title: The placenta: phenotypic and epigenetic modifications induced by Assisted Reproductive Technologies throughout pregnancy.
abstract: Today, there is growing interest in the potential epigenetic risk related to assisted reproductive technologies (ART). Much evidence in the literature supports the hypothesis that adverse pregnancy outcomes linked to ART are associated with abnormal trophoblastic invasion. The aim of this review is to investigate the relationship between epigenetic dysregulation caused by ART and subsequent placental response. The dialogue between the endometrium and the embryo is a crucial step to achieve successful trophoblastic invasion, thus ensuring a non-complicated pregnancy and healthy offspring. However, as described in this review, ART could impair both actors involved in this dialogue. First, ART may induce epigenetic defects in the conceptus by modifying the embryo environment. Second, as a result of hormone treatments, ART may impair endometrial receptivity. In some cases, it results in embryonic growth arrest but, when the development of the embryo continues, the placenta could bring adaptive responses throughout pregnancy. Amongst the different mechanisms, epigenetics, especially thanks to a finely tuned network of imprinted genes stimulated by foetal signals, may modify nutrient transfer, placental growth and vascularization. If these coping mechanisms are overwhelmed, improper maternal-foetal exchanges occur, potentially leading to adverse pregnancy outcomes such as abortion, preeclampsia or intra-uterine growth restriction. But in most cases, successful placental adaptation enables normal progress of the pregnancy. Nevertheless, the risks induced by these modifications during pregnancy are not fully understood. Metabolic diseases later in life could be exacerbated through the memory of epigenetic adaptation mechanisms established during pregnancy. Thus, more research is still needed to better understand abnormal interactions between the embryo and the milieu in artificial conditions. As trophectoderm cells are in direct contact with the environment, they deserve to be studied in more detail. The ultimate goal of these studies will be to render ART protocols safer. Optimization of the environment will be the key to improving the dialogue between the endometrium and embryo, so as to ensure that placentation after ART is similar to that following natural conception.
authors: Hôpital de Dijon, Université de Bourgogne, Service de Gynécologie-Obstétrique, Médecine Fœtale et Stérilité Conjugale, 21079 Dijon, France ; Equipe GAD, Génétique des Anomalies du Développement, EA 4271, Université de Bourgogne, Dijon, France.
authors: Cécile
authors: C
authors: Choux
authors: Equipe GAD, Génétique des Anomalies du Développement, EA 4271, Université de Bourgogne, Dijon, France.
authors: Virginie
authors: V
authors: Carmignac
authors: Equipe GAD, Génétique des Anomalies du Développement, EA 4271, Université de Bourgogne, Dijon, France ; Hôpital de Dijon, Université de Bourgogne, Laboratoire de Biologie de la Reproduction, 21079 Dijon, France.
authors: Céline
authors: C
authors: Bruno
authors: Hôpital de Dijon, Université de Bourgogne, Service de Gynécologie-Obstétrique, Médecine Fœtale et Stérilité Conjugale, 21079 Dijon, France.
authors: Paul
authors: P
authors: Sagot
authors: Institut Cochin, Team Epigénétique et Physiopathologie de la Reproduction, U1016 Inserm/UMR8104 CNRS/UMR-S8104, 24, rue du Faubourg St Jacques, 75014 Paris, France.
authors: Daniel
authors: D
authors: Vaiman
authors: Equipe GAD, Génétique des Anomalies du Développement, EA 4271, Université de Bourgogne, Dijon, France ; Hôpital de Dijon, Université de Bourgogne, Laboratoire de Biologie de la Reproduction, 21079 Dijon, France.
authors: Patricia
authors: P
authors: Fauque
keywords: Assisted Reproductive Technologies; Epigenetic; Imprinted gene; Placenta; Pregnancy