Abortion is associated with increased expression of FasL in decidual leukocytes and apoptosis of extravillous trophoblasts: a role for CRH and urocortin.
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.
Minas
V
V
Laboratory of Human Reproduction, Department of Obstetrics and Gynaecology, Medical School, University of Crete, Heraklion, Greece.
Jeschke
U
U
Kalantaridou
S N
SN
Richter
D U
DU
Reimer
T
T
Mylonas
I
I
Friese
K
K
Makrigiannakis
A
A
D000028:Abortion, Induced; D000022:Abortion, Spontaneous / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D000328:Adult; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*; D054832:Urocortins / Q000235:genetics / Q000378:metabolism / Q000502:physiology
D053222:Fas Ligand Protein; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone