In vitro fertilization (IVF) in mammals: epigenetic and developmental alterations. Scientific and bioethical implications for IVF in humans

Abstract

The advent of in vitro fertilization (IVF) in animals and humans implies an extraordinary change in the environment where the beginning of a new organism takes place. In mammals fertilization occurs in the maternal oviduct, where there are unique conditions for guaranteeing the encounter of the gametes and the first stages of development of the embryo and thus its future. During this period a major epigenetic reprogramming takes place that is crucial for the normal fate of the embryo. This epigenetic reprogramming is very vulnerable to changes in environmental conditions such as the ones implied in IVF, including in vitro culture, nutrition, light, temperature, oxygen tension, embryo-maternal signaling, and the general absence of protection against foreign elements that could affect the stability of this process. The objective of this review is to update the impact of the various conditions inherent in the use of IVF on the epigenetic profile and outcomes of mammalian embryos, including superovulation, IVF technique, embryo culture and manipulation and absence of embryo-maternal signaling. It also covers the possible transgenerational inheritance of the epigenetic alterations associated with assisted reproductive technologies (ART), including its phenotypic consequences as is in the case of the large offspring syndrome (LOS). Finally, the important scientific and bioethical implications of the results found in animals are discussed in terms of the ART in humans.

Oviduct: roles in fertilization and early embryo development

“…Factors known to be different between IVF and natural development can cause epigenetic influence, including techniques, embryo culture media and environmental exposures such as tissue culture plastics (Ventura-Junca et al 2015). Bisphenol A (BPA) is known for its action as an endocrine-disrupting compound and a weak estrogen agonist/antagonist.…”

Use of FTA ® classic cards for epigenetic analysis of sperm DNA

“…Our procedure allows repeated testing over an extended time-span of many years following sample collection, especially because it has been demonstrated that methylation of sperm DNA is not subject to change over time (14). Since assisted fertilization techniques have increasingly shown problems arising after a significant time-span (15), it becomes increasingly important to monitor the methylation status of germ cell genes.…”

Children Conceived by Assisted Reproductive Technology Prone to Low Birth Weight, Preterm Birth, and Birth Defects: A Cohort Review of More Than 50,000 Live Births During 2011–2017 in Taiwan

“…The altered methylations of the endothelial nitric oxide synthase (eNOS) gene leads to decreased vascular NO synthesis in the aorta, and endothelial dysfunction and increased stiffness lead to arterial hypertension (23,24). Exogenous Gonadotropins administered to the ovary during controlled ovarian stimulation causes epigenetic changes in peg1, kcnq1ot1, zac (Zac1), and h19 (25). Zac1 plays an important role in neural stem cell quiescence, proliferation and differentiation (26).…”