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: 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
• 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' 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.

女性不孕症是一个主要的公共卫生问题，影响约10%的妇女， 预计到2025年将影响650万美国女性。此外，不孕症的发病率 随着女性等待生育时间的延长，女性不孕的主要原因 涉及 卵巢、输卵管（输卵管）或特发性功能障碍。最近的实验和 流行病学研究表明， 不育和过早的生殖老化。然而，这些研究中只有一部分研究了 日用品中的化学品尽管与妇女的生殖健康有关， 健康对羟基苯甲酸丙酯是一种抗微生物化合物， 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类固醇激素的合成。但这些 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， 忽略了输卵管作为对羟基苯甲酸丙酯的潜在靶点。哈登，拟议中的项目 目的是确定长期暴露于尼泊金丙酯对卵巢的渐进性影响， 输卵管功能和整体生育能力，通过使用动物模型，密切模仿妇女的 暴露和生育选择。我们的中心假设是，长期每天暴露于 对羟基苯甲酸丙酯破坏卵巢类固醇生成并降低输卵管上皮细胞更新， 最终导致生育力降低，并因暴露持续时间和剂量（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作用 和卵泡发育，2）输卵管上皮细胞更新，和总体生育力。为此我们 将利用最先进的分子和组织形态学方法沿着激素检测 和全面的生育研究。我们将比较三种不同剂量的对羟基苯甲酸丙酯， 暴露持续时间将模拟女性在三个不同生育年龄的暴露。 成功完成拟议项目将提供机械和生理 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 拟议的研究可能会确定与加速生殖老化有关的新因素， 不明原因的不孕症拟议研究的结果将提高妇女的能力， 对生殖健康作出知情选择。