Associations ofExposuretoAirPollutionduringtheMaleProgrammingWindow and Mini-PubertywithAnogenitalDistanceandPenileWidthatBirthandat1 Year ofAgeintheMulticenterUS TIDESCohort

BACKGROUND: Ambient airpollutionmaybeadevelopmentalendocrinedisruptor. Inanimalmodels, gestationalandperinatalexposuretodiesel exhaust andconcentratedparticulatematteraltersanogenitaldistance(AGD), amarkerofprenatalandrogenactivity, inbothsexes. Littleisknown in humans. OBJECTIVES: We examinedexposureto fine particulatematter(PM2:5) andnitrogendioxide(NO2) inrelationtohumanAGDatbirthandat1yearof age, focusingonexposuresduringcriticalwindowsofreproductivedevelopment: themaleprogrammingwindow(MPW; gestationalweeks8-14) and mini-puberty(postnatalmonths1-3). METHODS: The InfantDevelopmentandEnvironmentStudy(TIDES) recruited first trimesterpregnantwomen(n= 687) atfourU.S. sites (Minneapolis, Minnesota; Rochester, NewYork; SanFrancisco, California; andSeattle, Washington) from2010to2012. Wemeasuredanustoclitoris (AGD-AC) andanustofourchette(AGD-AF) infemaleinfantsatbirth; inmales, wemeasuredanustopenis(AGD-AP), anustoscrotum(AGDAS), andpenilewidthatbirthandat1yearofage. Usingadvancedspatiotemporalmodels, weestimatedmaternalexposure to PM2:5 and NO2 in the MPW andmini-puberty. Covariate-adjusted, sex-stratified linearregressionmodelsexaminedassociationsbetweenPM(2:5) and NO2 and AGD. RESULTS: In males, a1-lg=m(3) increase in PM2:5 exposure during the MPW was associated with shorter AGD at birth, but a longer A GD at 1year of age (e.g., birthAGD-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 PM2:5 exposure was also associated with shorter maleAGD-AP(b= - 0:50 mm; 95% CI: -0:89, -0:11) at1 year of age. Althoughnotassociatedwith male AGD measures, 1-ppbincreases in NO2 exposure during the MPW (b= - 0:07 mm; 95% CI: -0:02, -0:12) andmini-puberty(b= - 0:04 mm; 95% CI: -0:08, 0.01) werebothassociatedwithsmallerpenilewidthat1yearofage. Results were similar in multipollutant models, where weal so observed that in females AGD-ACwasinverselyassociated with PM2:5 exposure, but positivelyas sociated with NO2 exposure. DISCUSSION: PM2:5 and NO2 exposures duringcriticalpre- and post natal windows may disruptreproductive development. More work is needed to confirm these novel results and c larify mechanisms. https://doi.org/10.1289/EHP12627