Molecular Human Reproduction, Vol. 7, No. 9, 867-874,
September 2001
© 2001 European Society of Human Reproduction and Embryology
Uterine physiology |
The Fas/FasL apoptotic pathway is involved in 
-opioid-induced apoptosis of human endometrial stromal cells
1 Departments of Pharmacology and 2 Clinical Chemistry, School of Medicine, University of Crete, Heraklion GR-711 10, Crete, Greece
Abstract
Human endometrium expresses specific 
-opioid binding sites and their endogenous ligands, the dynorphins. In neural crest-derived tissues, -opioids affect apoptosis, a phenomenon of major significance in endometrial stroma physiology. Our hypothesis was that endometrial -opioids may play a role in endometrial stromal cell apoptosis. Thus, we examined the effect of the synthetic -opioid agonist, U69593, on the apoptotic rate of human endometrial stromal cells in primary culture. Apoptosis of endometrial stromal cells was elevated after 3 h exposure to 100 nmol/l U69593, and remained elevated for up to 3 days. This effect was dose-dependent and was reversed by the general opioid antagonist, naloxone, suggesting that it is mediated via opioid receptors. In parallel, semi-quantitative Western blot and flow cytometry analysis showed that U69593 caused a rapid but transient up-regulation of Fas protein, suggesting that its effect on apoptosis is mediated by activation of the Fas/FasL apoptotic pathway. Additionally, U69593 increased the content of the anti-apoptotic members of the Bcl-2 family of proteins, the Bcl-2 and Bcl-xL, whereas it had no significant effect on the apoptosis-promoting homologues Bax, Bcl-xS and Bak. This implies that a transient survival mechanism is activated in stromal cells as a parallel rescue response to the apoptosis-inducing factor. In conclusion, our data suggest that endometrial opioid dynorphins may participate in the apoptotic processes related to endometrial tissue remodelling during early pregnancy or menstruation.
apoptosis/Bcl-2/endometrium/Fas/FasL/-opioids
Notes
3 To whom correspondence should be addressed. E-mail: gravanis{at}med.uoc.gr
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