The pubertal transition from pre-puberty to sexual maturity entails dynamic physical, behavioral, and hormonal changes. Although studies report temporal trends towards an earlier onset of puberty in girls, there are limited data in boys on temporal trends of pubertal onset. Moreover, there is a dearth of longitudinal studies on the impact of environmental chemicals on male puberty. Phthalates are one class of chemicals for which there is scientific and regulatory concern regarding their potential effects on male pubertal development and testicular function. This concern is based upon numerous experimental studies in rodents showing that some phthalates are anti-androgenic and are male developmental and reproductive toxicants, causing delayed pubertal onset, decreased serum testosterone concentrations and impaired semen quality. Based on the experimental data and the documented widespread human exposure to phthalates, in this competing renewal we propose to investigate the effect of phthalates (individual phthalates and their mixtures) on male pubertal development, reproductive hormones and semen quality. We will leverage our unique well-defined longitudinal cohort study of 499 Russian boys followed from enrollment at age 8 until 21 years. Our pilot data on a small subset of the cohort shows high urinary concentrations of multiple anti-androgenic phthalate metabolites. In the competing renewal, we will measure urinary concentrations of phthalate metabolites in archived urine samples collected annually during twelve years of follow-up. To evaluate the effect of phthalate exposure during three sensitive windows, we will pool annual urine samples for each boy as follows: 1) pre-pubertal window (pool all samples collected at annual visits when testicular volume <4 ml), 2) early through mid-pubertal window (pool all samples collected at annual visits when testicular volume is between 4 and less than 15 ml), and 3) late-pubertal window (pool all samples collected at annual visits when testicular volume is 15 ml or greater). Our study will be one of the first prospective cohort studies in boys that will assess the effect of phthalate exposure at three sensitive windows on puberty and semen quality. We also have the unique opportunity to investigate the effect of exposure to real-life mixtures of phthalates and environmental chemicals/metals (organochlorines, including dioxins, furans, PCBs, pesticides and lead were measured in our current funding period) on puberty and semen quality. Altered timing and progression of puberty are an important public health issue because they may have adverse effects on growth, social functioning, cognitive and behavioral development, and adult metabolic and reproductive health. Furthermore, poor semen quality increases risk of infertility. In conclusion, elucidating the association of prevalent environmental chemicals with adverse male reproductive development may reveal potentially modifiable risk factors (for example, reducing phthalate use in consumer products).

Public Health Relevance

The pubertal transition from pre-puberty to sexual maturity entails dynamic physical, behavioral, and hormonal changes. The proposed project will investigate environmental risk factors, including exposure to phthalates, for altered pubertal development. 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 #
5R01ES014370-12
Application #
9445458
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Boyles, Abee
Project Start
2006-04-13
Project End
2021-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
12
Fiscal Year
2018
Total Cost
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
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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