Molecular Biology of Mammalian Germ Cells

根据Y染色体的存在，双潜能哺乳动物的性腺变成睾丸或卵巢，性别特有的基因确保适当的性腺发生和性发育。应用双向凝胶电泳法和质谱仪，比较正常新生儿卵巢和正常新生儿卵巢的蛋白质表达谱。在无花果新生儿卵巢中检测到的睾丸特异蛋白表明，男性特有的遗传途径受到了抑制。为了进一步研究这一假说，我们建立了在人精原特异性启动子(HTSPY)启动子作用下，在雄性生殖细胞中异位表达Figla的转基因小鼠系。尽管转基因雄性小鼠最初是有生育能力的，但它们的生育力和睾丸大小都下降了73%。在正常小鼠中观察到的七个雄性生殖细胞特异性基因在成熟的转基因睾丸中转录下调。虽然最初检测到了精子发生的所有阶段，但在生精小管中零星地观察到空泡，这与生殖细胞凋亡的斑块一致。随着转基因雄性小鼠年龄的增长，生殖细胞谱系的进一步枯竭伴随着空泡化和细胞凋亡的增加。性腺组织病理学的这种不断升级的严重性与生育力的下降有关，这种下降在5个月后就完成了，当时精子数量的急剧减少和运动能力的下降消除了转基因精子在体外结合正常卵子并使其受精的能力。总而言之，这些数据突出了作为卵母细胞特异性激活剂和睾丸特异性基因抑制因子对女性性腺成功发育所必需的作用。

Depending on the presence of a Y-chromosome, the bipotential mammalian gonad becomes a testis or an ovary and gender-specific genes ensure appropriate gonadogenesis and sex development. Using two-dimensional gel electrophoresis and mass spectrometry, protein expression profiles of newborn normal and FIGLA null newborn ovaries were compared. The detection of testis-specific proteins in FIGLA null newborn ovaries suggested repression of male sex-specific genetic pathways. To further investigate this hypothesis, transgenic mouse lines ectopically expressing FIGLA in male germ cells under a human spermatogonial-specific (hTSPY) promoter were established. Although initially fertile, transgenic male mice had decreased fecundity and testicular size 73% of normal. The expression of seven male germ cell-specific genes observed in normal mice was transcriptionally down-regulated in mature transgenic testes. Although all stages of spermatogenesis were initially detected, vacuoles were sporadically observed within seminiferous tubules consistent with patches of germ cell apoptosis. As transgenic male mice aged, there was further progressive depletion of germ cell lineages coupled with a increased vacuolization and apoptosis. This escalating severity of gonadal histopathology correlated with decreased fertility that was complete by 5 months when dramatic reductions in sperm counts and poor motility abolished the ability of transgenic sperm to bind and fertilized normal eggs in vitro. Collectively, these data high-light FIGLA both as an activator oocyte-specific and as a repressor of testis-specific genes necessary for successful development of the female gonad.