Abortion is associated with increased expression of FasL in decidual leukocytes and apoptosis of extravillous trophoblasts: a role for CRH and urocortin

Abstract

Human reproduction is remarkably inefficient, with more than half of spontaneous conceptions failing to complete the first trimester. However, little is known on the molecular events that take place at the implantation site during abortion. Here, we examined the hypothesis that the expression of the proapoptotic Fas/FasL system at the implantation site is impaired in abortions. We found that, in contrast to normal pregnancy, abortive deciduas contain leukocytes that are positive for FasL and extravillous trophoblasts (EVTs), which show increased expression of Fas and increased rates of apoptosis. In addition, the neuropeptides, corticotropin-releasing hormone and urocortin, were elevated in placental material obtained from abortions. In vitro, these peptides induced the expression of FasL in decidual lymphocytes (DL) obtained from elective termination of pregnancy placentas and thus potentiated the cells' ability to induce Fas-mediated apoptosis in an EVT-based hybridoma cell line. Finally, DL from abortion sites effectively induced apoptosis of EVT without prior treatment. It is possible that these events may impede successful early placentation and thus contribute to the pathophysiology of human abortion.

Retinoid X receptor α and retinoids are key regulators in apoptosis of trophoblasts of patients with recurrent miscarriages

“…We previously described that upregulation of apoptotic EVT is found in abortive placenta tissue (Minas et al 2007). In addition, we could show that EVT in placentas of miscarriages show a significantly higher expression of RXRa in comparison to EVT in placentas of elective terminations of healthy pregnancies (Toth et al 2008).…”

“…In addition, we could show that EVT in placentas of miscarriages show a significantly higher expression of RXRa in comparison to EVT in placentas of elective terminations of healthy pregnancies (Toth et al 2008). We also speculated that the time span between abortion and formalin fixation or freezing of the tissue samples does not lead to an additional upregulation of apoptotic EVT (Minas et al 2007). If apoptosis of EVT was due to degradation of the extracted tissue, a higher apoptosis rate would have been observed in the tissue samples of elective terminations, as those samples have been processed exactly the same way as the tissue samples from miscarriages (Minas et al 2007).…”

“…In 2007, we could also demonstrate that an increased number of apoptotic EVT is found in placentas of miscarriages in comparison to EVT of placentas from healthy pregnancy terminations (Minas et al 2007). Trophoblasts react to maternal immunological dysregulation by activation of the intrauterine pro-apoptotic Fas/Fas ligand (FasL) system (Minas et al 2007).…”

“…Trophoblasts react to maternal immunological dysregulation by activation of the intrauterine pro-apoptotic Fas/Fas ligand (FasL) system (Minas et al 2007). We further observed that an increased expression of FasL is associated with miscarriages (Minas et al 2007).…”

“…Trophoblasts react to maternal immunological dysregulation by activation of the intrauterine pro-apoptotic Fas/Fas ligand (FasL) system (Minas et al 2007). We further observed that an increased expression of FasL is associated with miscarriages (Minas et al 2007). EVT probably synthesize FasL, which induces apoptosis of activated T-cells, in order to maintain early pregnancy (Runic et al 1996, Uckan et al 1997, Kauma et al 1999, Makrigiannakis et al 2001, Abrahams et al 2004.…”