Associations of Exposure to Air Pollution during the Male Programming Window and Mini-Puberty with Anogenital Distance and Penile Width at Birth and at 1 Year of Age in the Multicenter U.S. TIDES Cohort

BACKGROUND: Ambient air pollution may be a developmental endocrine disruptor. In animal models, gestational and perinatal exposure to diesel exhaust and concentrated particulate matter alters anogenital distance (AGD), a marker of prenatal androgen activity, in both sexes. Little is known in humans. OBJECTIVES: We examined exposure to fine particulate matter (PM_2:5) and nitrogen dioxide (NO₂) in relation to human AGD at birth and at 1 year of age, focusing on exposures during critical windows of reproductive development: the male programming window (MPW; gestational weeks 8–14) and mini-puberty (postnatal months 1–3). METHODS: The Infant Development and Environment Study (TIDES) recruited first trimester pregnant women (n = 687) at four U.S. sites (Minneapolis, Minnesota; Rochester, New York; San Francisco, California; and Seattle, Washington) from 2010 to 2012. We measured anus to clitoris (AGD-AC) and anus to fourchette (AGD-AF) in female infants at birth; in males, we measured anus to penis (AGD-AP), anus to scrotum (AGD-AS), and penile width at birth and at 1 year of age. Using advanced spatiotemporal models, we estimated maternal exposure to PM_2:5 and NO₂ in the MPW and mini-puberty. Covariate-adjusted, sex-stratified linear regression models examined associations between PM_2:5 and NO₂ and AGD. RESULTS: In males, a 1-lg=m³ increase in PM_2:5 exposure during the MPW was associated with shorter AGD at birth, but a longer AGD at 1 year of age (e.g., birth AGD-AP: b = − 0:35 mm; 95% CI: −0:62, −0:07; AGD-AS: b = 0:37 mm; 95% CI: 0.02, 0.73). Mini-pubertal PM_2:5 exposure was also associated with shorter male AGD-AP (b = − 0:50 mm; 95% CI: −0:89, −0:11) at 1 year of age. Although not associated with male AGD measures, 1-ppb increases in NO₂ exposure during the MPW (b = − 0:07 mm; 95% CI: −0:02, −0:12) and mini-puberty (b = − 0:04 mm; 95% CI: −0:08, 0.01) were both associated with smaller penile width at 1 year of age. Results were similar in multipollutant models, where we also observed that in females AGD-AC was inversely associated with PM_2:5 exposure, but positively associated with NO₂ exposure. DISCUSSION: PM_2:5 and NO₂ exposures during critical pre-and postnatal windows may disrupt reproductive development. More work is needed to confirm these novel results and clarify mechanisms. https://doi.org/10.1289/EHP12627.