Fine particulate matter (PM₂.₅) is believed to be one of the most hazardous air pollution with a ubiquitous presence. Animal studies have reported the association between prenatal exposure to traffic pollutant (not exclusively including PM₂.₅) and reproductive development in male offspring. However, the effects of prenatal exposure to PM₂.₅ on reproductive health in children are still unknown. The present study was based on the Shanghai-Minhang Birth Cohort Study (S-MBCS). A total of 876 pregnant women and their infants were included. Infants’ anogenital distance (AGD, the distance from the anus to the genitals; AGDap [anus-penis] and AGDas [anus-scrotum] for boys, and AGDac [anus-clitoris] and AGDaf [anus-fourchette] for girls) were measured at birth. PM₂.₅ concentrations during pregnancy were estimated using satellite based modeling approach. Multiple linear regression analysis and multiple informant model were conducted to examine the associations between prenatal exposure to PM₂.₅ (pre μg/m³) and offspring’s AGDs (mm). In order to minimize the misclassification of exposure, a sensitivity analysis restricted to mothers being off work during pregnancy was performed. In multiple linear regression models, we found that prenatal exposure to PM₂.₅ during the 1ˢᵗ and 3ʳᵈ trimesters was associated with shorter AGDs. In multiple informant model, similar patterns were found, and statistically significant reductions were observed in AGDap (β=−0.278, 95%CI: -0.343∼-0.212), AGDac (β=−0.188, 95%CI: -0.247∼-0.130) and AGDaf (β= −0.163, 95%CI: -0.238∼-0.088) with PM₂.₅ exposure during the 1ˢᵗ trimester, and AGDap (β=−0.201, 95%CI: -0.247∼-0.155), AGDas (β=−0.158, 95%CI: -0.198∼-0.117), AGDac (β=−0.128, 95%CI: -0.167∼-0.089) and AGDaf (β = −0.144, 95%CI: -0.194∼-0.094) with PM₂.₅ exposure during the 3ʳᵈ trimester. The sensitivity analysis restricted to women being off work during pregnancy showed similar results. PM₂.₅ exposure during the 1ˢᵗ and 3ʳᵈ trimesters was associated with shortened AGDs in offspring at birth. Our findings provide preliminary evidence that prenatal exposure to PM₂.₅ might be associated with the reproductive development of offspring.

Anogenital distance (AGD), a useful anthropometric measurement for genital development in both animals and humans, was originally found by reproductive toxicologists in rodent experiments. As an easy-to-measure and sensitive marker, AGD has become a bioassay of fetal androgen action and a well-established reproductive toxicity endpoint in animals. It is generally accepted that AGD is sexually dimorphic in many mammals, with males having longer AGD than females. Exposure to proposed endocrine disruptors may result in reduced AGD; thus, it has been used to measure health effects of compounds with endocrine-altering properties or endocrine-disrupting chemicals (EDCs) in environmental toxicology. Moreover, AGD is an important clinical measure to address endocrine-sensitive endpoints in the first year of life and to assess the adverse impact of in utero exposure to environmental EDCs. Recently, AGD has been identified as one of the endpoints in the US Environmental Protection Agency guidelines for reproductive toxicity studies in humans, but use of AGD in human studies is still rare, and the results remain mixed and inconclusive due to many reasons. In order to achieve a breakthrough, researchers are endeavoring to standardize the measurement of AGD, normalize age-specific population data in different ethnic groups, and conduct more in-depth human researches in this field.