The Impact of Maternal and Paternal Preconception Perfluoroalkyl Substance (PFAS) Exposure on Reproductive and Perinatal Outcomes

全氟和多氟烷基物质(PFAS)是普遍存在的环境毒物，与 不利的健康后果，包括癌症和甲状腺疾病。全氟辛烷磺酸暴露于负面影响的可能性 对人类健康的影响在科学、政府和公共领域引起了极大的关注。全氟辛烷磺酸 用于许多消费品，包括不粘厨具、纺织品和食品包装。 重要的是，这些化学品在环境中持续存在，并具有很长的消除半衰期(~2至8年)。 人体，导致近乎普遍的暴露(一些全氟化铝已在超过 占美国人口的99%)。虽然有限的人类研究和动物模型的证据表明PFAS 暴露于不良生殖和妊娠后果，包括不孕、流产、早产、 而且出生体重低，知识仍然稀缺，特别是对于较新的全氟辛烷磺酸和全氟辛烷磺酸混合物。此外， 检查围产儿结局的研究，如早产和低出生体重，测量了血清/血浆 怀孕期间的浓度，这可能会导致与怀孕有关的生理变化造成混淆。 因此，有必要进行研究，以便在受孕前测量全氟辛烷磺酸的暴露程度。为了更好地 确定全氟辛烷磺酸暴露对生殖和妊娠结局的影响，因为环境 暴露也可能影响男性生殖成功，我们提出了一项创新的研究，以测量血清 受孕前男性和女性体内相关全氟辛烷磺酸分析物的浓度。我们将利用 环境与生殖健康(地球)研究(ES009718)，前瞻性先入为主的队列 夫妇从生育诊所招募，并在分娩过程中进行跟踪。这项提案的目的是确定 母亲和父亲怀孕前血清PFAS浓度(单独和作为PFAS)的程度 混合物)与：目的1)受精、植入和精液质量的生殖结果 参数；目的2)妊娠丢失和活产的妊娠结局；和目的3)出生结局 出生体重和胎龄。创新包括评估先入为主，暴露于新兴和 新型全氟辛烷磺酸及其混合物在夫妇中的应用及早期生殖和妊娠结局的调查 以前没有被研究过的。拟议的研究具有很高的时间和成本效益，因为我们将 可获得834名未分娩妇女和435名男子(435对夫妇)的存档生物标本和临床数据。我们 将额外招聘225名未分娩妇女和180名男性伴侣，以将统计权力增加到总数 615对情侣。我们的团队包括男性和女性生殖和环境流行病学方面的专业知识， 全氟辛烷磺酸暴露评估，以及先进的生物统计和混合物分析方法。建议进行的研究 通过检查母亲和父亲的全氟化验，将具有重要的科学和公共卫生影响 关于生殖、怀孕和出生结果的暴露，为循证提供急需的数据 减少全氟辛烷磺酸暴露和危害的政策。

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental toxicants that are associated with adverse health outcomes including cancer and thyroid disease. The potential for PFAS exposures to negatively influence human health has generated significant concerns in scientific, governmental and public realms. PFAS are used in numerous consumer products, including nonstick cookware, textiles, and food packaging. Importantly, these chemicals persist in the environment and have long elimination half-lives (~2 to 8 years) in the human body, leading to near-universal exposure (some PFAS have been detected in the serum of more than 99% of the U.S. population). While limited human studies and evidence from animal models implicate PFAS exposures in adverse reproductive and pregnancy outcomes including infertility, pregnancy loss, preterm birth, and low birthweight, knowledge remains scarce, particularly for newer PFAS and PFAS mixtures. Further, studies that examined perinatal outcomes such as preterm birth and low birthweight measured serum/plasma concentrations during pregnancy, which may result in confounding by pregnancy-related physiologic changes. Hence, there is a significant need for studies designed to measure PFAS exposure before conception. To better define the impact of PFAS exposure on reproductive and pregnancy outcomes, and because environmental exposures may also affect male reproductive success, we propose an innovative study to measure serum concentrations of relevant PFAS analytes in both men and women before conception. We will leverage the Environment and Reproductive Health (EARTH) Study (ES009718), a prospective preconception cohort of couples recruited from a fertility clinic and followed through delivery. The aims of this proposal are to determine the extent to which maternal and paternal preconception serum PFAS concentrations (individually and as PFAS mixtures) are associated with: AIM 1) reproductive outcomes of fertilization, implantation, and semen quality parameters; AIM 2) pregnancy outcomes of pregnancy loss and live birth; and AIM 3) birth outcomes of birthweight and gestational age. Innovations include the assessment preconception exposure to emerging and new PFAS and their mixtures in couples and the investigation of early reproductive and pregnancy outcomes that have not been previously studied. The proposed study is highly time- and cost-efficient, as we will have archived biospecimens and clinical data available for 834 nulliparous women and 435 men (435 couples). We will recruit an additional 225 nulliparous women and 180 male partners to increase statistical power to a total of 615 couples. Our team includes expertise in male and female reproductive and environmental epidemiology, PFAS exposure assessment, and advanced biostatistical and mixtures analysis methods. The proposed study will have important scientific and public health implications by examining both maternal and paternal PFAS exposure on reproductive, pregnancy, and birth outcomes, providing much needed data for evidence-based policy to reduce PFAS exposure and harm.