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Updated: Jun 12, 2026

Two Methods for Establishing Primary Human Endometrial Stromal Cells from Hysterectomy Specimens
Published on: May 23, 2014
Stromal cell-specific apoptotic and antiestrogenic mechanisms may explain uterine defects in humans after clomiphene
Magdalena Nutu1, Yi Feng, Emil Egecioglu
1Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
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-beta-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 alpha and increased its phosphorylation but did not affect estrogen receptor beta 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.
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