Water disinfection by-products and female fertility

水消毒副产物与女性生育能力

• 批准号: 9564588
• 负责人: Jodi A. Flaws
• 金额: $ 19.83万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9564588
• 关键词: Achievement; Acids; Adult; Affect; Age; Antral; Apoptosis; Area; Cells; Cessation of life; Chemicals; Cholera; Chronic; Chronic Disease; Data; Development; Disease; Disinfectants; Disinfection; Enzymes; Estradiol; Evaluation; Exposure to; Female; Fertility; Gene Proteins; Goals; Gonadal Steroid Hormones; Growth; Health Hazards; In Vitro; Incidence; Infertility; Iodoacetic Acid; Lead; Link; Molecular; Mus; Oocytes; Ovarian; Ovarian Follicle; Ovary; Oxidative Stress; Pathway Analysis; Pathway interactions; Prevention strategy; Process; Production; Proteins; Public Health; Regulation; Reporting; Reproduction; Reproductive Health; Research; Series; Steroid biosynthesis; System; Testing; Time; Toxic effect; Typhoid Fever; Water; Woman; Work; anthropogenesis; base; cancer risk; contaminated drinking water; drinking water; epidemiology study; experimental study; female fertility; granulosa cell; in vivo; mouse model; novel; reproductive; reproductive toxicity; subfertility; transcriptome sequencing; virtual; waterborne

The disinfection of drinking water was an important public health achievement of the 20th century because it significantly reduced the numbers of deaths and illnesses from drinking contaminated water. The disinfection process, however, leads to the production of water disinfection by-products (DBPs), which have been linked to toxicity in numerous systems. A major chemical class of DBPs includes the haloacetic acids (HAAs) such as iodoacetic acid (IAA), bromoacetic acid (BAA), and chloroacetic acid (CAA). Although previous studies indicate that some HAA exposures are associated with increased cancer risk, virtually nothing is known about the effects of adult exposure to IAA, BAA, and CAA on the ovary and female fertility. It is important to determine whether adult exposure to HAAs causes ovarian toxicity because women are exposed to HAAs daily, and ovarian toxicity often leads to female subfertility or infertility. Thus, we examined the effects of IAA, BAA, and CAA on the main functional unit of the ovary, the antral follicle. Our preliminary data indicate that environmentally relevant levels of IAA, BAA, and CAA significantly inhibit growth of antral ovarian follicles and the ability of antral follicles to produce the sex steroid hormone estradiol (E2). Slow follicle growth and low E2 levels are of concern because they are linked to increased atresia (death of follicles) and subfertility/infertility. Although preliminary data suggest that the selected HAAs may reduce fertility, they do not directly determine whether this is the case because they were obtained from in vitro studies. Thus, the goal of the proposed studies is to test the hypothesis that IAA, BAA, and CAA lead to gene/protein changes in the ovary to cause female subfertility/infertility. To test his hypothesis, these studies will: 1) determine whether and how HAAs (IAA, BAA, and CAA) inhibit ovarian follicle growth and cause female subfertility/infertility and 2) identify the molecular factors that are altered by HAAs (IAA, BAA, and CAA) and determine their relationship to altered follicle growth and female subfertility/infertility. This will be the first work to examine the effects of adult exposure to HAAs on the ovary and female fertility. As such, it will open a new area of research, which is critical for helping determine whether the selected HAAs are female reproductive health hazards and should be considered for regulation of use in adult women.

饮用水消毒是20世纪重要的公共卫生成就，因为 它大大减少了因饮用受污染的水而死亡和患病的人数。的 然而，消毒过程导致水消毒副产物（DBPs）的产生， 在许多系统中与毒性有关。消毒副产物的主要化学类别包括卤乙酸 酸（哈斯）如碘乙酸（IAA）、溴乙酸（BAA）和氯乙酸（CAA）。 尽管先前的研究表明，一些HAA暴露与癌症风险增加有关， 几乎没有人知道成年人暴露于IAA、BAA和CAA对卵巢的影响， 女性生育能力确定成人暴露于哈斯是否会引起卵巢毒性是重要的 因为女性每天暴露于哈斯，卵巢毒性通常导致女性生育力低下， 不孕因此，我们研究了IAA、BAA和CAA对卵巢主要功能单位的影响， 窦状卵泡我们的初步数据表明，环境相关水平的IAA，BAA和CAA 显著抑制有腔卵泡的生长和有腔卵泡产生性能力 类固醇激素雌二醇（E2）。卵泡生长缓慢和E2水平低是值得关注的，因为它们 与闭锁（卵泡死亡）和生育力低下/不育增加有关。尽管初步数据显示 虽然选择的哈斯可能会降低生育力，但他们并不直接确定是否如此，因为 它们从体外研究中获得。因此，拟议研究的目标是检验假设 IAA、BAA和CAA导致卵巢中的基因/蛋白质变化，从而导致女性生育力低下/不育。 为了验证他的假设，这些研究将：1）确定哈斯（IAA，BAA和CAA）是否以及如何抑制 卵泡生长和导致女性生育力低下/不育和2）确定的分子因素， 改变由哈斯（IAA，BAA和CAA），并确定它们的关系，改变卵泡生长和女性 低生育力/不育。这将是第一项研究成人暴露于哈斯对 卵巢和女性生育能力。因此，它将开辟一个新的研究领域，这对于帮助确定 所选哈斯是否对女性生殖健康有害，是否应考虑 成年女性使用的规定。