Title: Maternal cadmium exposure in the mouse leads to increased heart weight at birth and programs susceptibility to hypertension in adulthood.
Authors: Hudson, Kathleen M; Belcher, Scott M; Cowley, Michael
Published In Sci Rep, (2019 09 19)
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.
PubMed ID: 31537853
MeSH Terms: Animals; Animals, Newborn; Body Weight/drug effects; Cadmium/adverse effects*; Disease Models, Animal; Female; Gene Expression Profiling/methods; Gene Expression Regulation/drug effects; Gene Regulatory Networks/drug effects*; Heart/anatomy & histology*; Heart/drug effects; Hypotension/chemically induced; Hypotension/genetics*; Maternal Exposure/adverse effects*; Metabolic Networks and Pathways/drug effects; Mice; Organ Size/drug effects; Pregnancy; Prenatal Exposure Delayed Effects/chemically induced; Prenatal Exposure Delayed Effects/genetics*; Sequence Analysis, RNA