。这些结果表明，当NRGs上调时，RA通过支持细胞间接诱导减数分裂，NRGs通过ErbB4受体直接诱导精原细胞减数分裂。总的来说，这些结果表明NRGs对精原细胞的增殖和减数分裂起始是必不可少的。在HeLa细胞中的研究表明，由ErbB4产生并易位到细胞核的p80与a-烯醇酶相互作用，通过损害c-myc基因转录抑制nrg1依赖性细胞增殖。

We studied the role of neuregulin (NRG) in the initiation of meiosis, using mutant mice and in vitro cultures. Tamoxifen (TM) injection into Nrg1Ser–/– mutant mice, as well as dominant-negative ErbB4 transgenic mice, decreased proliferation of spermatogonia and meiotic initiation. In cultures of testicular fragments and purified spermatogonia, NRG1 and RA promoted spermatogonial proliferation and meiotic initiation. These results indicate that in juvenile testes RA induces meiosis indirectly through Sertoli cells when NRGs are upregulated and the NRGs directly induce meiosis in spermatogonia through ErbB4 receptor. Collectively, these results indicate that NRGs are essential for the proliferation of spermatogonia and meiotic initiation.The studies in HeLa cells suggested that p80, which is generated from ErbB4 and translocates to the nuclei, interacts with a-enolase and inhibits NRG1-dependent cell proliferation by impairing the c-myc gene transcription.