Exposure to Airborne PM 2.5 Water-Soluble Inorganic Ions Induces a Wide Array of Reproductive Toxicity.

Water-soluble inorganic ions (WSIIs, primarily NH 4 + , SO 4 2- , and NO 3 - ) are major components in ambient PM 2.5 , but their reproductive toxicity remains largely unknown. An animal study was conducted where parental mice were exposed to PM 2.5 WSIIs or clean air during preconception and the gestational period. After delivery, all maternal and offspring mice lived in a clean air environment. We assessed reproductive organs, gestation outcome, birth weight, and growth trajectory of the offspring mice. In parallel, we collected birth weight and placenta transcriptome data from 150 mother-infant pairs from the Rhode Island Child Health Study. We found that PM 2.5 WSIIs induced a broad range of adverse reproductive outcomes in mice. PM 2.5 NH 4 + , SO 4 2- , and NO 3 - exposure reduced ovary weight by 24.22% (p = 0.005), 14.45% (p = 0.048), and 16.64% (p = 0.022) relative to the clean air controls. PM 2.5 SO 4 2- exposure reduced the weight of testicle by 5.24% (p = 0.025); further, mice in the PM 2.5 SO 4 2- exposure group had 1.81 (p = 0.027) fewer offspring than the control group. PM 2.5 NH 4 + , SO 4 2- , and NO 3 - exposure all led to lower birth than controls. In mice, 557 placenta genes were perturbed by exposure. Integrative analysis of mouse and human data suggested hypoxia response in placenta as an etiological mechanism underlying PM 2.5 WSII exposure's reproductive toxicity.