Grant Number:
Principal Investigator:
Sathyanarayana, Sheela
Institution:
Seattle Children's Hospital
Most Recent Award Year:
2011
Lifestage of Participants:
Exposure:
Prenatal; Adulthood (mother)
Assessment:
Infant (0-1 year)
Exposures:
Personal Care/Consumer Products:
Phthalates
Health Outcomes:
Birth Outcomes:
Reproductive tract malformations (anogenital distance, ano-scrotal distance, penile width)
Biological Sample:
Saliva/buccal cells; Urine (mother)
Other Participant Data:
Genotyping data
Genes or Other DNA Products Studied:
Genes involved in male genital development (e.g., AR, ESR1, ESR2, SRD5A2, ATF3, INSL3/LGR8, CTGF, CYR61)
Abstract:
In specific areas of industrialized nations, the rising incidence of hypospadias and cryptorchidism from 1950- 2000 parallels the production and use of some phthalates, anti-androgenic synthetic chemicals used as plasticizers, that have been found in the urine of over 90% of the general population in the United States. Genetic and environmental factors play a role in the development of abnormal development of male reproductive outcomes. Polymorphisms in several genes including AR, SRD5A2, INSL3/LGR8, ESR1, ESR2, ATF3, CTGF, and CYR61 are associated with adverse male reproductive development. Prenatal exposure to phthalates leads to hypospadias, cryptorchidism, and shortened anogenital distance (AGD) and smaller penile width (PW) in animal studies. Our hypothesis is that single nucleotide and repeat polymorphisms in genes involved in hormone mediated male genital development are associated with shortened AGD and ano-scrotal distance (ASD: a similar measure to AGD in animals) and smaller PW; and this relationship is modified by prenatal phthalate exposure. To address this hypothesis, the proposed GEAR (Genetics and the Environment Associated with Male Reproduction) study will genotype candidate genes and repeat polymorphism length in 400 male infants recruited into a prospective NIEHS-funded cohort study, TIDES (The Infant Development and Environment Study), and in whom AGD, ASD, and PW and maternal pregnancy urinary phthalate concentrations are being measured. We will obtain and genotype buccal swab/FTA card DNA samples from infants during already scheduled birth exams in TIDES. We will first examine the association between genetic variation in AR, ESR1, ESR2, SRD5A2, ATF3, INSL3/LGR8, CTGF, CYR61 and shortened AGD and ASD, and smaller PW; then proceed to test whether this association is modified by first trimester urine phthalate exposures. By taking advantage of a prospective parent study design, GEAR is cost effective and novel by allowing for assessment of genetic variation and phthalate exposures in male reproductive development. If a relationship exists between genetic polymorphisms associated with male reproductive abnormalities, phthalate exposure, and novel clinical phenotypes AGD, ASD, and PW, these findings would: 1) enhance understanding of the relationship between genotype and novel clinical phenotypes of early male genital development, and 2) be among the first studies to examine gene/phthalate interactions in male reproductive development, and 3) contribute to future research that uses genotype, environmental exposure, and phenotype to predict future male reproductive health.
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Related NIEHS-Funded Study Populations
The Infant Development and Environment Study (TIDES)
Principal Investigator:
Swan, Shanna
| Study Population Page Study Population c109
Institution:
Icahn School of Medicine at Mount Sinai
Location:
San Francisco, California; Minneapolis, Minnesota; Rochester, New York; Seattle, Washington
Number of Participants::
1,000 Mothers and 758 Children
Brief Description::
This is a multi-site pregnancy study examining how the mother’s exposure to everyday chemicals while pregnant may affect the developing fetus. The study recruited approximately 1,000 pregnant women in 2010-2012 and examined 758 children at birth.