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.

Public Health Relevance

The proposed project will determine environmental risk factors for altered growth and pubertal development in boys. In addition, when the boys reach adulthood, environmental risk factors for altered semen quality will also be explored.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES014370-07
Application #
8217168
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Gray, Kimberly A
Project Start
2006-04-13
Project End
2015-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
7
Fiscal Year
2012
Total Cost
$508,287
Indirect Cost
$101,556
Name
Harvard University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
Burns, Jane S; Williams, Paige L; Korrick, Susan A et al. (2014) Association between chlorinated pesticides in the serum of prepubertal Russian boys and longitudinal biomarkers of metabolic function. Am J Epidemiol 180:909-19
Lam, Thuy; Williams, Paige L; Lee, Mary M et al. (2014) Prepubertal organochlorine pesticide concentrations and age of pubertal onset among Russian boys. Environ Int 73:135-42
Humblet, Olivier; Korrick, Susan A; Williams, Paige L et al. (2013) Genetic modification of the association between peripubertal dioxin exposure and pubertal onset in a cohort of Russian boys. Environ Health Perspect 121:111-7
Cantonwine, David E; Hauser, Russ; Meeker, John D (2013) Bisphenol A and Human Reproductive Health. Expert Rev Obstet Gynecol 8:
Fleisch, Abby F; Burns, Jane S; Williams, Paige L et al. (2013) Blood lead levels and serum insulin-like growth factor 1 concentrations in peripubertal boys. Environ Health Perspect 121:854-8
Burns, Jane S; Williams, Paige L; Sergeyev, Oleg et al. (2012) Serum concentrations of organochlorine pesticides and growth among Russian boys. Environ Health Perspect 120:303-8
Korrick, Susan A; Lee, Mary M; Williams, Paige L et al. (2011) Dioxin exposure and age of pubertal onset among Russian boys. Environ Health Perspect 119:1339-44
Burns, Jane S; Williams, Paige L; Sergeyev, Oleg et al. (2011) Serum dioxins and polychlorinated biphenyls are associated with growth among Russian boys. Pediatrics 127:e59-68
Humblet, Olivier; Sergeyev, Oleg; Altshul, Larisa et al. (2011) Temporal trends in serum concentrations of polychlorinated dioxins, furans, and PCBs among adult women living in Chapaevsk, Russia: a longitudinal study from 2000 to 2009. Environ Health 10:62
Humblet, Olivier; Williams, Paige L; Korrick, Susan A et al. (2011) Dioxin and polychlorinated biphenyl concentrations in mother's serum and the timing of pubertal onset in sons. Epidemiology 22:827-35

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