Straszewski-Chavez Shawn L, Abrahams Vikki M, Mor Gil
Department of Obstetrics, Gynecology and Reproductive Sciences, Reproductive Immunology Unit, Yale University School of Medicine, 333 Cedar Street FMB 301, New Haven, CT 06520, USA.
Endocr Rev. 2005 Dec;26(7):877-97. doi: 10.1210/er.2005-0003. Epub 2005 May 18.
Apoptosis is important for normal placental development, but it may also be involved in the pathophysiology of pregnancy-related diseases. Normal placental development is dependent upon the differentiation and invasion of the trophoblast, the main cellular component of the placenta. Trophoblast apoptosis increases in normal placentas as gestation proceeds, and a greater incidence of trophoblast apoptosis has been observed in pregnancies complicated by preeclampsia or intrauterine growth retardation (IUGR). In response to different stimuli, apoptosis may be initiated extrinsically by the death receptor pathway or intrinsically by the mitochondrial pathway. The central executioners of apoptosis are the caspases, which cleave numerous vital cellular proteins to affect the apoptotic cascade. By inhibiting caspase activation, several endogenous inhibitors, including flice-like inhibitory proteins (FLIPs), inhibitors of apoptosis (IAPs), and antiapoptotic Bcl-2 family members, can prevent further propagation of the death signal. Macrophages present at the maternal-fetal interface may also contribute to trophoblast survival by removing apoptotic cells and producing cytokines and growth factors, which influence the progression of the apoptotic cascade. This review focuses on the role of apoptosis in trophoblast development and differentiation, the molecular mechanisms by which normal trophoblast apoptosis can occur, and how it is regulated to prevent excessive trophoblast apoptosis and possible pregnancy complications.
细胞凋亡对胎盘正常发育很重要，但它也可能参与妊娠相关疾病的病理生理过程。正常胎盘发育依赖于胎盘主要细胞成分——滋养层细胞的分化和侵袭。随着妊娠进展，正常胎盘的滋养层细胞凋亡增加，并且在子痫前期或胎儿生长受限（IUGR）的妊娠中观察到滋养层细胞凋亡发生率更高。针对不同刺激，细胞凋亡可通过死亡受体途径从外部启动，或通过线粒体途径从内部启动。细胞凋亡的核心执行者是半胱天冬酶，它们切割众多重要的细胞蛋白以影响凋亡级联反应。通过抑制半胱天冬酶激活，包括类Fas相关死亡结构域蛋白样抑制蛋白（FLIPs）、凋亡抑制蛋白（IAPs）和抗凋亡Bcl-2家族成员在内的几种内源性抑制剂可阻止死亡信号的进一步传播。存在于母胎界面的巨噬细胞也可能通过清除凋亡细胞并产生影响凋亡级联反应进程的细胞因子和生长因子来促进滋养层细胞存活。本综述重点关注细胞凋亡在滋养层细胞发育和分化中的作用、正常滋养层细胞凋亡发生的分子机制，以及如何对其进行调节以防止滋养层细胞过度凋亡和可能出现的妊娠并发症。
