Division of Molecular Genetics and Development, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Biol Reprod. 2010 Dec;83(6):1005-14. doi: 10.1095/biolreprod.110.086801. Epub 2010 Aug 25.
Germ cell sex differentiation in the mouse embryo is denoted by meiosis entry in females and mitotic arrest in males. Because p38 mitogen-activated protein kinase (MAPK) signaling initiates mitotic arrest in other differentiating cell types, we investigated its potential role in XY germ cell differentiation in mice. We report that p38 MAPK is phosphorylated and therefore activated only in XY germ cells around the time of sex differentiation. Quantitative RT-PCR analysis showed that 14 known targets of p38 MAPK signaling are expressed in the embryonic gonads at this time and that five of these targets (Mapkapk5, Max, Myc, Hbp1, and Cebpa) have expression profiles similar to that of activated p38 MAPK. Inhibition of p38 MAPK signaling in XY germ cells ex vivo reduced expression of the pluripotency marker POU5F1 and increased the expression of Stra8 and SYCP3, premeiosis and meiosis markers, respectively, to levels approaching those observed in XX germ cells. These data suggest that p38 MAPK signaling antagonizes entry into meiosis in XY germ cells, instead directing them toward mitotic quiescence and a spermatogenic fate.
在雌性小鼠胚胎中，生殖细胞的性别分化表现为减数分裂的启动，而在雄性中则表现为有丝分裂的停滞。由于 p38 丝裂原活化蛋白激酶（MAPK）信号通路在其他分化细胞类型中启动有丝分裂的停滞，因此我们研究了其在雄性小鼠生殖细胞分化中的潜在作用。我们发现，p38 MAPK 仅在性分化时的 XY 生殖细胞中发生磷酸化和激活。定量 RT-PCR 分析表明，14 种已知的 p38 MAPK 信号通路靶基因在此时表达于胚胎性腺中，其中 5 种靶基因（Mapkapk5、Max、Myc、Hbp1 和 Cebpa）的表达模式与激活的 p38 MAPK 相似。体外抑制 XY 生殖细胞中的 p38 MAPK 信号通路，降低了多能性标记物 POU5F1 的表达，同时增加了 Stra8 和 SYCP3 的表达，分别达到接近 XX 生殖细胞中观察到的减数分裂和有丝分裂标记物的水平。这些数据表明，p38 MAPK 信号通路拮抗了 XY 生殖细胞进入减数分裂，而是促使它们进入有丝分裂静止状态，并向精子发生方向分化。
