Effects of Lactational Exposure to Chromium (VI) on Ovarian Development

哺乳期接触铬 (VI) 对卵巢发育的影响

• 批准号: 7586930
• 负责人: Sakhila Banu
• 金额: $ 7.33万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7586930
• 关键词: Adult; Adverse effects; Affect; Age; Ammonium; Anabolism; Anions; Apoptosis; Apoptotic; Area; Atretic Follicles; Biological Assay; Blood; Bos taurus PARP protein; Breast Feeding; Carcinogens; Cell Proliferation; Cells; Cesium; Chromates; Chromium; Data; Delayed Puberty; Deposition; Developed Countries; Development; Diestrus; Diet; Dose; Embryonic and Fetal Development; Environment; Environmental Hazards; Estradiol; Estrous Cycle; Estrus; Exposure to; Female; Female infertility; Fertility; Fetus; Follicle Stimulating Hormone; Follicular Atresia; Food; Goals; Health; Histology; Hormones; Hydrogen; Immunohistochemistry; In Vitro; Industry; Intake; Knowledge; Label; Life; Lithium; Lung; Luteinizing Hormone; Malignant neoplasm of lung; Measures; Menstruation; Metals; Metestrus; Metric; Milk; Mission; Modeling; Molecular; Mono-S; Mothers; Mutagens; National Institute for Occupational Safety and Health; National Institute of Environmental Health Sciences; Organ; Ovarian; Ovarian Tissue; Ovary; Ovulation; Pathway interactions; Placenta; Plasma; Postpartum Period; Potassium; Process; Proestrus; Proteins; Puberty; Radioimmunoassay; Rattus; Recycling; Reproductive Health; Research; Research Project Grants; Risk; Rodent; Rubidium; Sodium; Staging; Testing; Time; Tissues; Toxic effect; Translating; United States; United States National Institutes of Health; Water; Welding; Woman; Work; Working Women; Workplace; base; caspase-3; cell type; chromium hexavalent ion; drinking water; experience; granulosa cell; inhibitor/antagonist; killings; landfill; lead chromate; meetings; offspring; postnatal; pregnant; prepuberty; public health relevance; pup; reproductive; research study; wasting

DESCRIPTION (provided by applicant): Hexavalent chromium, Cr(VI), has been used in a wide-range of industries, such as chrome plating, welding, painting, and metal finishes, for more than a century. Cr(VI) deposited as waste in landfills and waterways by chromate industries is a significant potential environmental hazard. Despite conservation and recycling efforts in the United States, however, over 20,000 metric tons of Cr(VI) are released into the environment every year with over 5,000 metric tons released as atmospheric emissions. Consequently, millions of people, including a majority of industrial workers, are exposed to Cr(VI). By an anion transport mechanism Cr(VI) readily enters the cell and the health consequences are not fully understood. Female infertility has increased in industrialized countries. Women working in Cr industries experience abnormal menses and have high blood levels of Cr(VI) that can be transported from mother to offspring through milk. If lactating women working in a Cr industry or living in an area exposed to high Cr intake through food or drinking water breast-feed their offspring, there is a potential risk that Cr(VI) in the mother's milk will affect ovarian development of the offspring. Toxic effects resulting from lactational exposure to Cr(VI) on ovarian follicular development, puberty, and reproductive health of developing offspring remain an enigma, and the principal cellular and molecular mechanisms underlying chromium toxicity on ovarian development are not known. The primary goal of the proposed research is to unravel the mechanisms by which lactational exposure to Cr(VI) impairs ovarian development and induces follicular atresia. This aim will be met by testing the hypothesis that lactational exposure to Cr(VI) impairs ovarian follicular development and induces follicular atresia and apoptosis in the offspring. Our Specific Aims are to: (1) Determine the effects of lactational exposure to Cr(VI) on ovarian follicular development in the offspring, and (2) Determine the effects of lactational exposure to Cr(VI) on ovarian follicular atresia and apoptosis in the offspring. Lactating rats will be exposed to Cr(VI) through drinking water during the first three weeks of postpartum so that the prepubertal (suckling) rats will receive chromium through mother's milk. Effects of Cr(VI) toxicity on ovarian follicular development, follicular atresia and granulosa cell apoptosis will be studied in these offspring on postnatal days 25, 35 and 65. Effect of Cr(VI) on caspase-3 dependent apoptotic pathway will be determined. Completion of studies outlined in this project are expected to provide new knowledge and increased understanding of mechanisms responsible for Cr(VI)-induced toxicity on ovarian follicular development and follicular atresia. These findings from a rat model can then be translated to strategies for protection of the reproductive health of women and their female offspring, especially those exposed to Cr, and thus support the missions of NIH and NIEHS. PUBLIC HEALTH RELEVANCE: Hexavalent chromium, Cr(VI), is used in a wide-range of industries, and millions of people and a majority of industrial workers have been exposed to Cr(VI) wastes in the workplace, landfills and waterways and every day atmospheric emissions. Cr(VI) is known to cause lung cancers, disrupt embryo and fetal development and induce reproductive abnormalities in women. The focus of the present project is to determine the effects of lactational exposure to Cr(VI) on ovarian follicular development and degeneration (atresia and apoptosis) in the offspring during their different developmental ages, and thus completion of studies outlined in this project should provide new knowledge essential to understand the mechanism of Cr(VI) toxicity on ovarian follicular development and follicular atresia which can be translated to protect reproductive health of women, especially those working in industries in which they are exposed to Cr(VI).

描述（由申请人提供）：一个多世纪以来，已在诸如镀铬，焊接，绘画，绘画和金属饰面之类的广泛行业中使用了六价铬（VI）。 CR（VI）作为垃圾填埋场和水道上的废物沉积的CR（VI）是一种巨大的潜在环境危害。尽管在美国进行了保护和回收工作，但是每年将超过20,000吨的CR（VI）释放到环境中，其中超过5,000公吨作为大气排放。因此，包括大多数工业工人在内的数百万人暴露于CR（VI）。通过阴离子运输机制CR（VI）很容易进入细胞，并且没有完全了解健康后果。工业化国家的女性不孕症有所增加。在CR行业工作的妇女经历了异常的月经，并且具有高血液的CR（VI），可以通过牛奶从母亲到后代运输。如果哺乳使在CR行业工作的妇女或居住在通过食物或饮用水饲养后代的地区的地区，则可能会有母亲牛奶中的CR（VI）可能会影响后代的卵巢发育。乳酸（VI）暴露于CR（VI）引起的毒性作用对发展后代的卵巢卵泡发育，青春期和生殖健康仍然是一个谜，并且尚不清楚铬毒性的主要细胞和分子机制。拟议的研究的主要目标是揭示泌乳暴露（VI）损害卵巢发育并诱导卵泡闭锁的机制。通过测试乳酸暴露于Cr（VI）会损害卵巢卵泡发育并诱导后代的卵泡闭锁和凋亡的假设来实现此目标。我们的具体目的是：（1）确定对后代卵巢卵泡发育的泌乳（VI）的影响；（2）（2）确定乳酸暴露于CR（VI）对卵巢卵泡腹膜闭锁和卵巢卵的影响。在产后的前三周，泌乳大鼠将通过饮用水暴露于CR（VI），以便前（哺乳）大鼠通过母亲的牛奶接收铬。 CR（VI）毒性对卵巢卵泡发育，卵泡闭锁和颗粒细胞细胞凋亡的影响将在产后第25、35和65天的这些后代进行研究。将确定CR（VI）对CASPASE-3依赖性凋亡途径的影响。预计该项目中概述的研究的完成将提供新的知识，并增加对导致CR（VI）诱导的毒性毒性造成卵泡发育和卵泡闭锁的机制的理解。然后，这些大鼠模型的发现可以转化为保护妇女及其女性后代生殖健康的策略，尤其是暴露于CR的后代，从而支持NIH和NIEHS的任务。公共卫生相关性：六价铬，CR（VI），用于广泛的行业，数以百万计的人和大多数工业工人被暴露于工作场所，垃圾填埋场和水道和每天大气的大气上的CR（VI）废物。众所周知，CR（VI）会引起肺癌，破坏胚胎和胎儿发育，并引起女性的生殖异常。 The focus of the present project is to determine the effects of lactational exposure to Cr(VI) on ovarian follicular development and degeneration (atresia and apoptosis) in the offspring during their different developmental ages, and thus completion of studies outlined in this project should provide new knowledge essential to understand the mechanism of Cr(VI) toxicity on ovarian follicular development and follicular atresia which can be translated to protect妇女的生殖健康，尤其是那些从事CR（VI）的行业工作的人。