Dioxins and Male Pubertal Growth and Development

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DESCRIPTION (provided by applicant): Puberty is the dynamic physical, behavioral, and hormonal transition from the pre-pubertal state to sexual maturity and adult reproductive capacity. Temporal trends towards an earlier onset of puberty have been reported particularly for girls with limited data available for boys. Although risk factors have not been clearly identified for this reported change in the age of female pubertal onset, the effects of environmental chemicals and that of over nutrition and obesity on the reproductive axis have both been implicated as potential factors. In boys, there are limited longitudinal cohort studies on the timing and progression of puberty and few studies on the impact of environmental chemicals. Environmental chemicals of particular concern for altered age of onset and progression of male puberty include chlorinated aromatic hydrocarbons, a family of highly toxic environmental contaminants that includes polychlorinated dibenzo-p- dioxins, polychlorinated dibenzofurans and polychlorinated biphenyls (PCBs), and heavy metals, specifically lead. In laboratory animals and limited human studies, dioxins, furans, PCBs and lead were shown to alter pubertal development and growth and affect adult testicular function. In this competing continuation application, we propose to prospectively extend follow-up of our cohort of 499 Russian boys through puberty and into adulthood. The boys reside in Chapaevsk, Russia, an industrial town that has documented high exposure to dioxins, furans, PCBs and lead. The specific aims are to investigate the relationship of peri-pubertal serum concentrations of dioxins, furans, PCBs and lead with: 1) progression of male pubertal development and age at attainment of sexual maturation (measured by testicular volume and Tanner stages); 2) somatic growth, specifically height, height velocity, weight gain, and BMI; 3) altered serum concentrations of hormones that regulate somatic growth and pubertal development (testosterone, inhibin- B, MIS, LH, FSH, IGF-1, IGF-BP3, TSH and free T4); 4) altered adult testis function, specifically semen quality and hormonal markers of mature testis function and the reproductive axis (testosterone, inhibin-B, LH and FSH). The proposed study is innovative because it represents one of the few large prospective cohort studies on the impact of the environment on male pubertal development, growth and reproductive function. Alterations in the timing of puberty and in growth have been shown to have adverse public health and clinical implications. For instance, altered pubertal timing adversely impacts physical and sexual maturation, social, cognitive and behavioral development in adolescence, and subsequent risk of adult obesity and metabolic disorders. Furthermore, exposure to environmental chemicals during the sensitive window of male pubertal development may adversely impact fertility and the next generation through paternally mediated effects. Therefore, the identification of potentially remediable risk factors such as exposure to dioxins, furans, PCBs and lead, is critical to both advancing our understanding of the impact of the environment on child health and protecting both child health and subsequent generations.