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（由申请人提供）：本申请的目的是测试产前性类固醇激素在妊娠早期邻苯二甲酸盐（合成内分泌干扰化学物质）暴露和新生儿肛门生殖器距离（AGD）之间的作用。初级泌尿生殖系统发育和规划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为敏感。AGD发生在这个编程窗口期，是一种激素敏感的生殖毒性终点，通常用于动物研究。AGD的改变与新生儿临床显著的生殖道异常、生育能力下降和生命后期的精液参数异常有关。一般人群广泛接触邻苯二甲酸盐，可影响妊娠期间的激素浓度和功能，导致动物和人类激素介导的不良后果，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来确定怀孕早期邻苯二甲酸盐暴露与性类固醇激素浓度之间的关系。它还将研究早孕性类固醇激素与男女婴儿AGD之间的关系。在胎儿泌尿生殖系统编程窗口期间，邻苯二甲酸盐暴露与性类固醇激素浓度和新生儿AGD之间的关系将是第一个研究。研究结果对了解邻苯二甲酸盐影响生殖发育的生物学途径以及弱势群体邻苯二甲酸盐暴露政策具有重要意义。