Epigenetically regulated imprinted gene expression associated with IVF and infertility: possible influence of prenatal stress and depression

Abstract

Purpose: Despite the growing body of research implying an impact of in vitro fertilization (IVF) on imprinted genes and epigenetics, few studies have examined the effects of underlying subfertility or prenatal stress on epigenetics, particularly in terms of their role in determining infant birthweights. Both subfertility and prenatal stressors have been found to impact epigenetics and may be confounding the effect of IVF on epigenetics and imprinted genes. Like IVF, both of these exposures-infertility and prenatal stressors-have been associated with lower infant birthweights. The placenta, and specifically epigenetically regulated placental imprinted genes, provides an ideal but understudied mechanism for evaluating the relationship between underlying genetics, environmental exposures, and birthweight.

Methods and results: In this review, we discuss the impacts of IVF and infertility on birthweight, epigenetic mechanisms and genomic imprinting, and the role of these mechanisms in the IVF population and discuss the role and importance of the placenta in infant development. We then highlight recent work on the relationships between infertility, IVF, and prenatal stressors in terms of placental imprinting.

Conclusions: In combination, the studies discussed, as well as two recent projects of our own on placental imprinted gene expression, suggest that lower birthweights in IVF infants are secondary to a combination of exposures including the infertility and prenatal stress that couples undergoing IVF are experiencing. The work highlighted herein emphasizes the need for appropriate control populations that take infertility into account and also for consideration of prenatal psychosocial stressors as confounders and causes of variation in IVF infant outcomes.

Keywords: Epigenetics; Imprinted genes; Placenta; Prenatal anxiety; Prenatal depression; Subfertility/infertility.

Fig. 1

Venn diagram showing similarities and differences in genes identified as being differentially expressed between those with infertility and the controls and genes differentially expressed in those with both depression and anxiety during pregnancy