Maternal food-restriction leads to a drastic downregulation of H4K16 acetylation in IUGR rat placentas

Undernutrition during gestation is associated with an increased susceptibility to metabolic and cardiovascular diseases. Placenta, as a widely recognized programming agent, contributes to the underlying processes. Alterations in both placental development and activity are well known to constitute programming events for offspring’s physiology and metabolism in adulthood. Growing experimental evidences suggest that epigenetic marks may serve as a memory of exposure to inappropriate environments and thus could be implicated in foetal programming.1 Our aim was to explore whether maternal undernutrition could disturb epigenetic processes in the placenta of intrauterine growth-restricted (IUGR) foetuses. Two experimental IUGR models were used: pregnant Wistar rats were subjected to a 70% food restriction along the gestation (FR30 model);2 or to a 50% food restriction during the last week of gestation (FR50).3 We investigated the global level of four epigenetic marks in full-term placentas. DNA methylation was assessed using LUMA and performed western blot assays for H3K9me3, H3K4me3 and H4K16ac, three important histone marks.4 We did not observe any change in H3K9me3, H3K4me3 and DNA methylation, but a decrease in placental H4K16ac, in both models and in both sexes. High-performance liquid chromatography/high-performance capillary electrophoresis quantified the decrease of H4 monoacetylation: 212% in FR30 males, 218% in FR50 males and 222% in FR30 and FR50 females. As both models were similarly affected, our findings suggest that the last third of gestation may be a critical period for H4K16ac set-up in placenta. This epigenetic mark may constitute a nutritional sensitive target during foetal programming and may be an important link between nutrition and epigenetic programming during foeto-placental development.