Prenatal Environmental Exposure and Reproductive Hormone Concentrations (PERCH)

产前环境暴露和生殖激素浓度 (PERCH)

• 批准号: 8680767
• 负责人: Sheela Sathyanarayana
• 金额: $ 25.21万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8680767
• 关键词: Address; Adult; Affect; Animals; Biological; Birth; Chemical Exposure; Clinical; Congenital adrenal hyperplasia; Cryptorchidism; Data; Decision Making; Development; Dibutyl Phthalate; Endocrine Disruptors; Environment; Environmental Risk Factor; Estradiol; Estriol; Exposure to; Female; Fertility; Fetus; First Pregnancy Trimester; General Population; Genital system; Genitourinary system; Goals; Gonadal Steroid Hormones; Grant; Hormones; Human; Hypospadias; Infant; Infant Development; Life; Link; Measures; Mediating; National Institute of Environmental Health Sciences; Newborn Infant; Outcome; Ovarian Granulosa Cell; Pathway interactions; Play; Policies; Predisposition; Pregnancy; Pregnant Women; Production; Program Development; Rodent; Role; Sampling; Science; Seminal fluid; Specimen; Testing; Testosterone; Time; Toxic effect; Translations; Variant; Vulnerable Populations; clinically significant; fetal; male; phthalates; policy implication; prenatal; prenatal environmental exposure; programs; public health relevance; reproductive; reproductive development; reproductive hormone; urinary

DESCRIPTION (provided by applicant): The aim of this application is to test the role of prenatal sex steroid hormones as the link between first trimester phthalate (synthetic endocrine disrupting chemical) exposure and newborn anogenital distance (AGD). Primary genitourinary development and programming occurs in the first 5-18 weeks of human gestation when the developing fetus is extremely sensitive to changes in sex steroid hormone concentrations that direct genital differentiation and development. AGD develops during this programming window and is a hormone sensitive reproductive toxicity endpoint commonly used in animal studies. Changes in AGD are associated with clinically significant newborn reproductive tract abnormalities and reduced fertility and abnormal semen parameters later in life. The general population is widely exposed to phthalates which can affect hormone concentrations and function during gestation leading to adverse hormone-mediated outcomes in animal and humans, including changes in AGD. The Prenatal Environmental Exposure and Reproductive Hormone Concentrations (PERCH) study will use data and samples from The Infant Development and the Environment Study to determine the relationship between phthalate exposures and sex steroid hormone concentrations in early pregnancy. It will also examine the relationship between early pregnancy sex steroid hormones and AGD in male and female infants. PERCH will be the first study to examine phthalate exposures during the fetal genitourinary programming window in relation to sex steroid hormone concentrations and newborn AGD. Results have important implications for understanding the biological pathway in which phthalates may impact reproductive development as well as for policy surrounding phthalate exposures in vulnerable populations.

描述（由申请方提供）：本申请旨在检测产前性类固醇激素作为妊娠早期邻苯二甲酸酯（合成内分泌干扰化学品）暴露与新生儿肛门生殖器距离（AGD）之间联系的作用。原发性泌尿生殖系统发育和编程发生在人类妊娠的前5-18周，此时发育中的胎儿对指导生殖器分化和发育的性类固醇激素浓度的变化极其敏感。AGD在该程控窗口期间发展，是动物研究中常用的激素敏感性生殖毒性终点。AGD的变化与临床上显著的新生儿生殖道异常、生育力降低和生命后期精液参数异常相关。一般人群广泛暴露于邻苯二甲酸酯，这可能会影响妊娠期间的激素浓度和功能，导致动物和人类的不良妊娠介导的结果，包括AGD的变化。产前环境暴露和生殖激素浓度（PERCH）研究将使用来自婴儿发育和环境研究的数据和样本，以确定妊娠早期邻苯二甲酸酯暴露与性类固醇激素浓度之间的关系。它还将研究早期妊娠性类固醇激素和男女婴儿AGD之间的关系。PERCH将是第一项检查胎儿泌尿生殖道编程窗口期间邻苯二甲酸酯暴露与性类固醇激素浓度和新生儿AGD相关的研究。研究结果对于了解邻苯二甲酸酯可能影响生殖发育的生物学途径以及弱势人群邻苯二甲酸酯暴露的政策具有重要意义。