Changes in Proliferative Potential, Apoptosis and Bcl-2 Protein Expression in Cytotrophoblasts and Syncytiotrophoblast in Human Placenta over the Course of Pregnancy.

Abstract

Abstract.In order to evaluate placental trophoblast proliferation and apoptosis during pregnancy, we investigated proliferating cell nuclear antigen (PCNA) expression, apoptosis and Bcl-2 protein expression in the human placenta using avidin/biotin immunoperoxidase method to examine PCNA and Bcl-2 protein expression, and TUNEL method to assess apoptosis. The appearance of apoptotic cells in very early term placental trophoblasts was also examined by transmission electron microscopy.PCNA was immunolocalized in the nuclei of cytotrophoblasts (C-cells). Determination of the mean percentage of PCNA-positive nuclei of C-cells revealed that PCNA expression in C-cells was highest in very early term (4th to 5th wk) placentas and significantly decreased with the advance of pregnancy. Bcl-2 protein was immunolocalized in the cytoplasm of syncytiotrophoblast (S-cell), being least abundant in very early term placentas, less abundant in early term and midterm placentas, and most abundant in term placentas.On the basis of TUNEL method, apoptosis was apparent in the nuclei of both C-cells and S-cell. The apoptosis positive rate of C-cell nuclei was highest in very early term 4th to 5th wk placentas, and significantly decreased in early term 7th to 9th wk and midterm placentas, but somewhat increased in term placentas compared to that in midterm placentas. On the other hand, apoptosis positive rate of S-cell nuclei was remarkably higher only in very early term 4th to 5th wk placentas compared to that in early term, midterm and term placentas.Transmission electron microscopy revealed the appearance of apoptotic nucleus in very early term placental trophoblasts.These results demonstrate for the first time that apoptosis in the human normal placenta predominates in both C-cells and S-cell in very early term 4th to 5th wk pregnancy and drastically diminished after 7th wk of pregnancy.An apparent increase in apoptosis in C-cells in term placentas compared to that in midterm placentas may reflect aging of the placenta or parturitionassociated biological change. The abundant expression of Bcl-2 protein in S-cell in term placentas may be responsible for the diminished occurrence of apoptosis in S-cell in term placentas.

HSV-2 enhances ZIKV infection of the placenta and induces apoptosis in first-trimester trophoblast cells

“…First-trimester trophoblast cells are highly proliferative while third trimester trophoblast cells are not. 32 Infection with ZIKV was further confirmed by transmission electron microscopy, which showed the presence of ZIKV within the cells (Fig. 1C).…”

Birth and death: Evidence for the same biologic clock

“…The majority of the apoptotic cells were found in the trophoblast layer; and no significant differences were observed between placentas obtained after vaginal delivery compared to Cesarean section-suggesting that apoptosis was not caused by vaginal delivery. 50 Ishihara et al 51 also used TUNEL assays to demonstrate that apoptosis in the syncytiotrophoblast cells remained low at term, whereas, for the cytotrophoblast cells, apoptosis reached its nadir during the second trimester and then increased threefold to fourfold at term. 51 Magee et al 52 confirmed significant levels of TUNEL-positive cells and proapoptotic proteins (including Fas, FasL, caspase, and PARP) in term human placentas; interestingly, the apoptosis markers were significantly decreased in placentas from pregnancies complicated by gestational diabetes.…”

“…50 Ishihara et al 51 also used TUNEL assays to demonstrate that apoptosis in the syncytiotrophoblast cells remained low at term, whereas, for the cytotrophoblast cells, apoptosis reached its nadir during the second trimester and then increased threefold to fourfold at term. 51 Magee et al 52 confirmed significant levels of TUNEL-positive cells and proapoptotic proteins (including Fas, FasL, caspase, and PARP) in term human placentas; interestingly, the apoptosis markers were significantly decreased in placentas from pregnancies complicated by gestational diabetes. As described by Zhou et al, 53 the levels of apoptosis (as indicated by TUNEL assays) were fivefold higher in term placentas from women in labor compared to those not in labor, and 15-fold higher in placentas from women whose pregnancies were complicated by preterm labor.…”

2-Arachidonoylglycerol effects in cytotrophoblasts: metabolic enzymes expression and apoptosis in BeWo cells

“…Moreover, members of the Bcl-2 family are differently expressed during the gestational period in cytotrophoblasts and syncytiotrophoblasts (Ishihara et al 2000, De Falco et al 2001, with alterations in their expression being described in some pathophysiological situations such as pre-eclampsia, IUGR and hyperglycaemia (Sgarbosa et al 2006, Longtine et al 2012b, Borzsonyi et al 2013. Therefore, it seems that anomalies in cell death regulation through the mitochondrial pathway of apoptosis may be involved in pregnancy complications.…”