Apoptosis in the normal human amnion at term, independent of Bcl-2 regulation and onset of labour

Abstract

This study was designed to detect apoptosis in the human amnion and to elucidate the signalling pathway involved in its regulation. Samples of human amnion were obtained from 34 women (weeks 11-42 of gestation) and studied using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) method with light microscopy (LM) and transmission electron microscopy (TEM). Apoptotic regulators in the samples were studied by immunohistochemistry and caspase activity assay. The TUNEL method with LM demonstrated that the percentage of TUNEL-positive cells in the amniotic epithelium was the highest in weeks 40-41 of gestation (P < 0.05) independent of the onset of labour, and the cells were often detached from the epithelium into the amniotic cavity at term. The TUNEL method with TEM clearly showed the characteristic features of apoptosis such as the nuclear condensed chromatin with abundant free 3'-OH DNA ends, cell shrinkage and a decrease in the number of desmosomes, except for the presence of apoptotic bodies. Fas and Fas ligand (FasL) were constantly expressed on apical membranes of amniotic epithelial cells from weeks 16-27 through to 40-41 of gestation, while no Bcl-2 expression was observed throughout the gestational periods. Activities of caspase-3 and caspase-8, but not of caspase-9, were higher in weeks 40-41 than those from weeks 16-27 of gestation (P < 0.01). We conclude that apoptosis in term amniotic epithelium is independent of Bcl-2 regulation and onset of labour, and may play an important role in the fragility and rupture of human fetal membranes at term.

Nuclear Factor Kappa B Activation Occurs in the Amnion Prior to Labour Onset and Modulates the Expression of Numerous Labour Associated Genes

“…The first of these networks- cell death, cancer and morphology- is consistent with marked increase in apoptosis observed with the preparation of the amnion for rupture [36], [37] via the delamination and apoptosis of amnion epithelial cells (Figure 6). However, this observation contrasts with the well described role for NFκB as an anti-apoptotic transcription factor [38].…”

Amniotic membrane and placental histopathological findings after open and fetoscopic prenatal neural tube defect repair

“…In addition, there were no significant differences noted when fetoscopically repaired cases were compared with open repaired cases. Apoptosis is a type of cell death controlled by a series of molecular events and is executed by a family of cysteine‐containing aspartate‐specific proteases called the caspase family . Previous studies on patients who had undergone laser treatment for twin‐twin‐transfusion syndrome (TTTS) using TUNEL staining showed increased cell death .…”

Possible Roles of Proinflammatory and Chemoattractive Cytokines Produced by Human Fetal Membrane Cells in the Pathology of Adverse Pregnancy Outcomes Associated with Influenza Virus Infection

“…Recent studies have revealed that the number of apoptotic cells was much higher in the chorion of fetal membranes with histological chorioamnionitis at term than those without chorioamnionitis [92] and that the chorion of fetal membranes from patients with premature rupture of membranes had significantly more apoptotic cells than those without chorioamnionitis [93]. In addition, apoptosis was detected in also amnion epithelial cells at term, which was associated with onset of labor [94]. It is likely that apoptotic cell death in broad area of the fetal membranes is responsible for the rupture of fetal membranes both at term under physiological conditions and at preterm with chorioamnionitis.…”