Prenatal exposure to 33 endocrine-disrupting chemicals and pubertal development at age 9 in Spain

Puberty relies on a hormone-regulated cascade of events initiated in fetal life and might be disrupted by prenatal exposure to endocrine-disrupting chemicals (EDCs), with alterations manifesting during pubertal development. However, studies addressing prenatal exposure to multiple EDCs remain scarce. This study explores the associations between prenatal exposure to 33 EDCs and early sex maturation in 386 Spanish mother-child pairs (girls: 49%; recruitment: 2003-2005). We measured seven organochlorine compounds (OCs) and four perfluoroalkyl substances (PFAS) in maternal blood, and seven phenols and 15 phthalates in maternal urine. Pubertal development was assessed at age 9 using Tanner staging for genital development (GD), breast development (BD), and pubic hair development (PH) alongside salivary sex hormones. Sex-specific analyses included single-chemical (robust Poisson/linear regression) and mixture (principal components/Bayesian kernel machine regression) analyses. In single-chemical models, higher prenatal p,p'-DDE and p,p'-DDT concentrations were associated with delayed BD and GD, respectively, while PCB-180 and parabens (ETPA, BUPA) were associated with earlier BD, and phthalates were associated with earlier PH (girls: MEHP, MEHHP, MEOHP, and MECPP; boys: MEP and MnBP). For sex hormones, β-HCH (both sexes), p,p'-DDE, PCB-180, PFOS (boys), and p,p'-DDT, OH-MPHP (girls) were positively associated with testosterone, and HCB was positively associated with estradiol (boys). Conversely, BUPA, OH-MPHP (boys), and BPA (girls) were inversely associated with testosterone. In chemical mixture models, the first component of OCs was positively associated with male testosterone, but the results of other mixture analyses were unclear. Overall, prenatal exposure to some EDCs may impair fetal programming of puberty, yet the impact of chemical mixtures remains uncertain.