Organics Core: Organics and Reproductive Health
Organics and Reproductive Health: Following pilot funding from the Center, Dr. Hauser received an R01 grant from the National Institute of Environmental Health Sciences to conduct a large epidemiologic study on environmental challenges to reproductive health and development. In collaboration with Dr. Ryan, they published the first human studies on the association between phthalates and male reproductive health (Duty, Silva et al. 2003; Duty, Singh et al. 2003). Urinary phthalate concentration, semen quality, and a novel measure of sperm DNA integrity, using the neutral comet assay were measured in Dr. Hauser’s laboratory. They found an association between urinary concentrations of some phthalate metabolites, namely monobutyl phthalate, and decreased semen quality (sperm motility and concentration). There was also an association between urinary concentrations of monoethyl phthalate and increased sperm DNA damage. The public health implications of these results are potentially large since a majority of the population is exposed to phthalates at levels measured in the research study subjects. Furthermore, altered semen quality and sperm DNA damage may have implications for male fertility and for male-mediated adverse pregnancy outcomes, including pregnancy loss and potential birth defects.
Drs. Hauser and Ryan extended this work with more recently developed phthalate biomarkers (oxidative metabolites of phthalates) which provide a more integrated measure of exposure to the parent compound (Hauser, Meeker et al. 2006; Hauser, Meeker et al. 2007) The oxidative biomarkers are especially important for assessing exposure to di(2-ethylhexyl) phthalate, one of the most biologically active toxicants in experimental studies. The biomarker incorporated three DEHP metabolites into a single summary measure, and was referred to as the percent of DEHP excreted as MEHP (i.e., %MEHP). After accounting for this susceptibility biomarker, the associations between sperm DNA damage and some of the phthalate monoesters, primary MEHP, were stronger. This represented a new finding has led to new directions in phthalate research in our Organics research group.
Dr. Hauser’s phthalate studies have been used by national and international governmental agencies to guide policy. Examples include the review of some of his studies for the California initiative under Proposition 65 to restrict the use of some phthalates due to reproductive toxicity. The National Toxicology Program, Center for Evaluation of Risks to Human Reproduction, and the Integrated Risk Information System (IRIS), prepared and maintained by the U.S. Environmental Protection Agency, recently conducted reviews on phthalates. For these reviews, Dr. Hauser’s studies were some of the primary human studies on male reproductive function and phthalates.
Dr. Hauser also published three papers on the relationship of PCBs with reproductive health endpoints (Hauser, Chen et al. 2003; Hauser, Singh et al. 2003; Meeker, Altshul et al. 2007). They found associations between higher serum levels of some PCB congeners with poorer semen quality and lower circulating levels of thyroid hormones. He is currently analyzing serum samples for PCB metabolites, specifically OH-PCBs, which have been shown in experimental studies to inhibit sulfotransferase, an enzyme that metabolizes endogenous estrogens. The Center Organics Laboratory developed methods for the analysis of the OH-PCBs. They will explore the association of OH-PCBs, more biologically active than the parent compound, in relation to semen quality and pregnancy outcomes.