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

• 批准号: 10373441
• 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
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373441
• 关键词: Adult; Affect; Age; Aging; American; Animal Model; Antral; Apoptosis; Beauty; Beverages; Biological; Biological Assay; Cancerous; Cell Count; 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; Lead; 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; Pregnancy Complications; Premature Ovarian Failure; Public Health; Reproductive Health; Rodent; Sampling; Secretory Cell; Serum; Steroid biosynthesis; Testing; Tissues; Toxicology; Urine; Woman; Women' 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

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.

女性不孕不育是一个主要的公共卫生问题，影响着大约10%的女性，而且它是 据估计，到2025年，将影响650万美国女性。此外，不孕不育率是 随着女性等待生育的时间更长，预计这一数字将会增加。女性不孕不育的主要原因 与…有关 卵巢、输卵管(输卵管)或特发性功能障碍。最近的实验和 流行病学研究已将某些干扰内分泌的化学物质暴露与女性联系起来。 不孕不育和生殖早衰。然而，这些研究中只有一些研究检查了 日常使用产品中化学物质的生殖毒性影响，尽管它们与女性的 健康。特别是，对羟基苯甲酸丙酯是一种抗菌化合物，通常被 在许多产品中，它是一种可疑的内分泌干扰物。有限的实验结果 表明它可以靶向卵巢并改变性激素的合成。然而，这些 研究主要使用了新生和年轻的成年啮齿动物，检查了短期接触时间，以及 忽略了输卵管作为帕拉苯丙酯的潜在靶点。从今以后，提议的项目 目的是确定长期接触对苯丙胺对卵巢和卵巢的渐进性影响。 输卵管功能和总体生育力通过使用接近模拟女性的 曝光率和生育选择。我们的中心假设是，长期的日常接触 对羟基苯甲酸丙酯干扰卵巢类固醇合成并降低输卵管上皮细胞周转， 最终导致生育力下降，并因暴露时间和剂量(在体内)而加剧。 我们建议确定对羟基苯甲酸丙酯对1)卵巢类固醇生成的再生殖毒性作用 和卵泡发育，2)输卵管上皮细胞周转，和总体生育力。为此，我们 将利用尖端的分子和组织形态方法以及激素分析 和全面的生育研究。我们将比较三种不同剂量的帕拉苯丙酯和 暴露的持续时间将模拟妇女在三个不同生育年龄期间的暴露。 拟议项目的成功完成将提供机械和生理上的 关于对羟基苯甲酸丙酯对卵巢、输卵管和总体生育力影响的研究结果。我们的 拟议的研究可能会确定与加速生殖衰老和 不明原因的不孕症。拟议中的研究结果将提高女性的 关于她们生殖健康的知情选择。