Early Life rDNA Copy-Number Variation and Ambient Particulate Matter Exposure: A Longitudinal Birth Cohort Study

Abstract In utero air pollution is a critical risk factor linked with adverse birth outcomes. Genomic alterations induced by air pollution can be precursors for the development of later-life diseases. Ribosomal DNA (rDNA) has an important role in genome stability and forms a potentially sensitive target for environmental stressors. Therefore, we studied the association between early life rDNA dynamics and prenatal and early childhood air pollution exposure. In the ENVIRONAGE birth cohort, we assessed rDNA copy number (rDNAcn) at birth and longitudinally after a mean follow-up of 4.5 years (5th–95th percentile: 4.1–5.3) using droplet digital PCR (ddPCR). Prenatal and postnatal exposures to particulate matter (PM10 and PM2.5) were estimated based on the maternal and child residential address. Distributed lag models (DLM) were applied to associate newborn rDNAcn, rDNAcn in childhood, and the longitudinal change in rDNAcn with prenatal air pollution exposures, accounting for potential confounders and covariates. A total of 171 newborns, including 84 girls (49.1%) with a mean gestational age of 39.1 weeks, had an rDNAcn of 245 (SD: 58.1) copies. After 4–6 years, the mean rDNAcn was 231 (SD: 55.7) copies. DLMs revealed sensitive windows of prenatal PM exposures during pregnancy for an inverse association with both rDNAcn at birth and in childhood, but not with the longitudinal change in rDNAcn. Newborn rDNAcn was inversely associated with PM exposure during the last trimester, with an SD-higher level in prenatal PM2.5 associated with −34.8 (95% CI: −60.0 to −9.7) lower newborn rDNAcn. In addition, an SD increment in prenatal PM2.5 during the entire pregnancy, first trimester, and last trimester was associated with −71.2 (95% CI: −117.0 to −25.3), −26.0 (95% CI: −46.3 to −5.7), and −33.0 (95% CI: −54.3 to −11.8) lower rDNAcn in childhood, respectively. Similar associations were observed for PM10. Finally, postnatal exposures were not associated with rDNAcn in childhood. Our findings show that prenatal particulate matter exposure is associated with a lower rDNAcn of newborns and that this association persists from birth to childhood. Therefore, early genomic effects on the level of rDNA that track over early child development are influenced by prenatal air pollution exposure. The long-term consequences of rDNA alterations in early life need to be elucidated in further follow-up studies.