Superovulation alters the expression of imprinted genes in the midgestation mouse placenta

Abstract

Imprinted genes play important roles in embryonic growth and development as well as in placental function. Many imprinted genes acquire their epigenetic marks during oocyte growth, and this period may be susceptible to epigenetic disruption following hormonal stimulation. Superovulation has been shown to affect growth and development of the embryo, but an effect on imprinted genes has not been shown in postimplantation embryos. In the present study, we examined the effect of superovulation/in vivo development or superovulation/3.5dpc (days post-coitum) embryo transfer on the allelic expression of Snrpn, Kcnq1ot1 and H19 in embryos and placentas at 9.5 days of gestation. Superovulation followed by in vivo development resulted in biallelic expression of Snrpn and H19 in 9.5dpc placentas while Kcnq1ot1 was not affected; in the embryos, there was normal monoallelic expression of the three imprinted genes. We did not observe significant DNA methylation perturbations in the differentially methylated regions of Snrpn or H19. Superovulation followed by embryo transfer at 3.5dpc resulted in biallelic expression of H19 in the placenta. The expression of an important growth factor closely linked to H19, Insulin-like growth factor-II, was increased in the placenta following superovulation with or without embryo transfer. These results show that both maternally and paternally methylated imprinted genes were affected, suggesting that superovulation compromises oocyte quality and interferes with the maintenance of imprinting during preimplantation development. Our findings contribute to the evidence that mechanisms for maintaining imprinting are less robust in trophectoderm-derived tissues, and have clinical implications for the screening of patients following assisted reproduction.

Negative uterine asynchrony retards early equine conceptus development and upregulation of placental imprinted genes

“…Moreover, most of the imprinted genes studied, independent of their imprinting status (maternal or paternal), suffered delayed upregulation in conceptuses transferred to an asynchronous environment, which may simply reflect developmental retardation. On the other hand, imprinted genes are known to be susceptible to epigenetic modification in response to environmental perturbations during early pregnancy [18,21,22]. To examine whether there was any rationale to suspect epigenetic alteration, we also examined expression of DNA methyltransferase genes, which regulate gene function by maintaining genome methylation (DNMT1) or establishing de novo methylations (DNMT3a and DNMT3b) [40].…”

“…Indeed, paternally expressed genes generally enhance fetal growth, whereas maternally expressed genes restrict it [20]. Moreover, recent studies have shown that environmental factors can affect early embryo development and expression of developmentally important and/or placentally imprinted genes, presumably by epigenetic dysregulation [18,21,22]. Imprinted genes may, therefore, be particularly sensitive to epigenetic alterations as a result of an inappropriate or altered environment during early embryo development [21].…”

Imprinted genes in mouse placental development and the regulation of fetal energy stores

“…No Imprinted in E10 placenta and E13 yolk sac Ono et al (2003), Wang et al (2011) and Okae et al (2012) Conflicting data from E13.5 placenta following embryo transfer to eliminate decidual contamination Biallelic in E17.5 placenta and neonate Biallelic in TS cells Lee et al (2000) and Okae et al (2012) Imprinted in embryo and brain No Imprinted in E13.5 and E17.5 placenta, embryo and neonate Kim et al (1999), Wang et al (2011) and Okae et al (2012) Biallelic in neonatal and adult brain No Imprinted in all tissues examined from wE7.5 Leff et al (1992), Barr et al (1995), Gray et al (1999), de los Santos et al (2000 and Fortier et al (2008) Placental imprinting analysis complicated by maternal contamination Imprinted in TS cells …”

Genomic imprinting as an adaptative model of developmental plasticity

“…Multiple studies of embryos fertilised and cultured in vitro have suggested that imprinting control elements may be more susceptible to the environment during this period than previously thought [38,39]. However, these studies are potentially confounded by the effects of superovulation, which has been shown to alter the epigenetic status of maternal ICRs [40].…”