Boumela I, Guillemin Y, Guérin J-F, Aouacheria A
CNRS UMR 5086, IFR 128, institut de biologie et chimie des protéines, université de Lyon-1, 69367 Lyon, France.
Gynecol Obstet Fertil. 2009 Sep;37(9):720-32. doi: 10.1016/j.gyobfe.2009.06.004. Epub 2009 Aug 13.
Apoptosis, a form of cell death by self-destruction, has been reported in gametes and preimplantation embryos both in vitro and in vivo. Recent evidence suggests that cell death processes, whose control deserves to be elucidated, can impact embryo developmental competence. Moreover, quality of the gametes (particularly of the oocytes) is relevant not only for their survival rates but exert an influence during the early stages of embryo development. Thus, the investigation of apoptosis-related genes and mechanisms in early embryos is crucial. BCL-2 family proteins, through balanced interactions between pro- and anti-death members, play a pivotal role in controlling cell life and death. In this article, we review the literature concerning the expression of Bcl-2 family members in gametes and early embryos. Research results indicate that the various Bcl-2 subfamilies (pro- and anti-apoptotic "multidomain" family members and "BH3-only" death factors) exhibit a dynamic expression pattern during male and female gamete differentiation and early embryo development. While pro-apoptotic Bax protein plays a critical role in germ cell and early embryo degeneration, the relative importance of the prosurvival (Bcl-2, Bcl-xL, Bcl-w, Mcl-1) and "BH3-only" (Bim, Bad, Bik) members is not clear. Although information on expression patterns of Bcl-2 family transcripts and proteins is necessary, other elements such as transcriptional control (by environmental stimuli), subcellular localization and post-translational modifications should also be taken into account. Aside from basic research, a better understanding of apoptosis-related proteins and mechanisms involved in gamete and embryo viability at the molecular level may provide new guides for diagnosis and therapeutic strategies.
细胞凋亡是一种自我毁灭的细胞死亡形式,已在体外和体内的配子及植入前胚胎中被报道。最近的证据表明,细胞死亡过程(其控制机制尚待阐明)会影响胚胎的发育能力。此外,配子(尤其是卵母细胞)的质量不仅与其存活率相关,还会在胚胎发育的早期阶段产生影响。因此,研究早期胚胎中与细胞凋亡相关的基因和机制至关重要。BCL-2家族蛋白通过促死亡成员和抗死亡成员之间的平衡相互作用,在控制细胞生死中起关键作用。在本文中,我们回顾了有关Bcl-2家族成员在配子和早期胚胎中表达的文献。研究结果表明,各种Bcl-2亚家族(促凋亡和抗凋亡的“多结构域”家族成员以及“仅含BH3结构域”的死亡因子)在雌雄配子分化和早期胚胎发育过程中呈现出动态表达模式。虽然促凋亡的Bax蛋白在生殖细胞和早期胚胎退化中起关键作用,但促存活成员(Bcl-2、Bcl-xL、Bcl-w、Mcl-1)和“仅含BH3结构域”成员(Bim、Bad、Bik)的相对重要性尚不清楚。尽管关于Bcl-2家族转录本和蛋白表达模式的信息是必要的,但其他因素,如转录调控(受环境刺激)、亚细胞定位和翻译后修饰也应予以考虑。除了基础研究外,在分子水平上更好地理解与配子和胚胎活力相关的凋亡相关蛋白和机制,可能为诊断和治疗策略提供新的指导。