Veretnik Eliane, Douek-Maba Orit, Kalev-Altman Rotem, Haiman Aluma, Quint Maxim, Mordehay Vered, Shlezinger Neta, Cinnamon Yuval, Chefetz Benny, Sela-Donenfeld Dalit
Koret School of Veterinary Medicine, The RH Smith Faculty of Agriculture, Food and Environmental Sciences, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
Department of Soil and Water Sciences, The RH Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 7610001, Israel.
ACS Omega. 2025 Aug 14;10(33):37687-37701. doi: 10.1021/acsomega.5c04235. eCollection 2025 Aug 26.
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.
抗惊厥药物卡马西平在环境中普遍存在，甚至在食用经再生废水灌溉的农产品后，人体尿液中也检测到了卡马西平。通过食物和水无意接触卡马西平是否会影响公众健康尚不清楚。其潜在的不良影响在孕期尤其令人担忧，因为卡马西平会增加服用卡马西平的母亲所怀胎儿出现宫内生长受限和先天性畸形的风险。虽然环境中的卡马西平水平远低于临床剂量，但其对极易出现畸形的早期胚胎发育的影响仍需进行研究。本研究利用小鼠来检测在妊娠第9.5天，将雌性小鼠暴露于环境相关浓度的卡马西平（饮用水中浓度为200/500/2000纳克/升）对胚胎的影响。虽然未观察到明显的畸形或存活率降低的情况，但胚胎生长出现了剂量依赖性延迟；发育阶段比预期的要早，形成的体节较少，心脏成熟也延迟了。分子分析显示关键发育基因的表达减少，细胞增殖降低，这将生长延迟与机制紊乱联系了起来。本研究首次将母体暴露于环境相关浓度的卡马西平与哺乳动物胚胎的生长延迟联系起来。鉴于产前生长受限会导致人类发病，这一发现呼吁对环境中的药物对胎儿健康进行进一步的风险分析。
