Epigenetic remodeling of chromatin in human ART: addressing deficiencies in culture media
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REVIEW
Epigenetic remodeling of chromatin in human ART: addressing deficiencies in culture media Yves Ménézo 1
&
Kay Elder 2
Received: 3 July 2020 / Accepted: 6 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Keywords Human embryo . Culture media . Epigenetics . Methylation . Essential sulfur aminoacids . Oxidative stress
Current scientific literature increasingly documents a correlation between assisted reproductive technologies (ART) and epigenetic errors in the children born, attributed to errors in methylation affecting the embryonic genome [1–5]. The majority of the epigenetic anomalies observed to date have been largely associated with IVF/ICSI procedures themselves, rather than problems intrinsic to gametes as a result of male and/or female infertility etiology [2, 5]. For example, a recent paper describing a high incidence of four major imprinting disorders in Japanese babies born after ART suggests that the origin of these disorders may be in the period immediately following fertilization under currently used culture conditions [3, 5]; as this is the stage during which the zygote genome undergoes demethylation, any disruption to methylation maintenance makes this a likely possibility. Whether controlled ovarian hyperstimulation (COH) is linked to epigenetic errors in the offspring remains ambiguous. Although a negative correlation has been described in the mouse [6], bovine embryos provide a more appropriate model for studies of this kind until data become available for the human [7, 8]. In terms of fundamental processes involved with DNA methylation, there is greater homology between bovine and human DNA methyltransferases (DNMTs) than between mouse and human DNMTs structures. Moreover, the time course of oocyte maturation as well as imprinted gene expression and methylation patterns are conserved between humans and cattle during early development, compared with human and mouse [8], thus whether
* Yves Ménézo [email protected] Kay Elder [email protected] 1
Laboratoire Clément, 17 Avenue d’Eylau, 75016 Paris, France
2
Bourn Hall Clinic, Bourn, Cambridge CB232TN, UK
COH imparts a negative impact on the oocyte epigenome remains controversial [9]. However, the influence of culture conditions on epigenetic chromatin remodeling during pre-implantation development has become increasingly clear. In the early years of this century, well before the role of epigenetics and imprinting disorders in human ARTs was appreciated, RG Edwards voiced a suspicion that pre-implantation culture media could induce anomalies in the concepti [10]. Remarkably, despite the fact that biochemical and physiological mechanisms differ between human and mouse, and the bovine model appears to be more closely related to the human embryo [7], the mouse embryo assay (MEA) continues to be the accepted test for quality control of commercial IVF culture media, a dogma that has been contested [11]. The two features that differ most significantly are the duration of antral growth/maturation and the t
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