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Effects of low doses of mifepristone on human embryo implantation process in a three-dimensional human endometrial in vitro co-culture system.

Abstract：

OBJECTIVES:We wanted to explore the effects of two different low doses (0.5μM and 0.05μM) of mifepristone, exposed during the receptive period, on the human embryo implantation process, using a well-established three-dimensional in vitro cell culture model, specifically developed to study this process. METHODS:An in vitro three-dimensional cell culture model was constructed using human endometrial cells isolated from the endometrium of proven fertile women, collected on cycle day LH+4. After 5 days of culture, supernumerary human embryos were added and cultured for another 5 days with mifepristone 0.5μM (n=8) or 0.05μM (n=10) or vehicle as control (n=10). The cultures were checked for embryo attachment and terminated. We studied the expression of 16 reported endometrial receptivity markers in the endometrial constructs using real-time polymerase chain reaction. RESULTS:None of the embryos in 0.5μM of mifepristone attached to the endometrial constructs (p=.004), whereas 4 out of 10 in 0.05μM (p=.3698) and 7 out of 10 embryos in the control group attached to the cultures. We found that most of the studied receptivity markers were significantly altered with mifepristone exposure in a similar direction in both treatment groups. Only IL6 was significantly differentially expressed between the treatment groups (p=.017). CONCLUSION:We report for the first time that exposure to a low concentration (0.5μM) of mifepristone during the receptive period successfully inhibits human embryo implantation process in vitro. Further, we observed a dose-dependent effect of mifepristone on endometrial receptivity at the functional level. IMPLICATION:This study contributes new knowledge that low dose of mifepristone during the short period of receptive phase can inhibit endometrial receptivity, which further promotes mifepristone as a contraceptive agent. This could give women a treatment choice to avoid unwanted pregnancy with high efficacy and minimal side effects.

journal_name

Contraception

journal_title

Contraception

authors

Boggavarapu NR,Berger C,von Grothusen C,Menezes J,Gemzell-Danielsson K,Lalitkumar PG

doi

10.1016/j.contraception.2016.03.009

subject

Has Abstract

pub_date

2016-08-01 00:00:00

pages

143-51

issue

eissn

0010-7824

issn

1879-0518

pii

S0010-7824(15)30213-4

journal_volume

pub_type

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Effects of low doses of mifepristone on human embryo implantation process in a three-dimensional human endometrial in vitro co-culture system.