Mifepristone, but not levonorgestrel, inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model.
BACKGROUND
The use of fertility regulating drugs is limited among various socio-ethnic groups due to limited knowledge about their mechanism of action. This study investigates the effect of levonorgestrel and mifepristone on attachment of human embryos to an in vitro endometrial construct.


METHODS
Three-dimensional endometrial constructs were established by co-culturing early luteal phase human endometrial stromal and epithelial cells. Expression of endometrial receptivity markers in this construct were examined by immunohistochemistry. Effects of mifepristone and levonorgestrel on viability and attachment of human blastocysts were investigated.


RESULTS
Endometrial constructs expressed the factors involved in endometrial receptivity: estrogen receptor, progesterone receptor, vascular endothelial growth factor, leukemia inhibitory factor, interleukin-1, COX-2, MUC-1 and integrin-alpha(V)beta(3). None of the 15 embryos cultured with mifepristone attached to the endometrial construct (P < 0.01), whereas 10/17 in control, and 6/14 in levonorgestrel, groups attached. The attachment was confirmed by the positive expression of cytokeratin 7 at the attachment site.


CONCLUSIONS
Mifepristone inhibits blastocyst attachment. Levonorgestrel did not impair the attachment of human embryos to the in vitro endometrial construct. This model could be used to understand endometrial receptivity and embryo-endometrial dialog and to develop new fertility regulating substances.
Lalitkumar
P G L
PG
Division of Obstetrics and Gynecology, Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital, S-171 76, Stockholm, Sweden.
Lalitkumar
S
S
Meng
C X
CX
Stavreus-Evers
A
A
Hambiliki
F
F
Bentin-Ley
U
U
Gemzell-Danielsson
Kristina
K
D000328:Adult; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects*; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003271:Contraceptive Agents, Female / Q000494:pharmacology; D004717:Endometrium / Q000187:drug effects*; D005260:Female; D005786:Gene Expression Regulation; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016912:Levonorgestrel / Q000494:pharmacology*; D015735:Mifepristone / Q000494:pharmacology*; D014327:Trophoblasts / Q000166:cytology
D003271:Contraceptive Agents, Female; D006727:Hormone Antagonists; D015735:Mifepristone; D016912:Levonorgestrel