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(http://www.niehs.nih.gov//portfolio/index.cfm?do=portfolio.grantdetail&&grant_number=F31ES032631&format=word)
| Principal Investigator: Henderson, Ayana | |
|---|---|
| Institute Receiving Award | Harvard Medical School |
| Location | Boston, MA |
| Grant Number | F31ES032631 |
| Funding Organization | National Institute of Environmental Health Sciences |
| Award Funding Period | 01 Jun 2021 to 31 May 2024 |
| DESCRIPTION (provided by applicant): | Epidemiological and experimental data suggest that exposure to endocrine disrupting chemicals (EDCs) are linked to reproductive health issues including infertility, miscarriages, stillbirths, birth defects, and altered fetal development. Interestingly, some effects induced by EDC exposure have been shown to impact generations that extend beyond directly exposed individuals, suggesting that environmental toxins have transgenerational effects. Despite these indications, few studies have focused on the direct effects of EDCs on the germline. Furthermore, while humans are exposed to constant and variable mixtures of EDCs, most EDC studies have focused solely on the effects of single chemicals. Thus, understanding the additive, synergistic, and antagonistic effects between and among these chemicals is critical to understanding the risks they pose to human health. Because this is a daunting task in humans, I will combine studies in C. elegans and mice to test the efficacy of rapid screening in worms as a method of establishing relationships among common contaminants and assessing effects of chemical mixtures on the germline. My studies will focus specifically on a well characterized class of EDCs, namely phthalates, which are alkyl diesters of phthalic acid and widely used plasticizers found in various consumer, medical, and building products. Using six specific phthalates recently identified in human maternal urine, our preliminary studies found that individual exposure to BBP, DBP, DEP, DiBP, DiNP, and DEHP significantly increases chromosome nondisjunction and germ cell apoptosis during oogenesis in C. elegans. In this proposal, I aim to further characterize the individual effects of two of these phthalates (BBP and DEP) on chromosome morphogenesis, meiotic progression, germline-specific gene expression, and the chromatin landscape in both the female and male germlines. Lastly, I aim to determine the effects of all six phthalates in combination, as they exist in our environment, and assess how these effects are conserved across species. These proposed studies will not only shed light on the individual and combinatorial effects of these phthalates on both the female and male germlines, but the efficacy of using C. elegans to rapidly assess and predict the effects of environmental toxins on higher order organisms. |
| Science Code(s)/Area of Science(s) |
Primary: 50 - Endocrine System Secondary: 03 - Carcinogenesis/Cell Transformation |
| Publications | No publications associated with this grant |
| Program Officer | Thaddeus Schug |