Placental adaptive mechanisms to environmental exposures.

胎盘对环境暴露的适应机制。

• 批准号: 10378855
• 负责人: Almudena Veiga-Lopez
• 金额: $ 7.44万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-11-19 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10378855
• 关键词: Adult; Affect; Affinity; Animal Model; Cardiometabolic Disease; Cell Line; Cells; Chemicals; Communication; Data; Development; Disease; Endocrine Disruptors; Endocrine system; Environmental Exposure; Equilibrium; Exposure to; Fetal Development; Fetal Growth Retardation; Functional disorder; Health; Human; In Vitro; Industrialization; Long-Term Effects; Mediating; Metabolic Diseases; Molecular; Mothers; Outcome; Pathway interactions; Personal Satisfaction; Phenotype; Placenta; Policies; Pregnancy; Progesterone Receptors; Regulation; Risk; Sheep; Steroids; Testing; bisphenol A; cardiometabolism; chemical substitution; consumer product; cytotrophoblast; fetal; in vivo; in vivo Model; manufacturing process; mother nutrition; novel; prenatal exposure; trophoblast

ABSTRACT The placenta is the gateway between the mother and the developing fetus. Placental dysfunction can impair fetal growth and induce long-term effects in the progeny, including increased risk for metabolic diseases. The delicate balance of feto-maternal communication / exchange can be affected by a number of factors including maternal diet and diseases and / or exposure to endocrine disrupting compounds (EDCs). EDCs are synthetic or natural chemicals that interfere with the normal function of the endocrine system with some EDCs having steroidal activity. Fetal exposure to such EDCs can pose a threat to adult well-being. Current policy regulations are limiting the use of one of such EDCs, bisphenol A (BPA), in the manufacture process of consumer products. Emergence of new, untested, industrial chemical substitutes such as bisphenol S (BPS), an EDC with very distinct steroid affinities compared to BPA, are on the rise. Understanding the health risks posed by emerging EDC exposures is critical. Our preliminary studies using sheep as an in vivo model and in vitro studies using human cytotrophoblasts demonstrate that BPS exposure alters placental trophoblast function. BPA does not lead to a similar placental phenotype, highlighting critical and unexplored differences among bisphenolic EDCs. Our preliminary data suggest that BPS mediates its action via the progesterone receptor pathway. In our animal model, gestational BPS exposure also impacts fetal size and leads to cardio-metabolic disruptions. Studies described in this proposal will capitalize on a unique animal model of feto-maternal communication, primary trophoblast cells and trophoblast cell lines to test a novel hypothesis for the developmental origin of cardio-metabolic disorders with specific emphasis on understanding the molecular mechanisms whereby BPS compromises trophoblast function placental function and long-term cardio- metabolic effects on the progeny.

摘要