Maternal Exposure to Carbamazepine at Environmentally Relevant Concentrations Causes Growth Delay in Mouse Embryos.

Abstract

The anticonvulsant drug carbamazepine is ubiquitous in the environment and has even even detected in human urine after consuming produce irrigated with reclaimed wastewater. Whether unintentional carbamazepine exposure through food and water affects public health is unknown. Its potential adverse effects are particularly concerning during pregnancy, as carbamazepine increases the risk of intrauterine growth restriction and congenital malformations in fetuses of carbamazepine-prescribed mothers. While environmental carbamazepine levels are much lower than clinical doses, its impact on early embryonic development, a period highly susceptible to malformations, requires investigation. This study used mice to examine the effect of exposing female mice to environmentally relevant carbamazepine concentrations (200/500/2000 ng/L in their drinking water) on embryos at gestation day 9.5. While no obvious malformations or compromised survival rates were observed, embryonic growth was delayed in a dose-dependent manner; developmental stages were younger than expected, fewer somites had formed, and heart maturation was delayed. Molecular analysis revealed a reduced expression of key developmental genes and decreased proliferation, linking growth delay to perturbed mechanisms. This study is the first to link maternal exposure to environmentally relevant carbamazepine concentrations with growth delay in mammalian embryos. Given that prenatal growth restriction contributes to human morbidity, this finding calls for further risk analyses of environmental pharmaceuticals on fetal health.