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: 7882642
• 负责人: Sakhila Banu
• 金额: $ 7.25万
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7882642
• 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）：世纪以来，六价铬（Cr（VI））已广泛用于各种行业，如Chrome、焊接、喷漆和金属表面处理。铬酸盐工业产生的Cr（VI）是一种重要的环境污染物。然而，尽管美国在保护和回收方面做出了努力，但每年仍有超过20，000公吨的Cr（VI）释放到环境中，其中超过5，000公吨作为大气排放物释放。因此，数以百万计的人，包括大多数产业工人，暴露于Cr（VI）。通过阴离子转运机制，Cr（VI）很容易进入细胞，其健康后果尚未完全了解。工业化国家的女性不孕症有所增加。在铬行业工作的妇女月经不正常，血液中的铬（六价铬）含量很高，可以通过乳汁从母亲传给后代。如果哺乳期妇女在铬行业工作或生活在暴露于高铬摄入量的地区，通过食物或饮用水母乳喂养其后代，有一个潜在的风险，在母亲的乳汁中的铬（VI）将影响卵巢发育的后代。哺乳期暴露于Cr（VI）对卵巢卵泡发育、青春期和发育中后代的生殖健康的毒性作用仍然是一个谜，铬毒性对卵巢发育的主要细胞和分子机制尚不清楚。这项研究的主要目的是揭示哺乳期暴露于Cr（VI）损害卵巢发育和诱导卵泡闭锁的机制。这一目标将通过检验哺乳期暴露于Cr（VI）损害卵巢卵泡发育并诱导后代卵泡闭锁和凋亡的假设来实现。我们的具体目标是：（1）确定哺乳期暴露于Cr（VI）对后代卵巢卵泡发育的影响，和（2）确定哺乳期暴露于Cr（VI）对后代卵巢卵泡闭锁和细胞凋亡的影响。哺乳期大鼠将在产后前三周通过饮用水暴露于Cr（VI），以便青春期前（哺乳期）大鼠通过母乳接受铬。将在出生后第25、35和65天研究Cr（VI）毒性对这些后代卵巢卵泡发育、卵泡闭锁和颗粒细胞凋亡的影响。将确定Cr（VI）对半胱天冬酶-3依赖性凋亡途径的影响。完成本项目中概述的研究，预计将提供新的知识，并增加对Cr（VI）诱导的毒性对卵巢卵泡发育和卵泡闭锁的机制的理解。这些研究结果从大鼠模型，然后可以转化为战略，保护妇女及其雌性后代的生殖健康，特别是那些暴露于铬，从而支持NIH和NIEHS的使命。公共卫生相关性：六价铬（Cr（VI））用于广泛的行业，数百万人和大多数产业工人在工作场所、垃圾填埋场和水道以及每天的大气排放中暴露于Cr（VI）废物。已知Cr（VI）会导致肺癌，破坏胚胎和胎儿发育，并导致女性生殖异常。本项目的重点是确定哺乳期暴露于Cr（VI）对卵巢卵泡发育和退化的影响（闭锁和凋亡）在其不同发育年龄的后代，因此，完成本项目中概述的研究应提供了解Cr（VI）机制所必需的新知识对卵巢卵泡发育和卵泡闭锁的毒性，可以转化为保护妇女的生殖健康，特别是那些在暴露于Cr（VI）的行业中工作的妇女。

项目成果

Postnatal exposure to chromium through mother's milk accelerates follicular atresia in F1 offspring through increased oxidative stress and depletion of antioxidant enzymes.

产后通过母乳接触铬会增加氧化应激和抗氧化酶的消耗，从而加速 F1 后代的卵泡闭锁。

• DOI: 10.1016/j.freeradbiomed.2013.02.006
• 发表时间: 2013
• 期刊: Free radical biology & medicine
• 影响因子: 7.4
• 作者: Stanley,JoneA;Sivakumar,KirthiramK;Nithy,ThamizhK;Arosh,JoeA;Hoyer,PatriciaB;Burghardt,RobertC;Banu,SakhilaK
• 通讯作者: Banu,SakhilaK