Phthalates are high volume multifunctional chemicals used to manufacture and formulate many consumer and commercial products. Their ubiquitous use has led to widespread exposure of both the working and general population. There is toxicological data from studies in experimental animals showing that some phthalates are reproductive and developmental toxins. Toxicological studies have found associations of dibutyl phthalate, di-(2-ethylhexyl) phthalate, and butylbenzyl phthalate with decreased fertility and embryo implantation rates, altered embryo/fetal development, and increased embryo/fetal loss. Despite the high volume use of phthalates and the consistent evidence from experimental animals on their reproductive toxicity, there is limited human data on the potential adverse effects of phthalates on reproductive and development health. Therefore, the proposed study was undertaken to explore the relationship between maternal occupational and environmental exposure to phthalates and reproductive and developmental toxicity. The proposed study will use data and biological specimens collected from women in our ongoing NIEHS funded reproductive health study. In the NIEHS study, infertile couples referred to the Massachusetts General Hospital for in vitro fertilization (IVF) are recruited. From both the male and female partner, we collect questionnaire data and biological specimens. The NIEHS study focuses on the relationship of phthalate exposure with clinical and intermediate measure of male fertility. The proposed study will focus on maternal exposure to phthalates. IVF will be used as a model system to assess the early stages of development. Reproductive and developmental endpoints that will be measured include oocyte production, oocyte fertilization, embryo implantation, and embryo development. Failure at these developmental endpoints may result in infertility, as well as pregnancy loss. Additional endpoints include pregnancy and live birth rates, as well as measures of fetal growth. Maternal occupational exposure will be assessed with a detailed occupational history questionnaire and urinary biomarkers will be used to measure phthalate exposure. The proposed study is innovative since it will use IVF as a model system for studying early embryo and fetal development, previously unobservable. Since occupational and environmental exposure to phthalates is widespread, detecting even small adverse effects will have large public health significance.
