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％女性的主要公共卫生问题，这是 估计到2025年会影响650万美国妇女。此外，不育的比率是 随着妇女等待更长的孩子，预计会增加。女性不育的主要原因 与 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内分泌的化学暴露与女性联系起来 不育和过早的生殖老化。但是，只有其中一些研究检查了 尽管它们与女性有关 健康。特别是丙基培训是一种通常合并的抗菌化合物 在许多产品中，这是一个可疑的内分泌干扰器。有限的实验发现 表明它可以瞄准卵巢并改变性别立体骑马合成。但是，这些 研究主要使用新生儿和年轻啮齿动物，检查了短期暴露持续时间，以及 忽略了卵形促销苯甲酸酯的潜在靶标。此后，提议的项目 旨在确定长期暴露于丙酸培根对卵巢和卵巢的逐步影响 通过使用紧密模仿女性的动物模型，产卵功能和整体生育能力 暴露和生育选择。我们的中心假设是长期每天接触 丙酰亚前培养 以降低的生育能力导致暴露和剂量的持续时间（体内）加剧。 我们建议确定丙酸培训对1）卵巢类固醇发生的毒性作用。 和卵泡发育，2）输卵管上皮细胞更新和整体生育能力。为此，我们 将利用尖端的分子和组织形态学方法以及马酮测定法 和全面的生育研究。我们将比较三种不同剂量的丙酸培根和 暴露持续时间将在三个不同的育龄年龄中模仿妇女的暴露。 拟议项目的成功完成将提供机械和生理 对丙酰亚前培训对卵巢，卵形和整体生育的结果。我们的 拟议的研究可能会确定与加速生殖老化和 无法解释的不育。拟议研究的发现将提高妇女的能力 关于其复制健康的知情选择。