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%) inH19mRNA level. A significant reduction inH19(9.4%) andIgf2(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 ofIgf2Rwas observed in relation to maternal diet. The reduction inH19mRNA expression did not correlate with an observed alteration in DNA methylation at theH19differentially methylated region in fetal liver. In contrast, maternal LPD throughout 20 days of gestation did not affect male or femaleH19andIgf2imprinted gene expression in fetal liver. Neither LPD nor switched diet treatments affectedH19andIgf2imprinted 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.