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(http://www.niehs.nih.gov//portfolio/index.cfm?do=portfolio.grantdetail&&grant_number=R01ES032290&format=word)
| Principal Investigator: Ying, Zhekang | |
|---|---|
| Institute Receiving Award | University Of Maryland Baltimore |
| Location | Baltimore, MD |
| Grant Number | R01ES032290 |
| Funding Organization | National Institute of Environmental Health Sciences |
| Award Funding Period | 09 Apr 2021 to 31 Jan 2026 |
| DESCRIPTION (provided by applicant): | ABSTRACT Considerable epidemiological studies reveal that maternal exposure to ambient fine particulate matter (PM2.5) poses a significant risk for obesity to the child. In animal models, we and others corroborate the adverse programming of offspring adiposity by maternal PM2.5 exposure and implicate the offspring’s hypermethylated and thus down-expressed Leptin in this adverse programming. In contrast, few published studies have tested the maternal pathogenesis for this adverse programming. In order to develop effective intervention strategies that may benefit both the mother and child, we propose to unravel its maternal pathogenesis using our unique genetically-modified animal models and state-of-the-art PM2.5 exposure technique. Through a synthesis of both published and preliminary data, we hypothesize that maternal PM2.5 exposure programs offspring Leptin expression and thus adiposity via maternal pulmonary inflammation and ensuing oocyte down-expression of Tet2, and propose to thoroughly test this hypothesis through pursuing three discrete yet linked aims: Aim 1: To model the dose- and composition-dependencies for the adverse programming of offspring adiposity by maternal PM2.5 exposure. Aim 2. To determine whether maternal PM2.5 exposure programs offspring adiposity through maternal oocyte down-expression of Tet2 and subsequent offspring down-expression of Leptin. Aim 3: To determine whether pulmonary inflammation induced by PM2.5 exposure elicits maternal oocyte disturbance and subsequent programming of offspring adiposity. By revealing the critical pathogenesis, this project is expected to provide a strong scientific framework for understanding of and developing interventions for the adverse programming of offspring adiposity by maternal PM2.5 exposure. |
| Science Code(s)/Area of Science(s) |
Primary: 51 - Obesity Secondary: 03 - Carcinogenesis/Cell Transformation |
| Publications | See publications associated with this Grant. |
| Program Officer | Thaddeus Schug |