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Propylparaben effects on reproductive health of the aging female

对羟基苯甲酸丙酯对老年女性生殖健康的影响

基本信息

批准号：
10526421
负责人：
Matthew J Dean
金额：
$ 7.93万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-12-01 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10526421
关键词：
Acceleration Adult Affect Age Aging American Animal Model Antral Apoptosis Beauty Beverages Biological Biological Assay Cancerous Cell Count Cell Cycle Inhibition Cell Cycle Progression Cell Death Cell Density Cell Proliferation Chemical Exposure Chemicals Child Childbirth Data Dermal Development Dose Endocrine Disruptors Environment Enzymes Epidemiology Epithelial Cells Estradiol Evaluation Exposure to Female Female infertility Fertility Fertility Study Follicle Stimulating Hormone Food Functional disorder Future Gonadal Steroid Hormones Growth Half-Life Hormones Human Milk Impairment In Vitro Infertility Ingestion Inhalation Knowledge Life Link Long-Term Effects Mammalian Oviducts Mammary Gland Parenchyma Measures Medical Medicine Methods Molecular Mus Neonatal Organ Outcome Ovarian Ovarian Follicle Ovary Parabens Pathway interactions Physiological Predisposition Pregnancy Complications Premature Ovarian Failure Proliferating Public Health Reproductive Health Rodent Sampling Secretory Cell Serum Steroid biosynthesis Testing Tissues Toxicology Urine Woman Women&apos s Health Work absorption antimicrobial child bearing economic cost epidemiology study experience experimental study hormonal signals idiopathic infertility improved in vivo neglect novel ovarian reserve premature psychosocial reproductive hormone reproductive outcome reproductive senescence therapy development transcriptome sequencing trend young adult

项目摘要

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.

女性不孕症是影响约10%妇女的主要公共卫生问题，确实如此