Immunohistochemical distribution of proteins belonging to the receptor-mediated and the mitochondrial apoptotic pathways in human placenta during gestation

Abstract

The balance between cell death and cell proliferation and its regulation are essential features of many physiological processes and are particularly important in fetal morphogenesis and adult tissue homeostasis. Apoptosis is a type of cell suicide that is activated in two main ways: through a receptor-mediated pathway or through a mitochondrial pathway. We have investigated the immunohistochemical distribution of proteins belonging to these two pathways in human placenta during gestation by comparing their expression levels between the first and third trimester of gestation. In the first trimester, the receptor-mediated pathway prevails over the mitochondrial pathway with a moderate/intense expression of its three components, viz., Fas ligand (FasL), Fas, and caspase-8, and weak positivity of anti-apoptotic FLIP, these proteins being mainly localized in the cytotrophoblast compartment. In the third trimester of gestation, there is an increased expression of mitochondrial pathway proteins, viz., Apaf-1 and caspase-9. We have also investigated the expression level of caspase-3, the primary effector caspase of both pathways, and have observed that it is moderately expressed during gestation, being mainly localized in the cytotrophoblast during the first trimester and in both placental compartments during the third trimester of gestation. Thus, both pathways actively function in human placenta to execute cell death. By means of immunoelectron microscopy, we have further shown that, in human placenta, the two proteins of the mitochondrial pathway together with caspase-3 are localized both in the cytoplasm and in the nucleus. In particular, Apaf-1 and caspase-9 are distributed near to the nuclear envelope suggesting an important role for these two proteins in disrupting the nuclear-cytoplasmic barrier.

Cell fusion induced by ERVWE1 or measles virus causes cellular senescence

“…One possibility is that mechanisms induced in senescent cells help to maintain viability of the syncytium during pregnancy. Senescent cells are known to be resistant to apoptosis, and this resistance might support syncytiotrophoblast viability during pregnancy despite activation of caspase-8 in the cytotrophoblast in the initial stages of syncytiotrophoblast formation (De Falco et al 2004). Activated caspase-8 can lead to apoptosis in other tissues (Varfolomeev et al 1998) but becomes inactivated in the syncytiotrophoblast (De Falco et al 2004).…”

“…Senescent cells are known to be resistant to apoptosis, and this resistance might support syncytiotrophoblast viability during pregnancy despite activation of caspase-8 in the cytotrophoblast in the initial stages of syncytiotrophoblast formation (De Falco et al 2004). Activated caspase-8 can lead to apoptosis in other tissues (Varfolomeev et al 1998) but becomes inactivated in the syncytiotrophoblast (De Falco et al 2004). A senescent phenotype of the syncytiotrophoblast, including high DCR2 expression, might contribute to this inactivation and thus support the viability of these cells.…”

Kidney‐Replenishing Herb Induces SOCS‐3 Expression via ERK/MAPK Pathway and Improves Growth of the First‐Trimester Human Trophoblast Cells

“…The placenta supply nutrition to the growing fetus, of which development is vital for fetal survival and growth [15]. Placental function is essential for the development of the mammalian embryo during pregnancy [16]. Maintenance placental normal function depends on the perfect balance among trophoblast layer proliferation, maturation, and apoptosis [17].…”

Modulation of Wolframin Expression in Human Placenta during Pregnancy: Comparison among Physiological and Pathological States

“…Kim et al [42] and De Falco et al [19, 24] have demonstrated that the expression of the antiapoptotic factor, Bcl-2, diminishes as gestation progresses, suggesting that a parturition-associated biological change might induce apoptosis in the placental villi [31]. Recently, we have compared the expression of the proapoptotic Bax protein between first trimester VTGs and first trimester LPs, showing a strong increase of Bax expression in the latter compared to the low/moderate Bax immunopositivity in the former, thereby suggesting that upregulation of apoptosis may be involved in pregnancy complications leading to miscarriage.…”

“…Apoptosis plays an important role in formation of human placenta [19–21]. Several investigators have demonstrated that the apoptotic rate increases progressively during normal gestation, which has been interpreted as part of normal placental development [22–25].…”