The aim of this application is to test the role of prenatal sex steroid hormones as the link between first trimester phthalate (synthetic endocrine disrupting chemical) exposure and newborn anogenital distance (AGD). Primary genitourinary development and programming occurs in the first 5-18 weeks of human gestation when the developing fetus is extremely sensitive to changes in sex steroid hormone concentrations that direct genital differentiation and development. AGD develops during this programming window and is a hormone sensitive reproductive toxicity endpoint commonly used in animal studies. Changes in AGD are associated with clinically significant newborn reproductive tract abnormalities and reduced fertility and abnormal semen parameters later in life. The general population is widely exposed to phthalates which can affect hormone concentrations and function during gestation leading to adverse hormone-mediated outcomes in animal and humans, including changes in AGD. The Prenatal Environmental Exposure and Reproductive Hormone Concentrations (PERCH) study will use data and samples from The Infant Development and the Environment Study to determine the relationship between phthalate exposures and sex steroid hormone concentrations in early pregnancy. It will also examine the relationship between early pregnancy sex steroid hormones and AGD in male and female infants. PERCH will be the first study to examine phthalate exposures during the fetal genitourinary programming window in relation to sex steroid hormone concentrations and newborn AGD. Results have important implications for understanding the biological pathway in which phthalates may impact reproductive development as well as for policy surrounding phthalate exposures in vulnerable populations.
The Prenatal Environmental Exposure and Reproductive Hormone Concentrations (PERCH) study will provide important information on the relationship between phthalate exposures in pregnancy and sex steroid hormone concentrations which play an important role in fetal genital development. We will also examine if sex steroid hormone concentrations during early pregnancy are related to infant anogenital distance, a reproductive toxicity endpoint. Results from this study will allow us to: 1) Understand a pathway by which phthalates may affect genital development and 2) Determine if hormone concentrations in early pregnancy could be early indicators of infant genital developmental outcomes at birth.
|Qian, J; Pentz, K; Zhu, Q et al. (2015) USP7 modulates UV-induced PCNA monoubiquitination by regulating DNA polymerase eta stability. Oncogene 34:4791-6|