Imprinted gene expression in the rat embryo–fetal axis is altered in response to periconceptional maternal low protein diet

Abstract

In our previous study, we have shown that maternal low protein diet (LPD, 9% casein vs 18% casein control) fed exclusively during the rat preimplantation period (0-4.25 day postcoitum) induced low birth weight, altered postnatal growth and hypertension in a gender-specific manner. In this study, we investigated the effect of maternal LPD restricted only to the preimplantation period (switched diet) or provided throughout gestation on fetal growth and imprinted gene expression in blastocyst and fetal stages of development. Male, but not female, blastocysts collected from LPD dams displayed a significant reduction (30%) in H19 mRNA level. A significant reduction in H19 (9.4%) and Igf2 (10.9%) mRNA was also observed in male, but not in female, fetal liver at day 20 postcoitum in response to maternal LPD restricted to the preimplantation period. No effect on the blastocyst expression of Igf2R was observed in relation to maternal diet. The reduction in H19 mRNA expression did not correlate with an observed alteration in DNA methylation at the H19 differentially methylated region in fetal liver. In contrast, maternal LPD throughout 20 days of gestation did not affect male or female H19 and Igf2 imprinted gene expression in fetal liver. Neither LPD nor switched diet treatments affected H19 and Igf2 imprinted gene expression in day 20 placenta. Our findings demonstrate that one contributor to the alteration in postnatal growth induced by periconceptional maternal LPD may derive from a gender-specific programming of imprinted gene expression originating within the preimplantation embryo itself.

Sexual dimorphism in environmental epigenetic programming

“…Maternal undernutrition also led to significantly lower levels of H19 (9.4%) and Igf2 (10.9%) mRNA in male, but not in female, fetal liver. These differences may result from the sex-specific programming of imprinted gene expression within the preimplantation embryo itself [40, 75,76]. Postnatal changes in cerebral chromatin conformation in rats born with IUGR are also sex-specific [26].…”

Dietary omega-3 and -6 polyunsaturated fatty acids affect the composition and development of sheep granulosa cells, oocytes and embryos

“…RNA was extracted from pools of 10-29 ovine blastocysts using Dynabeads mRNA DIRECT kit (Invitrogen Ltd; Kwong et al 2006). RT of mRNA from blastocysts was performed using QuantiTect RT kit (Qiagen Ltd), which eliminates genomic DNA and efficiently reverse transcribes small quantities of RNA in a two-step reaction.…”

Genomic imprinting as an adaptative model of developmental plasticity

“…However, the functional significance of this is unclear as leukocyte methylation is notoriously variable and the studies did not examine any associated expression changes, effects on imprinting, or attempt any correlation with known phenotypic outcomes [43,44]. In a rat model of periimplantation low protein diet Kwong et al [36,37] demonstrated a male-specific reduction in birth weight and development of hypertension at a young age, associated with a 30% reduction in male blastocyst H19 expression. While methylation at the H19 DMR was slightly altered [37], it did not correlate with the observed change in expression, indicating that it was not mechanistically responsible and, although not directly tested, imprinting Neoplastic cell, Loss of imprinting (LOI) Slow cycling stem cell Relaxation of imprinting…”