Transcriptomic evidence that cortisol alters perinatal epicardial adipose tissue maturation

Abstract

Cortisol administration during late gestation in ewes, modeling maternal stress, resulted in transcriptomic changes suggesting altered maturation and metabolic changes to the offspring heart. This study investigates the effects of cortisol on epicardial adipose tissue (EAT), a visceral fat pad associated with adverse cardiovascular conditions in adults. Pregnant ewes were treated with either 1 mg·kg−1·day−1 cortisol from 115 days gestation to term and EAT collected from term fetuses (control: n = 8, maternal cortisol 1 mg·kg−1·day−1: n = 6). To compare the effects of cortisol to the normal maturation in EAT, we also modeled the normal changes in gene expression in EAT at the transition from in utero to postnatal life using the EAT from control fetuses and from two-week-old lambs (control: n = 7). Transcriptomic modeling was used to identify pathways altered by maternal cortisol overexposure. Transcriptomic modeling confirmed the brown fat phenotype of EAT at term and a transition toward white fat at 2 wk of age in EAT of control fetuses/lambs and highlighted a role of immune responses, including complement coagulation, and serotonin in this transition. Maternal cortisol (1 mg·kg−1·day−1) increased the lipid peroxidation product 4-hydroxynonenal in EAT of term fetuses but did not affect the number of activated macrophages or size of the lipid droplets in the depot; transcriptomics suggested an earlier metabolic maturation of EAT via, in part, increased immune responses.

Prevention of transgenerational transmission of disease susceptibility through perinatal intervention

“…Prenatal cortisol exposure was shown to have a significant effect on adipose differentiation in the fetus. Richards et al have reported the effects of cortisol on epicardial adipose tissue, a visceral fat pad associated with adverse cardiovascular conditions in adults, using ewe model [91], and discuss the effects of maternal cortisol. They explained that maternal cortisol differs substantially from maternal nutritional and placentalrestricted cortisol, which influences changes in the adipocytokines in parallel with feeding the fetus.…”

“…According to the Dutch Hunger Winter studies, individuals whose mothers were pregnant during the famine had higher methylation of some genes and lower methylation of others as compared with those who were not prenatally exposed to famine [44,88,89]. These methylation differences may explain the likelihood of these individuals developing certain diseases later in life [90][91][92]. To further examine these changes, we will be conducting more wide-ranging and comprehensive epigenomic analyses in order to elucidate the mechanisms by which the effects of fetal undernutrition are inherited intergenerationally and transgenerationally (Fig.…”