Male pesticide exposure, reproductive health and epigenetics

项目总结

PROJECT SUMMARY Infertility is estimated to affect ~15% of all couples worldwide and male factors account for 40% of infertility among couples. Only ~10% of U.S. reproductive age women get pregnant each year and only ~60% are intended pregnancies. Despite the increasing use of medical treatment among couples with decreased fecundity, success rates of live birth have remained stable. Thus, identifying modifiable factors, such as environmental exposures, that can impact human fertility is a major clinical and public health matter. Intake of fruits and vegetables in the U.S. general population is the primary source of exposure to non-persistent pesticides, which has been associated with different adverse health effects, including infertility, reproductive disorders, and pregnancy and perinatal complications. While it has been shown that paternal environmental exposures may impact the sperm epigenome and consequently offspring health, no epidemiological studies to date have explored pregnancy and perinatal effects of paternal pesticide exposure and potential biological mechanisms that explain the associations. To address these important knowledge gaps, we aim to determine the association of male urinary concentrations of pesticide biomarkers (individually and as a mixture) with semen parameters, sperm DNA methylation and mitochondrial DNA biomarkers (aim 1), with pregnancy and perinatal outcomes adjusting for female urinary pesticide biomarkers (aim 2), and also with epigenetic aging in semen and leukocytes. Epigenetic age or DNA methylation aging biomarkers have recently emerged as excellent biomarkers of age-related diseases such as infertility and reproductive health. To examine these novel aims, we will leverage two prospective cohorts of couples attending fertility centers: the Environment and Reproductive Health (EARTH) Study in Boston, MA (main study), and the Sperm Environmental Epigenetics and Development Study (SEEDS) in Springfield, MA (validation study). The proposed study will increase our understanding of non-occupational pesticide exposure for a relatively understudied area of male reproductive health and will also open an important area of inquiry into better understanding of how paternal environmental exposures can impact couples’ and offspring’s health and potential biologic mechanisms linking the paternal environment to his children’s health. Most importantly, this project addresses strategic priorities of the National Institute of Environmental Health Sciences (NIEHS) for advancing environmental health sciences, including assessing coexposures and individual susceptibility to environmental chemicals. We are currently collecting detailed health measures on children who were born to couples who participated in the EARTH Study to determine the extent to which paternal and maternal preconception environmental exposures are associated with neurodevelopmental and metabolic endpoints. Incorporating the assessment of exposure to several classes of pesticides will provide data that can be linked in future studies on children’s health outcomes.