Effect of levonorgestrel and mifepristone on endometrial receptivity markers in a three-dimensional human endometrial cell culture model.
OBJECTIVE
To investigate the effect of levonorgestrel and mifepristone on the expression of endometrial receptivity markers in a three-dimensional endometrial construct.


METHODS
In vitro study.


METHODS
University hospital and research laboratory.


METHODS
Twelve fertile donors.


METHODS
Timed endometrial biopsy.


METHODS
Examine the effect of levonorgestrel along with another well-studied fertility-regulating drug, mifepristone, on the expression of endometrial receptivity factors in a three-dimensional stromal and epithelial cell coculture model by immunohistochemistry.


RESULTS
Both epithelial and stromal cells of in vitro endometrial construct showed the presence of estrogen receptor-alpha, estrogen receptor-beta, progesterone receptors-(A+B), vascular endothelial growth factor, leukemia inhibitory factor, interleukin-1 beta, and cyclooxygenase-2, whereas the expression of progesterone receptor-B (AR), integrin alpha(V)beta(3,) and MUC1 were confined to epithelial cells. Mifepristone up-regulated expression of epithelial estrogen receptor-beta and progesterone receptor-B and down-regulated stromal vascular endothelial growth factor and surface molecules MUC1 and integrin alpha(V)beta(3) as observed in vivo. Levonorgestrel had no effect on the expression of endometrial receptivity markers studied.


CONCLUSIONS
This in vitro model expresses progesterone-regulated endometrial receptivity factors seen in the physiologic condition. Treatment with levonorgestrel did not affect the expression of these endometrial receptivity markers in contrast to mifepristone. This in vitro model holds the potential to study endometrial receptivity, the embryo-endometrial interaction, and develop new agents for fertility control.
Meng
Chun-Xia
CX
Department of Woman and Child Health, Division of Obstetrics and Gynecology, Karolinska Institutet/Karolinska University Hospital, Stockholm, Sweden.
Andersson
Karin Louise
KL
Bentin-Ley
Ursula
U
Gemzell-Danielsson
Kristina
K
Lalitkumar
P G Luther
PG
D000328:Adult; D001706:Biopsy; D018929:Cell Culture Techniques / Q000379:methods; D018920:Coculture Techniques; D003280:Contraceptives, Oral, Synthetic / Q000494:pharmacology; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005260:Female; D005298:Fertility / Q000187:drug effects / Q000502:physiology; D006801:Humans; D016912:Levonorgestrel / Q000494:pharmacology*; D008597:Menstrual Cycle / Q000502:physiology; D015735:Mifepristone / Q000494:pharmacology*; D008954:Models, Biological; D018709:Statistics, Nonparametric; D055815:Young Adult
D003280:Contraceptives, Oral, Synthetic; D015735:Mifepristone; D016912:Levonorgestrel