Role of endocrine-disrupting chemicals and social stress on perinatal outcomes

项目摘要/摘要 我的K99/R00职业发展计划的目标是在 内分泌干扰物的生殖和环境流行病学，包括 评估可能影响重叠生物途径的健康的社会决定因素。要做到这一点 目标，我将通过教学和实践培训来增强我在环境健康科学方面的专业知识 生殖生物学、社会流行病学/应激科学和环境流行病学方法。这 专业培训将使我实现成为一名独立学者的长期目标 调查员，并就环境和社会因素对 生殖健康。 我的研究计划的主要目标是评估多溴联苯的独立效果。 多溴联苯醚(PBDEs)和心理社会应激对甲状腺激素紊乱及其围产儿结局的影响 在社会经济和种族多元化的孕妇群体中。这项工作特别是 创新，因为多溴二苯醚和心理社会压力都会影响甲状腺系统，这表明 交互作用的似是而非，然而，这两种接触从未在人类身上同时进行过检查 学习。在K99指导阶段，在Tracey Woodruff博士的主要指导下，我将使用 创新措施，以确定与生物相关的多溴二苯醚暴露和心理社会压力的特征以及 它们对甲状腺激素紊乱的影响。将使用两种多溴二苯醚同系物来评估对多溴二苯醚的暴露 以及它们的羟化代谢物(OH-PBDEs)。心理社会压力将用主观评价 压力和端粒长度的测量，端粒长度是细胞衰老的生物标志，受到心理社会压力的影响。 在独立阶段，我将应用这些知识来研究多溴二苯醚和 心理社会应激对不良围产儿结局的影响，如妊娠期高血压、早产和低血压 出生体重，并评估这些影响是否通过甲状腺系统调节。这一点的整合 工作将使我能够制定必要的方法学和生物学框架，以审查 环境和心理社会因素对围产儿结局的综合影响和潜在的协同作用 在未来的R01研究中。我很有能力在加州大学旧金山分校实现这些目标 弗朗西斯科是一家备受尊敬的研究机构，拥有强大的环境生殖健康计划， 世界知名的教师，拥有心理社会压力方面的专业知识，以及广泛的生物医学基础设施。我的 生殖科学、环境流行病学、健康差距、 强调科学，生物统计学将指导我学习所需的方法 完成本提案中提出的目标。这个项目代表了健康差距的前沿 和环境健康研究，并寻求回答关键的科学和政策相关的问题 用于改善弱势人群的健康，他们经常面临不成比例的和更高的接触 多种化学和非化学应激源。

Project Summary/Abstract The goal of my K99/R00 career development plan is to launch an independent research program in reproductive and environmental epidemiology of endocrine-disrupting chemicals (EDCs) which includes evaluating social determinants of health that may affect overlapping biologic pathways. To accomplish this goal, I will enhance my expertise in environmental health sciences with didactic and hands-on training in reproductive biology, social epidemiology/stress science, and environmental epidemiologic methods. This specialized training will allow me to achieve my long term goal of becoming an independent academic investigator and offering new insights on the cumulative impacts of environmental and social factors on reproductive health. The primary goal of my research plan is to evaluate the independent effects of polybrominated diphenyl ethers (PBDEs) and psychosocial stress on thyroid hormone disruption and consequent perinatal outcomes among a population of socioeconomically and racially diverse pregnant women. This work is particularly innovative as both PBDEs and psychosocial stress can impact the thyroid system, suggesting a biologic plausibility for interaction, however the two exposures have never been examined simultaneously in a human study. During the K99 mentored phase, under the primary mentorship of Dr. Tracey Woodruff, I will use innovative measures to characterize biologically-relevant exposures to PBDEs and psychosocial stress and their effects on thyroid hormone disruption. Exposure to PBDEs will be assessed using both PBDE congeners as well as their hydroxylated metabolites (OH-PBDEs). Psychosocial stress will be evaluated with subjective measures of stress and telomere length, a biomarker of cellular aging that is influenced by psychosocial stress. In the independent phase, I will apply this knowledge to investigate the independent effects of PBDEs and psychosocial stress on adverse perinatal outcomes, such as gestational hypertension, preterm birth, and low birth weight, and assess whether these effects are mediated via the thyroid system. The integration of this work will enable me to develop the necessary methodological and biological frameworks to examine the combined, and potentially synergistic, effects of environmental and psychosocial factors on perinatal outcomes in future R01 studies. I am well positioned to accomplish these goals at the University of California, San Francisco, a highly respected research institution, with a strong environmental reproductive health program, a world-renowned faculty with expertise in psychosocial stress, and an extensive biomedical infrastructure. My primary mentor and co-mentors in reproductive sciences, environmental epidemiology, health disparities, stress science, and biostatistics will guide the process whereby I learn the methods that are required to accomplish the goals set forth in this proposal. This project represents the cutting-edge of health disparities and environmental health research and seeks to answer critical scientific as well as policy-relevant questions for improving the health of vulnerable populations who often face disproportionate and elevated exposures to multiple chemical and non-chemical stressors.