Exposure to Airborne PM_2.5 Water-Soluble Inorganic Ions Induces a Wide Array of Reproductive Toxicity

Water-soluble inorganic ions (WSIIs, primarily NH₄⁺, SO₄^2-, and NO₃^-) 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 NH₄⁺, SO₄^2-, and NO₃^- 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 SO₄^2- exposure reduced the weight of testicle by 5.24% (p = 0.025); further, mice in the PM_2.5 SO₄^2- exposure group had 1.81 (p = 0.027) fewer offspring than the control group. PM_2.5 NH₄⁺, SO₄^2-, and NO₃^- 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.