A temporal trend towards an earlier age of onset of puberty has been reported in both girls and boys. Although specific etiologies have not been clearly identified for this reported change in the age of pubertal onset, the effects of environmental chemicals as well as that of overnutrition and obesity on the reproductive axis have both been implicated as potential factors. Environmental chemicals of concern are a family of compounds that includes polychlorinated dibenzo-p-dioxins, dibenzofurans and polychlorinated biphenyls. These compounds are reproductive and developmental toxins in laboratory animals and in limited human studies. In the proposed application, we target a population in Chapaevsk, Russia, an industrial town that has high documented environmental levels of dioxins and PCBs. We propose to prospectively extend follow-up of our cohort of 550 eight- to nine-year old boys, in which we are investigating the association of dioxins and PCBs with: 1) the timing and tempo of pubertal development;2) linear growth, weight gain, body composition (per cent body fat), and body mass index;and 3) biochemical changes in hormones that regulate growth and pubertal development. At recruitment, baseline examinations are performed that include physical and physiologic markers of growth and pubertal development. Physical markers include anthropomorphic measurements and determination of pubertal maturation by Tanner staging for genital and pubic hair development and assessment of testicular volume. Physiological markers consist of biochemical measures of the hypothalamic-pituitary-gonadal axis, assessed by serum gonadotropins (follicle-stimulating hormone and luteinizing hormone), sex steroids, inhibin-B and Mullerian inhibiting substance, as well as hormones that regulate somatic growth and metabolism, such as thyroxine, thyroid stimulating hormone, leptin, and insulin- like growth factor-1. Blood samples are collected from the boys and their mothers for dioxin and PCB analysis. Chemicals that alter growth and pubertal development have significant clinical and public health implications for both childhood and adult health. Specific implications of altered growth and development include impaired fertility, increased risk of obesity, and risk of behavioral and psychological disorders. The proposed study is unique since it will represent one of the first large longitudinal studies to explore the relationship of dioxins and PCBs with growth and development in pre-pubertal boys.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES014370-05
Application #
7763800
Study Section
Special Emphasis Panel (ZRG1-HOP-Q (90))
Program Officer
Gray, Kimberly A
Project Start
2006-04-13
Project End
2011-01-31
Budget Start
2010-02-01
Budget End
2011-01-31
Support Year
5
Fiscal Year
2010
Total Cost
$531,062
Indirect Cost
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
Greenspan, Louise C; Lee, Mary M (2018) Endocrine disrupters and pubertal timing. Curr Opin Endocrinol Diabetes Obes 25:49-54
Pilsner, J Richard; Shershebnev, Alex; Medvedeva, Yulia A et al. (2018) Peripubertal serum dioxin concentrations and subsequent sperm methylome profiles of young Russian adults. Reprod Toxicol 78:40-49
Burns, Jane S; Williams, Paige L; Lee, Mary M et al. (2017) Peripubertal blood lead levels and growth among Russian boys. Environ Int 106:53-59
Mínguez-Alarcón, Lidia; Sergeyev, Oleg; Burns, Jane S et al. (2017) A Longitudinal Study of Peripubertal Serum Organochlorine Concentrations and Semen Parameters in Young Men: The Russian Children's Study. Environ Health Perspect 125:460-466
Sergeyev, Oleg; Burns, Jane S; Williams, Paige L et al. (2017) The association of peripubertal serum concentrations of organochlorine chemicals and blood lead with growth and pubertal development in a longitudinal cohort of boys: a review of published results from the Russian Children's Study. Rev Environ Health 32:83-92
Burns, Jane S; Lee, Mary M; Williams, Paige L et al. (2016) Associations of Peripubertal Serum Dioxin and Polychlorinated Biphenyl Concentrations with Pubertal Timing among Russian Boys. Environ Health Perspect 124:1801-1807
Lam, Thuy; Williams, Paige L; Lee, Mary M et al. (2015) Prepubertal Serum Concentrations of Organochlorine Pesticides and Age at Sexual Maturity in Russian Boys. Environ Health Perspect 123:1216-21
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
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
Cantonwine, David E; Hauser, Russ; Meeker, John D (2013) Bisphenol A and Human Reproductive Health. Expert Rev Obstet Gynecol 8:

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