The influence of endocrine disruptors on male pubertal timing

Abstract

Wildlife observations and toxicological studies in animals have revealed that endocrine disruptors have adverse effects on reproductive health, including altering the timing of pubertal development in both males and females. In contrast to the early puberty observed with EDC exposure in females, most antiandrogenic and estrogenic compounds cause a delay in male pubertal onset accompanied by dysfunction of testicular steroidogenic pathways and perturbation in secondary sexual maturation. Animal studies have identified critical windows of vulnerability for susceptibility that vary among compounds. For several estrogenic compounds such as DES and DDE, the juvenile and peripubertal windows are key exposure periods for the outcome of preputial separation, a hallmark of pubertal onset in male rodents. Gestational and neonatal exposures have been shown to have no impact on pubertal timing. Conversely, gestational exposures to PCBs, dioxins, and flutamide (an antiandrogen) delay pubertal onset. A small but growing number of epidemiologic studies have shown that EDCs can also alter pubertal timing and progression in humans. Recent studies demonstrate an association of lead, dioxins, endosulfan, and PCBs on delaying onset of puberty and age of attaining pubertal milestones and a weaker association of serum organochlorines with earlier puberty. Cumulatively, these studies have identified key factors that affect vulnerability and toxicity. Dose, duration, and timing of exposure, genetic susceptibility, and the endogenous endocrine milieu may all modulate the effects of exposures to EDCs. Human studies are further complicated by the long interval between exposure and outcome and the likelihood of mixed exposures which may have opposing, additive, or synergistic actions on the reproductive system. In conclusion, animal and human data confirm perturbations in pubertal onset and attainment of late pubertal stages with early-life exposures to EDCs.