Increased apoptosis of trophoblasts from pregnancies complicated by intrauterine growth restriction is associated with aberrant Fas-associated death domain (FADD) expression

Abstract

Intrauterine growth restriction (IUGR) is one of the most common pregnancy complications worldwide. However, the pathogenesis of IUGR is not completely clear. The authors conducted this study to investigate trophoblast apoptosis and the underlying molecular mechanisms in fetal membranes from pregnancies complicated by IUGR, in order to further understand the potential pathological processes involved in human IUGR. Fetal membranes were obtained from patients with pregnancies affected by IUGR (n = 10) and normal term pregnancies (n = 10). Nine of the ten delivered infants had a birth weight below the 10th percentile for gestational age, accompanied by morphological differences, and other extensive lesions common in IUGR cases. The fetal membranes were subjected to enzymatic digestion and flow cytometric analysis to evaluate apoptosis, as well as determination of cleaved caspase-3 and poly (ADPribose) polymerase (PARP) products. Expression of Fas-associated death domain (FADD) protein was detected using Western blot. Increased apoptosis was observed in the trophoblasts of fetal membranes from IUGR cases compared with normal control pregnancies. Trophoblasts from the fetal membranes of IUGR pregnancies exhibited consistently increased expression of the FADD protein compared to those from the normal pregnancies. The present results revealed significantly enhanced apoptosis and aberrant FADD expression in the trophoblasts from fetal membranes obtained from pregnancies complicated by IUGR compared with normal pregnancies. The disrupted balance of trophoblast apoptosis may be associated with aberrant FADD expression, which contributes to the pathological processes associated with IUGR.