Bcl-2 and Bax regulation of apoptosis in germ cells during prenatal oogenesis in the mouse embryo
Bcl-2 and Bax regulation of apoptosis in germ cells during prenatal oogenesis in the mouse embryo
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DOI：
10.1038/sj.cdd.4400561
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发表时间：
1999-09-01
影响因子：
12.4
通讯作者：
Piacentini, M
中科院分区：
文献类型：
--
作者：
De Felici, M;Di Carlo, A;Piacentini, M
细胞凋亡是胚胎卵巢发育过程中原始生殖细胞和卵母细胞变性的主要原因。在这项研究中，我们研究了免疫组织化学和免疫印迹的表达的抗和促凋亡蛋白Bcl-2和Bax的原始生殖细胞和胎儿卵母细胞在纳塔尔前卵子发生在小鼠胚胎。虽然Bcl-2和Bax在体内原始生殖细胞中检测不到，但这两种蛋白质在培养中发生凋亡时均上调。治疗与干细胞因子（SCF），生长因子已知部分减少原始生殖细胞凋亡，导致Bax的表达减少。Bcl-2在进入减数分裂的卵母细胞中几乎检测不到，并且在减数分裂前期I检测阶段其表达没有变化。与此相反，高水平的Bax蛋白表达在退化的卵母细胞中，而低水平的蛋白存在于许多明显健康的卵母细胞中，在15.5天后，coconflation（d.p.c.）和出生时，当Bax下调时，从cocopletion后15.5天（d.p.c.）在体外，卵巢通过前期I进展并在粗线期/双线期阶段经历凋亡波，显示出与体内条件相似的Bax表达模式。尽管SCF在培养液中的加入显著降低了粗线期/双线期卵母细胞的凋亡，但不可能将这种效应与存活卵母细胞中Bax的下调直接相关。这些结果表明，而Bcl-2和Bax之间的平衡可能调节细胞凋亡的增殖下的原始生殖细胞的SCF的部分控制。减数分裂卵母细胞中的细胞凋亡可能是由于内在的减数分裂检查点，其作用是监测异常的DNA重组，而不是生长因子依赖的过程。多余卵母细胞的消除可能是由卵巢内SCF等生长因子的可用性控制的后续凋亡现象。
Apoptosis is the main cause of primordial germ cell and oocyte degeneration in the developing fetal ovary. In this study we examined by immunohistochemistry and immunoblotting the expression of the anti- and pro-apoptotic proteins Bcl-2 and Bax in primordial germ cells and fetal oocytes during pre natal oogenesis in the mouse embryo. While Bcl-2 and Bax were not detectable in primordial germ cells in vivo, both proteins were upregulated when they undergo apoptosis in culture. Treatment with the stem cell factor (SCF), a growth factor known to partially reduce primordial germ cell apoptosis, resulted in decreased Bax expression. Bcl-2 was barely detectable in oocytes entering into meiosis and its expression did not change during the stage of meiotic prophase I examined. On the contrary, high levels of Bax was expressed in degenerating oocytes while low levels of the protein was present in many apparently healthy oocytes between 15.5 days post coitum (d.p.c.) and birth, when Bax was down-regulated, Oocytes isolated from 15.5 days post coitum (d.p.c.) ovaries that progress through prophase I and undergo a wave of apoptosis at the stage of pachytene/diplotene in vitro, showed a pattern of Bax expression similar to the in vivo condition. Although the addition of SCF to the culture medium reduced significantly apoptosis in oocytes at the pachytene/diplotene stages, it was not possible to directly correlate this eff ect with the downregulation of Bax in the surviving oocytes. These findings indicate that whereas a balance between Bcl-2 and Bax might regulate apoptosis of proliferating primordial germ cells under a partial control by SCF. Bax-mediated apoptosis in meiotic oocytes may be due to intrinsic meiotic checkpoints which act to monitor aberrant DNA recombination rather than to a growth factor dependent process. Elimination of supernumerary oocytes might be a subsequent apoptotic phenomenon controlled by the availability of growth factors such as SCF within the ovary.