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Principal Investigator: Kuzmanov, Aleksandra
Institute Receiving Award Lawrence Technological University
Location Southfield, MI
Grant Number R15ES034520
Funding Organization National Institute of Environmental Health Sciences
Award Funding Period 24 Feb 2024 to 31 Jan 2027
DESCRIPTION (provided by applicant): Project Summary/Abstract Accumulating evidence shows that bisphenol A (BPA) affects not only the development and growth of reproductive tissues, but also disrupts female meiosis. The interference of BPA with the meiotic process leads to the formation of reproductive cells with an incorrect number of chromosomes, resulting in the inability to conceive, pregnancy loss, and developmental disabilities in offspring. In recent years, increasing health concerns led manufacturers to seek BPA alternatives, which has resulted in its replacement with bisphenol F (BPF) and bisphenol S (BPS), for example, in some consumer products. However, numerous studies have indicated that currently available bisphenol analogs resemble BPA in their ability to interfere with hormones and cause meiotic errors. The long-term goal of the proposed collaborative research project is to understand the relationship between bisphenol structure and meiotic fidelity. To this end, we aim to identify bisphenol analogs that pose low or no risk to human reproductive health. This objective will be accomplished through two specific aims: (1) Synthesis of a library of novel, structurally diverse bisphenol analogs via phenolic ring substitutions, which have shown particular promise in mediating lower toxicity in studies involving tetramethylbisphenol F; and (2) Identification of BPA analogs that pose low or no risk to meiosis using several C. elegans-based assays. These assays will include the monitoring of C. elegans brood size, germ-cell apoptosis, embryonic lethality, and the incidence of males that arise as the result of a meiotic error. Bisphenol candidates posing low or no risk to meiosis will be further evaluated for their endocrine-disrupting properties using a validated human cell-based assay. Understanding how the structure of bisphenols affect reproductive health could lead to the replacement of this ubiquitous reproductive toxin with a safer alternative in consumer products. Furthermore, this innovative proposal will significantly strengthen the research environment in the Department of Natural Sciences at the Lawrence Technological University by providing our undergraduate students with the opportunity to participate in a funded, multidisciplinary project with great societal relevance.
Science Code(s)/Area of Science(s) Primary: 72 - Predictive Toxicology/Assay Development
Secondary: 03 - Carcinogenesis/Cell Transformation
Publications No publications associated with this grant
Program Officer Lingamanaidu Ravichandran
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