Prenatal exposure to PM_2.5 led to impaired respiratory function in adult mice

PM_2.5 is a complex mixture, with water-soluble inorganic ions (WSII), mainly NH₄⁺, SO₄^2-, and NO₃^-, constituting major components. Early-life PM_2.5 exposure has been shown to induce adverse health consequence but it is difficult to determine whether such an effect occurs prenatally (preconception, gestational) or postnatally in human studies.

Four groups of C57BL/6 J mice were assigned to four exposure conditions: PM_2.5 NO₃^-, PM_2.5 SO₄^2-, PM_2.5 NH₄⁺ and clean air, and exposure started at 4 weeks old. At 8 weeks old, mice bred within group. The exposure continued during gestation. After delivery, both the maternal and F₁ mice (offspring) were kept in clean air without exposure to PM_2.5. Respiratory function and pulmonary pathology were assessed in offspring mice at 8 weeks of age. In parallel, placenta tissue was collected for transcriptome profiling and mechanistic investigation.

F₁ mice in PM_2.5 NH₄⁺, SO₄^2- and NO₃^- groups had 32.2 % (p=6.0e-10), 30.3 % (p=3.8e-10) and 16.9 % (p=5.7e-8) lower peak expiratory flow (PEF) than the clean air group. Importantly, the exposure-induced lung function decline was greater in male than female offspring. Moreover, exposure to PM_2.5 WSII before conception and during gestation was linked to increased airway wall thickness and elevated pulmonary neutrophil and macrophage counts in the offspring mice. At the molecular level, the exposure significantly disrupted gene expression in the placenta, affecting crucial functional pathways related to sex hormone response and inflammation.

PM_2.5 WSII exposure during preconception and gestational period alone without post-natal exposure substantially impacted offspring's respiratory function as measured at adolescent age. Our results support the paradigm of fetal origin of environmentally associated chronic lung disease and highlight sex differences in susceptibility to air pollution exposure.