Export to Word (http://www.niehs.nih.gov//portfolio/index.cfm?do=portfolio.grantdetail&&grant_number=R03ES032887&format=word)
Principal Investigator: Ziv-Gal, Ayelet
Institute Receiving Award University Of Illinois At Urbana-Champaign
Location Champaign, IL
Grant Number R03ES032887
Funding Organization National Institute of Environmental Health Sciences
Award Funding Period 01 Dec 2021 to 30 Nov 2024
DESCRIPTION (provided by applicant): Female infertility is a major public health problem that affects about 10% of women and it is estimated to affect 6.5 million American women by 2025. Additionally, rates of infertility are expected to increase as women wait longer to have children. The main reasons of female infertility relate to ovarian, fallopian tube (oviduct), or idiopathic dysfunctions. Recent experimental and epidemiological studies have linked some endocrine disrupting chemical exposures with female infertility and premature reproductive aging. However, only some of these studies have examined the reprotoxic effects of chemicals in daily-used products despite their relevance to women’s health. Propylparaben, in particular, is an antimicrobial compound that is commonly incorporated in numerous products and it is a suspected endocrine-disruptor. Limited experimental findings indicate that it can target the ovary and to alter sex steroid hormone synthesis. However, these studies mostly used neonatal and young adult rodents, examined short exposure durations, and neglected the oviduct as a potential target of propylparaben. Henceforth, the proposed project aims to determine the progressive effects of long-term exposure to propylparaben on ovarian and oviductal function and overall fertility by using an animal model that closely mimic women’s exposure and childbearing choices. Our central hypothesis is that long-term daily exposure to propylparaben disrupts ovarian steroidogenesis and decreases oviductal epithelial cell turnover, culminating with reduced fertility that is exacerbated by duration of exposure and dose (in vivo). We propose to determine the reprotoxic effects of propylparaben on 1) ovarian steroidogenesis and follicle development, 2) oviductal epithelial cell turnover, and overall fertility. To that end we will utilize cutting-edge molecular and histomorphological methods along with hormone assays and comprehensive fertility studies. We will compare three different doses of propylparaben and durations of exposure that will mimic women’s exposure during three different childbearing ages. The successful completion of the proposed project will provide both mechanistic and physiologic findings on propylparaben reprotoxic effects on the ovary, oviduct, and overall fertility. Our proposed studies may identify novel factors related to accelerated reproductive aging and unexplained infertility. Findings from the proposed studies will improve women’s ability to make informed choices about their reproductive health.
Science Code(s)/Area of Science(s) Primary: 66 - Female Reproduction
Secondary: 03 - Carcinogenesis/Cell Transformation
Publications See publications associated with this Grant.
Program Officer Thaddeus Schug