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.

女性不孕症是影响约10%女性的重大公共卫生问题， 预计到 2025 年将影响 650 万美国女性。此外，不孕率 随着女性生育时间的延长，女性不孕的主要原因预计会增加。 涉及到 卵巢、输卵管（输卵管）或特发性功能障碍。 流行病学研究已将一些内分泌干扰化学物质暴露与女性联系起来 然而，这些研究中只有一部分进行了调查。 日常用品中的化学物质尽管与女性生殖相关，但仍具有生殖毒性作用 尤其是对羟基苯甲酸丙酯是一种常用的抗菌化合物。 在许多产品中，它被怀疑是一种内分泌干扰物，实验结果有限。 表明它可以靶向卵巢并改变性类固醇激素的合成。 研究主要使用新生儿和年轻成年啮齿动物，检查短暴露时间，并 从今以后，拟议的项目忽略了输卵管作为对羟基苯甲酸丙酯的潜在目标。 旨在确定长期接触对羟基苯甲酸丙酯对卵巢和卵巢的渐进影响 通过使用密切模仿女性的动物模型来研究输卵管功能和整体生育能力 我们的中心假设是长期每天接触。 对羟基苯甲酸丙酯破坏卵巢类固醇生成并减少输卵管上皮细胞更新， 最终导致生育能力下降，且因暴露时间和剂量（体内）而加剧。 我们建议确定对羟基苯甲酸丙酯对 1) 卵巢类固醇生成的生殖毒性影响 和卵泡发育，2）输卵管上皮细胞更新和整体生育能力。 将利用尖端的分子和组织形态学方法以及激素测定 我们将比较三种不同剂量的对羟基苯甲酸丙酯和综合生育力研究。 暴露的持续时间将模仿女性在三个不同育龄期间的暴露时间。 拟议项目的成功完成将提供机械和生理方面的帮助 关于对羟基苯甲酸丙酯对卵巢、输卵管和整体生育能力的生殖毒性影响的研究结果。 拟议的研究可能会发现与加速生殖衰老相关的新因素 拟议研究的结果将提高女性的生育能力。 有关其生殖健康的知情选择。