Dataset Information

Maternal high-fat diet during pregnancy with concurrent phthalate exposure leads to abnormal placentation.

ABSTRACT: Di(2-ethylhexyl) phthalate (DEHP) is a synthetic chemical commonly used for its plasticizing capabilities. Because of the extensive production and use of DEHP, humans are exposed to this chemical daily. Diet is a significant exposure pathway and fatty food contain the highest level of phthalates. The impact on pregnancy following DEHP exposure and the associated interaction of high fat (HF) diet remains unknown. Here we report that exposure of pregnant mice to an environmentally relevant level of DEHP did not affect pregnancy. In contrast, mice fed a HF diet during gestation and exposed to the same level of DEHP display marked impairment in placental development, resulting in poor pregnancy outcomes. Our study further reveals that DEHP exposure combined with a HF diet interfere with the signaling pathway controlled by nuclear receptor PPARγ to adversely affect differentiation of trophoblast cells, leading to compromised vascularization and glucose transport in the placenta. Collectively, these findings demonstrate that maternal diet during pregnancy is a critical factor that determines whether exposure to an environmental toxicant results in impaired placental and fetal development, causing intrauterine growth restriction, fetal morbidity, and mortality.

SUBMITTER: Kannan A

PROVIDER: S-EPMC8368193 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Maternal high-fat diet during pregnancy with concurrent phthalate exposure leads to abnormal placentation.

Kannan Athilakshmi A Davila Juanmahel J Gao Liying L Rattan Saniya S Flaws Jodi A JA Bagchi Milan K MK Bagchi Indrani C IC

Scientific reports 20210816 1

Di(2-ethylhexyl) phthalate (DEHP) is a synthetic chemical commonly used for its plasticizing capabilities. Because of the extensive production and use of DEHP, humans are exposed to this chemical daily. Diet is a significant exposure pathway and fatty food contain the highest level of phthalates. The impact on pregnancy following DEHP exposure and the associated interaction of high fat (HF) diet remains unknown. Here we report that exposure of pregnant mice to an environmentally relevant level o ...[more]

PMID: 34400704

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Project description:The risk of obesity in adulthood is subject to programming beginning at conception. In animal models, exposure to maternal obesity and high fat diets influences the risk of obesity in the offspring. Among other long-term changes, offspring from obese rats develop hyperinsulinemia, hepatic steatosis, and lipogenic gene expression in the liver at weaning. However, the precise underlying mechanisms leading to metabolic dysregulation in the offspring remains unclear. Using a rat model of overfeeding-induced obesity, we previously demonstrated that exposure to maternal obesity from pre-conception to birth, is sufficient to program increased obesity risk in the offspring. Offspring of obese rat dams gain greater body weight and fat mass when fed high fat diet (HFD) as compared to lean dam. Since, disruptions of diurnal circadian rhythm are known to detrimentally impact metabolically active tissues such as liver, we examined the hypothesis that maternal obesity leads to perturbations of core clock components and thus energy metabolism in offspring liver. Offspring from lean and obese dams were examined at post-natal day 35, following a short (2 wk) HFD challenge. Hepatic mRNA expression of circadian (CLOCK, BMAL1, REV-ERBα, CRY, PER) and metabolic (PPARα, SIRT1) genes were strongly suppressed in offspring exposed to both maternal obesity and HFD. Using a mathematical model, we identified two distinct biological mechanisms that modulate PPARα mRNA expression: i) decreased mRNA synthesis rates; and ii) increased non-specific mRNA degradation rate. Moreover, our findings demonstrate that changes in PPARα transcription were associated with epigenomic alterations in H3K4me3 and H3K27me3 histone marks near the PPARα transcription start site. Our findings indicated that offspring from obese rat dams have detrimental alternations to circadian machinery that may contribute to impaired liver metabolism in response to HFD, specifically via reduced PPARα expression prior to obesity development.

Dataset Information

Maternal high-fat diet during pregnancy with concurrent phthalate exposure leads to abnormal placentation.

Publications

Maternal high-fat diet during pregnancy with concurrent phthalate exposure leads to abnormal placentation.

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