Developmental programming: Interaction between prenatal BPA and postnatal overfeeding on cardiac tissue gene expression in female sheep

Abstract

Epidemiologic studies and studies in rodents point to potential risks from developmental exposure to BPA on cardiometabolic diseases. Furthermore, it is becoming increasingly evident that the manifestation and severity of adverse outcomes is the result of interaction between developmental insults and the prevailing environment. Consistent with this premise, recent studies in sheep found prenatal BPA treatment prevented the adverse effects of postnatal obesity in inducing hypertension. The gene networks underlying these complex interactions are not known. mRNA-seq of myocardium was performed on four groups of four female sheep to assess the effects of prenatal BPA exposure, postnatal overfeeding and their interaction on gene transcription, pathway perturbations and functional effects. The effects of prenatal exposure to BPA, postnatal overfeeding, and prenatal BPA with postnatal overfeeding all resulted in transcriptional changes (85–141 significant differentially expressed genes). Although the effects of prenatal BPA and postnatal overfeeding did not involve dysregulation of many of the same genes, they affected a remarkably similar set of biological pathways. Furthermore, an additive or synergistic effect was not found in the combined treatment group, but rather prenatal BPA treatment led to a partial reversal of the effects of overfeeding alone. Many genes previously known to be affected by BPA and involved in obesity, hypertension, or heart disease were altered following these treatments, and AP-1, EGR1, and EGFR were key hubs affected by BPA and/or overfeeding.

Developmental programming: Sex‐specific programming of growth upon prenatal bisphenol A exposure

“…As opposed to lack of effect of prenatal BPA on fetal male liver, prenatal BPA treatment increased the heart/body weight ratio at GD90 in males, alone. Consistent with the lack of effect on the female heart during fetal life, there were no effects of prenatal BPA treatment on blood pressure or morphometric measures in adult BPA‐treated offspring (Koneva et al, ; MohanKumar et al, ). However, prenatal BPA treatment upregulated several genes involved in the regulation of myocardium growth, heart development and remodeling, and the downregulation of genes involved in cellular respiration and inflammation in adult prenatal BPA‐treated females (Koneva et al, ).…”

“…Consistent with the lack of effect on the female heart during fetal life, there were no effects of prenatal BPA treatment on blood pressure or morphometric measures in adult BPA‐treated offspring (Koneva et al, ; MohanKumar et al, ). However, prenatal BPA treatment upregulated several genes involved in the regulation of myocardium growth, heart development and remodeling, and the downregulation of genes involved in cellular respiration and inflammation in adult prenatal BPA‐treated females (Koneva et al, ). Prenatal BPA treatment was also found to reduce collagen expression in the right ventricle (MohanKumar et al, ).…”

Prenatal Bisphenol a Exposure and Postnatal Trans Fat Diet Alter Small Intestinal Morphology and Its Global DNA Methylation in Male Sprague-Dawley Rats, Leading to Obesity Development

“…Importantly, previous studies have demonstrated that the postnatal environment could amplify the final phenotypic outcomes programmed by early developmental insults [27][28][29]. Nonetheless, to the best of our knowledge, no studies have reported on the responsiveness of intestinal function to postnatal insults, ensuing the metabolic disruptions programmed by prenatal BPA exposure.…”

High Fat Programming and Cardiovascular Disease

“…Maternal hyperglycemia in pregnancy is independently associated with the offspring’s risk for glucose intolerance, obesity and an increase in blood pressure in seven-year-old children, with only girls being obese [ 51 ]. In female sheep, after prenatal bisphenol A (BPA, commonly found in polycarbonate plastic and epoxy resins) exposure, postnatal overfeeding/adiposity, and the combination, led to myocardial transcriptional changes, and despite different gene profiles, still influenced similar signaling pathways [ 21 ]. Genes altered by the programming insult were implicated in obesity, hypertension or heart disease [ 21 ].…”

“…In female sheep, after prenatal bisphenol A (BPA, commonly found in polycarbonate plastic and epoxy resins) exposure, postnatal overfeeding/adiposity, and the combination, led to myocardial transcriptional changes, and despite different gene profiles, still influenced similar signaling pathways [ 21 ]. Genes altered by the programming insult were implicated in obesity, hypertension or heart disease [ 21 ]. In rats, a maternal HFD causes cardiac hypertrophy; increases cardiac susceptibility to ischemic-reperfusion injury only in adult male offspring, and differentially regulates cardiac angiotensin II (AngII) receptor type 1 (AGTR1) and type 2 (AGTR2) expression [ 48 ].…”