Stromal cell–specific apoptotic and antiestrogenic mechanisms may explain uterine defects in humans after clomiphene citrate therapy - 19/08/11
Reprints: Ruijin Shao, MD, PhD, Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Gothenburg University, Medicinareg 11, PO Box 434, 413 90 Gothenburg, SwedenRésumé |
Objective |
The purpose of this study was to investigate clomiphene citrate (CC)–induced modulation of uterine cell function in vivo.
Study Design |
Prepubertal female Sprague-Dawley rats were treated intraperitoneally with CC for 6 or 24 hours or with a combination of CC and/or 17-β-estradiol (E2) for 4 days.
Results |
Chronic CC treatment induced apoptosis in a fraction of uterine stromal cells by activating the caspase-3-mediated apoptotic pathway. The damage was prevented by successive E2 treatment; however, pretreatment or concomitant treatment with E2 did not protect against CC-induced uterine apoptosis. CC decreased the protein expression of estrogen receptor ⍺ and increased its phosphorylation but did not affect estrogen receptor β expression or phosphorylation. Furthermore, changes in Hoxa11, p27, and progesterone receptor protein levels and localization were associated with CC treatment.
Conclusion |
We provide novel mechanistic insights into cellular and molecular events by which CC regulates uterine stromal cell function and hence the implantation process and pregnancy outcome.
Le texte complet de cet article est disponible en PDF.Key words : apoptosis, clomiphene citrate, implantation, uterus
Plan
| This study was supported by the Swedish Medical Research Council (Grant no. 5859), the Svenska Sällskapet för Medicinsk Forskning, Sahlgrenska Academy Research Council, Göteborgs Läkaresällskap, Fred G. and Emma E. Kanolds Stiftelse, Anna Cederbergs Stiftelse, Fredrik and Ingrid Thurings Stiftelse, and the Hjalmar Svenssons Research Foundation. |
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| Cite this article as: Nutu M, Feng Y, Egecioglu E, et al. Stromal cell–specific apoptotic and antiestrogenic mechanisms may explain uterine defects in humans after clomiphene citrate therapy. Am J Obstet Gynecol 2010;203:65.e1-10. |
Vol 203 - N° 1
P. 65.e1-65.e10 - juillet 2010 Retour au numéro
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