title: Peri-implantation hormonal milieu: elucidating mechanisms of abnormal placentation and fetal growth.
abstract: Assisted reproductive technologies (ART) have been associated with several adverse perinatal outcomes involving placentation and fetal growth. It is critical to examine each intervention individually in order to assess its relationship to the described adverse perinatal outcomes. One intervention ubiquitously used in ART is superovulation with gonadotropins. Superovulation results in significant changes in the hormonal milieu, which persist during the peri-implantation and early placentation periods. Epidemiologic evidence suggests that the treatment-induced peri-implantation maternal environment plays a critical role in perinatal outcomes. In this study, using the mouse model, we have isolated the exposure to the peri-implantation period, and we examine the effect of superovulation on placentation and fetal growth. We report that the nonphysiologic peri-implantation maternal hormonal environment resulting from gonadotropin stimulation appears to have a direct effect on fetal growth, trophoblast differentiation, and gene expression. This appears to be mediated, at least in part, through trophoblast expansion and invasion. Although the specific molecular and cellular mechanism(s) leading to these observations remain to be elucidated, identifying this modifiable risk factor will not only allow us to improve perinatal outcomes with ART, but help us understand the pathophysiology contributing to these outcomes.
authors.affiliation: Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Monica A
authors.initials: MA
authors.lastname: Mainigi
authors.forename: Devvora
authors.initials: D
authors.lastname: Olalere
authors.forename: Irina
authors.initials: I
authors.lastname: Burd
authors.forename: Carmen
authors.initials: C
authors.lastname: Sapienza
authors.forename: Marisa
authors.initials: M
authors.lastname: Bartolomei
authors.forename: Christos
authors.initials: C
authors.lastname: Coutifaris
mesh_terms: D000818:Animals; D060833:Cellular Microenvironment / Q000187:drug effects / Q000502:physiology; D010064:Embryo Implantation; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects* / Q000502:physiology; D006062:Gonadotropins / Q000009:adverse effects* / Q000097:blood; D006728:Hormones / Q000097:blood* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000166:cytology / Q000473:pathology; D010922:Placenta Diseases / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D010929:Placentation / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D015398:Signal Transduction / Q000187:drug effects; D013480:Superovulation / Q000097:blood* / Q000502:physiology
chemical_list: D006062:Gonadotropins; D006728:Hormones
keywords: ART; epigenetics; estradiol; gonadotropins; implantation