Arsenic and the placenta: A review with emphasis on the immune system

Chronic arsenic exposure affects over 140 million people globally. While arsenic easily crosses the placenta, the specific mechanisms impacting placental immune cell populations and fetal health are unclear. Maternal arsenic exposure is epidemiologically linked to increased infection risk, mortality, and cancer susceptibility in offspring, emphasizing the importance of understanding placentally-mediated immune effects. This review explores the potential role of the placenta, a key organ for immune transfer to the developing fetus, in mediating chronic low-dose arsenic exposure effects. Examining three potential pathways-direct contaminant transfer, altered immune transfer from the mother, and indirect impact on fetal immune programming via maternal and placental signaling-the review highlights studies associating maternal arsenic levels with immune-related outcomes, including changes in cord blood T cell populations and increased placental inflammation. Placental gene expression analysis reveals alterations in pathways related to oxidative stress, proteasome activity, and aquaglyceroporin transporter expression. Impact on placental DNA methylation and microRNA regulation as well as on trophoblast dysfunction is discussed, with evidence suggesting inhibited trophoblast migration and placental growth factor expression. The complexity of mixtures, nutrition, and environmental interactions add challenges to investigating the placenta's role in immune programming. Despite inconsistent findings on placental morphology alterations, evidence suggests a potential link between arsenic exposure, placental anomalies, and adverse birth outcomes. Further research is crucial to comprehend the effects of prenatal arsenic exposure on trophoblasts, placental immune cells, and subsequent long-term consequences for fetal immune development and birth outcomes.