The Role of Apoptosis in the Regulation of Trophoblast Survival and Differentiation during Pregnancy

Abstract

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.

XAF1 Mediates Tumor Necrosis Factor-α-induced Apoptosis and X-linked Inhibitor of Apoptosis Cleavage by Acting through the Mitochondrial Pathway

“…XIAP and several other IAP family members have been shown to be expressed by the trophoblast throughout normal pregnancy (3, 38 -40) and are thought to play a critical role in regulating trophoblast cell survival (41). The function of the IAP family is inhibited by a group of proteins that includes Smac/DIABLO, OMI/HtrA2, and XAF1, albeit by different mechanisms (9, 19 -23).…”

Apoptose e maturação placentária bovina: um estudo imunohistoquímico e morfométrico

“…A maturação placentária é mediada pela apoptose das células das criptas do epitélio materno e ocorre durante toda a gestação na renovação normal (Boos et al 2003), aumentando no terço final. Straszewski-Chavez et al (2005) avaliaram placentas humanas e demonstraram maior apoptose nos sítios de invasão do trofoblasto no epitélio materno, sugerindo que este processo facilite a invasão do trofoblasto e a remodelação dos vilos endometriais.…”

“…Liu et al (2003) relataram aumento da marcação para caspase-3 no sincicio e citotrofoblasto ao decorrer da gestação. Padrões crescentes de apoptose na placenta humana durante a gestação também foi observada e relacionada à constante renovação e remodelação tecidual como um processo natural por Straszewski-Chavez et al (2005).…”

“…Isto explica a morfologia característica das células apoptóticas como condensação nuclear, bolhas na membrana e retração celular. A deoxyribonuclease ativada pela caspase cliva o DNA inespecificamente em fragmentos de aproximadamente 200 pares de bases matando as célu-las (Straszewski-Chavez et al 2005). O aumento do índice apoptótico em placentomas com o avanço da idade gestacional em vacas foi comprovado morfologicamente com a reação de Tunel por Meça et al (2011).…”

Maternal endotoxin-induced fetal growth restriction in rats: Fetal responses in toll-like receptor

“…Apoptosis and the factors involved in the regulation are associated with almost all stages of development and trophoblast differentiation. 8 One of the factors that can lead to the increased apoptosis of trophoblast during pregnancy is intrauterine infection. 9 The exact mechanism of infection resulted the progression of this disorder is not clearly understood, but recent studies suggested that bacterial products have a direct effect on the trophoblast.…”