title: Gestational exposure to di(2-ethylhexyl) phthalate (DEHP) impairs pancreatic β-cell function in F1 rat offspring.
abstract: Di(2-ethylhexyl) phthalate, a distinctive endocrine-disrupting chemical (EDC), is widely used as plasticizer. Gestational exposure to EDCs like DEHP may program a permanent diabetes disposition. We investigated whether gestational DEHP exposure disrupts glucose homeostasis in the rat F1 offspring as a result of early impairment in the functions of endocrine pancreas. Pregnant Wistar rats were administered with DEHP (1, 10 and 100mgkg-(1)day-(1)) or olive oil from gestational day 9-21 by oral gavage. DEHP-exposed offspring exhibited elevated blood glucose, impaired insulin, glucose tolerance, glucose-stimulated insulin secretion and decreased pancreatic insulin content at postnatal day 60 (PND60). Global DNA methylation level was increased while the expression of genes involved in the development and function of β-cells were down regulated in islets in DEHP exposed groups. Gestational exposure to DEHP favours β-cell dysfunction and the whole body glucometabolic abnormalities in the F1 offspring by down regulating the expression of critical genes. Further, DEHP-induced epigenetic changes in genes involved in β-cell development and function appear to play a significant role.
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai 600 113, India.
authors.forename: P
authors.initials: P
authors.lastname: Rajesh
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai 600 113, India. Electronic address: kbala82@hotmail.com.
authors.forename: K
authors.initials: K
authors.lastname: Balasubramanian
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005865:Gestational Age; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018811:Maternal Exposure; D010968:Plasticizers / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D052244:Endocrine Disruptors; D007328:Insulin; D010968:Plasticizers; D012333:RNA, Messenger; D004051:Diethylhexyl Phthalate
keywords: Di(2-ethylhexyl) phthalate; Endocrine disruptor; Insulin; MafA; β-cell