Molecular Biology of Mammalian Germ Cells

根据y染色体的存在，双电位哺乳动物性腺变成睾丸或卵巢，性别特异性基因确保适当的性腺生成和性发育。采用二维凝胶电泳和质谱法比较正常新生儿卵巢和FIGLA无效新生儿卵巢的蛋白表达谱。在FIGLA阴性新生儿卵巢中检测到睾丸特异性蛋白，表明男性性别特异性遗传途径受到抑制。为了进一步验证这一假说，我们在人类精原细胞特异性启动子（hTSPY）的作用下，建立了在雄性生殖细胞中异位表达FIGLA的转基因小鼠系。虽然最初是可生育的，但转基因雄性小鼠的生殖力和睾丸大小下降了正常小鼠的73%。在正常小鼠中观察到的7个雄性生殖细胞特异性基因的表达在成熟的转基因睾丸中转录下调。虽然精子发生的所有阶段最初都被检测到，但在精管中偶见液泡，与生殖细胞凋亡斑块一致。随着转基因雄性小鼠年龄的增长，生殖细胞系进一步逐渐枯竭，同时空泡化和凋亡增加。性腺组织病理学的严重程度与生育能力下降相关，在5个月后，精子数量急剧减少，运动能力差，转基因精子在体外与正常卵子结合和受精的能力被破坏。总的来说，这些数据强调FIGLA既是卵母细胞特异性的激活因子，也是雌性性腺成功发育所必需的睾丸特异性基因的抑制因子。

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.