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Maternal cadmium exposure in the mouse leads to increased heart weight at birth and programs susceptibility to hypertension in adulthood.

ABSTRACT: Cadmium (Cd) is a toxic heavy metal ubiquitous in the environment. Maternal exposure to Cd is associated with fetal growth restriction, trace element deficiencies, and congenital malformations. Cd exposure during adulthood is associated with cardiovascular disease (CVD); however, the effects of maternal Cd exposure on offspring cardiovascular development and disease are not well-understood. Utilizing a mouse model of maternal Cd exposure, we show that offspring born to Cd-exposed mothers have increased heart weights at birth and susceptibility to hypertension during adulthood. Despite inefficient maternal-fetal transfer of Cd, maternal Cd alters fetal levels of essential trace elements including a deficiency in iron, which is required for cardiovascular system development, oxygen homeostasis, and cellular metabolism. RNA-seq on newborn hearts identifies differentially expressed genes associated with maternal Cd exposure that are enriched for functions in CVD, hypertension, enlarged hearts, cellular energy, and hypoxic stress. We propose that a maternal Cd exposure-induced iron deficiency leads to altered cellular metabolic pathways and hypoxic conditions during fetal development; this stress may contribute to increased heart weight at birth and the programming of susceptibility to hypertension in adulthood. These studies will give insights into potential mechanisms through which maternal Cd exposure impacts cardiovascular development and disease.

SUBMITTER: Hudson KM

PROVIDER: S-EPMC6753073 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Maternal cadmium exposure in the mouse leads to increased heart weight at birth and programs susceptibility to hypertension in adulthood.

Hudson Kathleen M KM Belcher Scott M SM Cowley Michael M

Scientific reports 20190919 1

Cadmium (Cd) is a toxic heavy metal ubiquitous in the environment. Maternal exposure to Cd is associated with fetal growth restriction, trace element deficiencies, and congenital malformations. Cd exposure during adulthood is associated with cardiovascular disease (CVD); however, the effects of maternal Cd exposure on offspring cardiovascular development and disease are not well-understood. Utilizing a mouse model of maternal Cd exposure, we show that offspring born to Cd-exposed mothers have in ...[more]

PMID: 31537853

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Project description:Fetal alcohol-related growth restriction persists through infancy, but its impact later in life is less clear. Animal studies have demonstrated important roles for maternal nutrition in fetal alcohol spectrum disorders, but the impact of prenatal maternal body composition has not been studied in humans. This study examined the effects of prenatal alcohol exposure on longitudinal growth from birth through young adulthood and the degree to which maternal weight and body mass index (BMI) moderate these effects.Nearly 480 mothers were recruited at their first prenatal clinic visit to overrepresent moderate-to-heavy use of alcohol during pregnancy, including a 5% random sample of low-level drinkers and abstainers. They were interviewed at every prenatal visit about their alcohol consumption using a timeline follow-back approach. Their children were examined for weight, length/height, and head circumference at birth, 6.5 and 13 months, and 7.5, 14, and 19 years.In multiple regression models with repeated measures (adjusted for confounders), prenatal alcohol exposure was associated with longitudinal reductions in weight, height, and weight-for-length/BMI that were largely determined at birth. At low-to-moderate levels of exposure, these effects were more severe in infancy than in later childhood. By contrast, effects persisted among children whose mothers drank at least monthly and among those born to women with alcohol abuse and/or dependence who had consumed ? 4 drinks/occasion. In addition, effects on weight, height, and head circumference were markedly stronger among children born to mothers with lower prepregnancy weight.These findings confirm prior studies demonstrating alcohol-related reductions in weight, height, weight-for-height/BMI, and head circumference that persist through young adulthood. Stronger effects were seen among children born to mothers with smaller prepregnancy weight, which may have been because of attainment of higher blood alcohol concentrations in smaller mothers for a given amount of alcohol intake or to increased vulnerability in infants born to women with poorer nutrition.

Dataset Information

Maternal cadmium exposure in the mouse leads to increased heart weight at birth and programs susceptibility to hypertension in adulthood.

Publications

Maternal cadmium exposure in the mouse leads to increased heart weight at birth and programs susceptibility to hypertension in adulthood.

Similar Datasets

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