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

描述（由申请人提供） 该K99/R 00职业发展计划的目标是启动一项关于内分泌干扰化学品（EDCs）的生殖和环境流行病学的独立研究计划，其中包括评估可能影响重叠生物途径的健康社会决定因素。为了实现这一目标，候选人将通过生殖生物学，社会流行病学/压力科学和环境流行病学方法的教学和实践培训来提高她在环境健康科学方面的专业知识。这种专业培训将使她能够实现成为一名独立的学术调查员的长期目标，并就环境和社会因素对生殖健康的累积影响提供新的见解。 候选人研究计划的主要目标是评估多溴二苯醚和心理社会压力对社会经济和种族多样的孕妇人群中甲状腺激素紊乱和随后的围产期结果的独立影响。这项工作特别具有创新性，因为多溴二苯醚和心理社会压力都会影响甲状腺系统，这表明它们之间存在生物学上的相互作用;然而，从未在人类研究中同时对这两种接触进行过研究。 在K99指导阶段，在Tracey Woodruff博士的主要指导下，候选人将使用创新措施来描述与生物相关的多溴二苯醚接触和心理社会压力及其对甲状腺激素干扰的影响。将使用多溴联苯醚同系物及其羟基化代谢物（羟基多溴联苯醚）评估多溴联苯醚的接触情况。心理压力将通过压力和端粒长度的主观测量进行评估，端粒长度是受心理压力影响的细胞衰老的生物标志物。 在独立阶段，候选人将运用这些知识调查多溴二苯醚和心理社会压力对不良围产期结果的独立影响，如妊娠期高血压、早产和出生体重不足，并评估这些影响是否通过甲状腺系统介导。这项工作的整合将使候选人能够制定必要的方法和生物学框架，以检查未来R 01研究中环境和心理社会因素对围产期结局的综合和潜在协同作用。 候选人有能力在加州大学弗朗西斯科分校实现这些目标，这是一个备受尊敬的研究机构，拥有强大的环境生殖健康计划，具有心理社会压力专业知识的世界知名教师，以及广泛的生物医学基础设施。 在生殖科学，环境流行病学，健康差异，压力科学和生物统计学的主要导师和共同导师将指导候选人学习完成本提案中规定的目标所需的方法的过程。该项目代表了健康差异和环境健康研究的前沿，旨在回答关键的科学问题以及与政策相关的问题，以改善弱势群体的健康，这些群体往往面临不成比例和更高的多种化学品和非化学品压力。 公共卫生相关性：该项目的目标是准备Ami Zota博士过渡到环境健康科学的独立学术调查员，专注于怀孕期间内分泌干扰化学品（EDCs）的后果以及可能影响重叠生物途径的社会因素。 她将进行流行病学分析，以调查多溴二苯醚（PBDE）阻燃剂和心理社会压力对围产期结局的影响，并评估这些影响是否由甲状腺系统介导。 这项工作的结果将改善妊娠结果，并为公共卫生政策提供信息，特别是针对弱势亚群体，他们经常面临化学品和非化学品压力因素的增加。

DESCRIPTION (provided by applicant) The goal of this 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, the candidate will enhance her 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 her to achieve her 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 the candidate's 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, the candidate 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, the candidate 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 the candidate 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. The candidate is 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. The primary mentor and co-mentors in reproductive sciences, environmental epidemiology, health disparities, stress science, and biostatistics will guide the process whereby the candidate 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. Public Health Relevance: The goal of this project is to prepare Dr. Ami Zota to transition to a position as an independent academic investigator in environmental health sciences focusing on the consequence of endocrine-disrupting chemicals (EDCs) during pregnancy and social factors that may affect overlapping biologic pathways. She will conduct epidemiologic analyses to investigate the effects of polybrominated diphenyl ether (PBDE) flame retardants and psychosocial stress on perinatal outcomes and assess whether these effects are mediated by the thyroid system. Results from this work will improve pregnancy outcomes and inform public health policy, particularly for vulnerable subpopulations, who often encounter elevated exposures to chemical and non-chemical stressors.