Placental protection of the fetal brain during short-term food deprivation

Abstract

The fetal genome regulates maternal physiology and behavior via its placenta, which produces hormones that act on the maternal hypothalamus. At the same time, the fetus itself develops a hypothalamus. In this study we show that many of the genes that regulate placental development also regulate the developing hypothalamus, and in mouse the coexpression of these genes is particularly high on embryonic days 12 and 13 (days E12-13). Such synchronized expression is regulated, in part, by the maternally imprinted gene, paternally expressed gene 3 (Peg3), which also is developmentally coexpressed in the hypothalamus and placenta at days E12-13. We further show that challenging this genomic linkage of hypothalamus and placenta with 24-h food deprivation results in disruption to coexpressed genes, primarily by affecting placental gene expression. Food deprivation also produces a significant decrease in Peg3 gene expression in the placenta, with consequences similar to many of the placental gene changes induced by Peg3 mutation. Such genomic dysregulation does not occur in the hypothalamus, where Peg3 expression increases with food deprivation. Thus, changes in gene expression brought about by food deprivation are consistent with the fetal genome's maintaining hypothalamic development at a cost to its placenta. This biased change to gene dysregulation in the placenta is linked to autophagy and ribosomal turnover, which sustain, in the short term, nutrient supply for the developing hypothalamus. Thus, the fetus controls its own destiny in times of acute starvation by short-term sacrifice of the placenta to preserve brain development.genomic imprinting | mother infant coadaptation

5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats

“…In our study the impact of maternal LP diet on 5-HT was more pronounced in the placenta and fetal brain than in the dam. This supports the proposal that, the placenta is cannibalized in response to maternal food deprivation to provide nutrients and substrates for the developing hypothalamus (Broad and Keverne, 2011). We observed an association between placental 5-HT and fetal brain 5-HT at E16.5, the time-point at which 5-HT fibres can be detected in the hypothalamus and both exogenous and endogenous sources of 5-HT contribute to fetal 5-HT synthesis (Aitken and Tork, 1988;.…”

Roles of the placenta in fetal brain development

“…There is a growing appreciation that perturbations in the maternal environment are conveyed to the fetus by changes in placental function (4). Two recent studies have identified functions of the murine placenta as the interface between the maternal environment and the developing CNS (5,6). In response to acute maternal food deprivation, Broad and Keverne (5) find that a program of catabolic gene expression is initiated in the placenta, whereas the hypothalamus is largely spared.…”

Targeted placental deletion of OGT recapitulates the prenatal stress phenotype including hypothalamic mitochondrial dysfunction

“…Examination of the placenta is a promising avenue to find these mechanisms and biomarkers because of features of its biology and accessibility for diagnostic purposes postparturition. The placenta is uniquely positioned at the interface between the maternal and fetal compartments and is rapidly developing during the period of gestation at which maternal stress has been identified to increase disease risk to the offspring (1)(2)(3)(4)(5). We previously identified a reduction in O-GlcNAc transferase (OGT), an important O-glycotransferase enzyme that plays a critical role in regulation of gene expression through chromatin remodeling, in male placentas following early prenatal stress (EPS) (4).…”