title: Effects of low doses of mifepristone on human embryo implantation process in a three-dimensional human endometrial in vitro co-culture system.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet/Karolinska University Hospital, S-171 76, Stockholm, Sweden.
authors.forename: N R
authors.initials: NR
authors.lastname: Boggavarapu
authors.affiliation: Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet/Karolinska University Hospital, S-171 76, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Berger
authors.affiliation: Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet/Karolinska University Hospital, S-171 76, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: von Grothusen
authors.affiliation: Fertilitetscentrum, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Menezes
authors.affiliation: Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet/Karolinska University Hospital, S-171 76, Stockholm, Sweden. Electronic address: kristina.gemzell@ki.se.
authors.forename: K
authors.initials: K
authors.lastname: Gemzell-Danielsson
authors.affiliation: Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet/Karolinska University Hospital, S-171 76, Stockholm, Sweden. Electronic address: lalit.kumar@ki.se.
authors.forename: P G L
authors.initials: PG
authors.lastname: Lalitkumar
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D018920:Coculture Techniques; D044363:Contraception, Postcoital; D010064:Embryo Implantation / Q000187:drug effects*; D004717:Endometrium / Q000187:drug effects*; D005260:Female; D006727:Hormone Antagonists / Q000008:administration & dosage*; D006801:Humans; D015735:Mifepristone / Q000008:administration & dosage*; D011374:Progesterone / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013548:Sweden; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006727:Hormone Antagonists; D015735:Mifepristone; D011374:Progesterone
keywords: Contraception; Embryo implantation; Emergency contraception; Endometrial receptivity; Mifepristone; Progesterone receptor modulator