Cross-Generational Impact of Maternal Exposure to Low Level of PM2.5 on Kidney Health

Am J Nephrol. 2024 Nov 21:1-14. doi: 10.1159/000542135. Online ahead of print.

Abstract

Introduction: Inhaled fine and ultrafine particulate matter may affect organs other than the lung, including the kidney. Recent studies have consistently shown the possibility of air pollution in highly polluted countries to be nephrotoxic. However, in countries like Australia, where air quality generally adheres to or remains below the WHO standards, the subtle yet consequential impacts of chronic exposure to seemingly safe levels of traffic PM2.5, are a subject of increasing significance. However, how such exposures in the peri-pregnancy period affect kidney health in mothers and the offspring is unclear, which formed the aims of this study.

Methods: Female Balb/c mice were exposed to PM2.5 (5 μg/day) delivered nasally for 6 weeks prior to mating, during gestation and lactation (PM group). In a subgroup, PM2.5 was switched to saline from mating until offspring were weaned to model mothers moving to areas with clean air. Kidneys were analysed in dams and adult offspring at 13 weeks of age.

Results: PM2.5 induced oxidative stress without histological changes in the dam's kidney. However, male PM offspring displayed in utero underdevelopment, characterised by reduced body weight and kidney-to-body weight at birth compared to control offspring, and lower glomerular numbers, with a marked increase in albuminuria, glomerulosclerosis, inflammation, oxidative stress, and mitochondrial injury. Female PM offspring had delayed postnatal development, lower glomerular numbers, increased glomerulosclerosis, and oxidative stress injury markers. Removal of PM2.5 from conception significantly reduced DNA oxidation and kidney damage in the offspring.

Conclusion: There is no safe level of ambient PM2.5 for kidney health when exposed in utero. Maternal PM2.5 exposure equally impacts the kidney health of male and female offspring. Removal of PM2.5 from conception was overall protective to the offspring.

Keywords: CKD; Foetal programming; Mitochondria; Oxidative stress; Traffic-derived particulate matter.