Gestational arsenite exposure alters maternal postpartum heart size and induces Ca2+-handling dysregulation in cardiomyocytes.

Abstract

Cardiovascular disease is the leading cause of mortality in the US. Studies suggest a role for environmental exposures in the etiology of cardiovascular disease, including exposure to arsenic through drinking water. Arsenic exposure during pregnancy has been shown to have effects on offspring, but few studies have examined impacts on maternal cardiovascular health. While our prior work documented the detrimental effect of arsenic on the maternal heart during pregnancy, our current study examines the effect of gestational arsenic exposure on the maternal heart postpartum. Timed-pregnant wild-type (C57BL/6J) mice were exposed to 0, 100 or 1000 µg/L sodium arsenite (NaAsO2) via drinking water from embryonic day 2.5 until parturition. Postpartum heart structure and function was assessed via transthoracic echocardiography and gravimetric measurement. Hypertrophic markers were probed via qRT-PCR and western blot. Isolated cardiomyocyte Ca²⁺-handling and contraction were also assessed, along with the expression of with Ca²⁺-handling and contractile proteins. Interestingly, we found that exposure to either 100 or 1000 µg/L sodium arsenite increased postpartum heart size at postpartum day 12 vs. non-exposed postpartum controls. At the cellular level, we found altered cardiomyocyte Ca²⁺-handling and contraction, along with expression changes of key contractile proteins, including α-Actin and cardiac myosin binding protein C (cMyBP-c). Together, these findings suggest that gestational arsenic exposure impacts the postpartum maternal heart, possibly inducing long-term cardiovascular changes. Furthermore, these findings highlight the importance of reducing arsenic exposure during pregnancy, and the need for more research on the impact of arsenic on maternal heart health and adverse pregnancy events.