title: Prenatal phthalate exposure: epigenetic changes leading to lifelong impact on steroid formation.
abstract: Endocrine disruptors (ED) are environmental pollutants that mimic endogenous hormonal signals. Exposure to EDs during fetal and early life is a public health concern because these are periods characterized by high cellular plasticity that influence the physiology and development of disease later in life. Phthalates are plasticizers used in the industry to manufacture polyvinyl chloride products and several consumer products. Di(2-ethylhexyl) phthalate (DEHP) is one of the most produced plasticizers; it is ubiquitously found contaminating the environment, and has been shown to be an ED. Human exposure to phthalates starts during fetal development and continues after birth through contact of the newborn with the environment and contaminated food sources. We used a rat model in which pregnant dams are gavaged with DEHP from gestational day 14 until birth to study the long-term effects of DEHP. This window of fetal exposure results in decreased circulating testosterone and aldosterone levels in adult male offspring and estradiol in the female. The observed steroid changes are likely of an epigenetic origin as DEHP is rapidly cleared after birth. Here, we review the long-term effects of fetal exposure to DEHP with a focus on the molecular and epigenetic changes, including DNA methylation, which may mediate long-term endocrine dysfunction.
authors.affiliation: The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada.|Department of Medicine, McGill University, Montreal, QC, Canada.
authors.forename: D B
authors.initials: DB
authors.lastname: Martinez-Arguelles
authors.affiliation: The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada.|Department of Medicine, McGill University, Montreal, QC, Canada.|Department of Biochemistry, McGill University, Montreal, QC, Canada.|Department of Pharmacology & Therapeutics, McGill University, Montreal, Quebec, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Papadopoulos
mesh_terms: D000450:Aldosterone / Q000097:blood*; D000818:Animals; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D004958:Estradiol / Q000097:blood*; D005260:Female; D008297:Male; D010968:Plasticizers / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013739:Testosterone / Q000097:blood*
chemical_list: D010968:Plasticizers; D013739:Testosterone; D000450:Aldosterone; D004958:Estradiol; D004051:Diethylhexyl Phthalate
keywords: Leydig cell; adrenal; aldosterone; axis; epigenetics; glomerulosa; steroids; testosterone