Oxidative stress as a mediator of environmental exposure impacts on fertility endpoints

氧化应激作为环境暴露影响生育终点的中介因素

• 批准号: 10008733
• 负责人: Kelly Ferguson
• 金额: $ 10.85万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10008733
• 关键词: Address; Antral; Area; Biological Markers; Boston; Chemical Exposure; Chemicals; Clinical; Comet Assay; Couples; DNA; DNA Damage; Data; Economic Burden; Environment; Environmental Exposure; Environmental Health; Environmental Pollution; Exposure to; Female; Female infertility; Fertility; Fertilization in Vitro; General Hospitals; Germ Cells; Goals; Infertility; Link; Lipid Peroxidation; Literature; Live Birth; Massachusetts; Measures; Mediation; Mediator of activation protein; Morphology; Oocytes; Outcome; Oxidative Stress; Paper; Population; Pregnancy; Pregnancy Outcome; Pregnancy loss; Prevention; Prospective cohort; Psychological Stress; Reproductive Health; Research; Seminal fluid; Sperm Count Procedure; Statistical Data Interpretation; Woman; cell motility; implantation; infertility treatment; male; men; phthalates; recruit; reproductive; sperm cell; success; toxicant; urinary

Understanding the origins of infertility is an important area of environmental health research, as it impacts a substantial proportion of the population and leads to heavy economic burden of treatment and psychological stress. Identifying chemical exposures and underlying mechanisms of toxicant action may enable prevention of these consequences. Urinary phthalate metabolites have been associated with poor fertility outcomes in men, including semen quality parameters such as sperm count, morphology, and motility, as well as sperm DNA integrity. Further, phthalates have been linked to adverse in vitro fertilization (IVF) outcomes in men and women from infertile couples. The strongest associations observed in this body of literature are between phthalate exposure in men and decline in semen quality and increased sperm DNA damage, and between phthalate exposure in infertile women and poorer IVF outcomes (including oocyte yield, clinical pregnancy, and live birth). We hypothesize that oxidative stress is an important mechanism by which phthalates may adversely impact fertility and IVF success. To investigate this question, this study uses data from the Environment and Reproductive Health (EARTH) study, an ongoing prospective cohort begun in 2004 of couples seeking fertility treatment, conducted at Massachusetts General Hospital (MGH) in Boston, MA, USA. In this population recruitment is ongoing, and fertility measures include oocyte yield and antral follicle count, which will be examined in relation to female oxidative stress concentrations, and fertility and pregnancy outcomes (oocyte yield, antral follicle count, implantation, pregnancy loss, and live birth) which will be examined in relation to both male and female oxidative stress levels. In addition, we will investigate mediation of the observed associations between phthalate exposure and fertility and pregnancy endpoints by oxidative stress. Last years progress Over the past year we have completed analysis of urinary oxidative stress biomarkers and have begun statistical analyses to address our primary research questions. One paper is under revision and another is in progress.

了解不孕症的起源是环境卫生研究的一个重要领域，因为它影响到相当大比例的人口，并导致沉重的治疗经济负担和心理压力。确定化学品接触和潜在的毒性作用机制可能有助于预防这些后果。尿邻苯二甲酸酯代谢物与男性较差的生育结果有关，包括精液质量参数，如精子数量、形态、活力以及精子DNA完整性。此外，邻苯二甲酸盐与不孕夫妇的不良体外受精（IVF）结果有关。本文献中观察到的最强关联是男性接触邻苯二甲酸盐与精液质量下降和精子DNA损伤增加之间的关联，以及不孕女性接触邻苯二甲酸盐与较差的体外受精结果（包括卵母细胞产量、临床妊娠和活产）之间的关联。我们假设氧化应激是邻苯二甲酸盐可能对生育能力和体外受精成功产生不利影响的重要机制。