title: Maternal exposure to di-(2-ethylhexyl) phthalate exposure deregulates blood pressure, adiposity, cholesterol metabolism and social interaction in mouse offspring.
abstract: Long-term exposure to di-(2-ethylhexyl) phthalate (DEHP) is highly associated with carcinogenicity, fetotoxicity, psychological disorders and metabolic diseases, but the detrimental effects and mechanisms are not fully understood. We investigated the effect of exposing mouse mothers to DEHP, and the underlying mechanism, on blood pressure, obesity and cholesterol metabolism as well as psychological and learning behaviors in offspring. Tail-cuff plethysmography was used for blood pressure measurement; Western blot used was for phosphorylation and expression of protein; hematoxylin and eosin staining, Nissl staining and Golgi staining were used for histological examination. The serum levels of cholesterol, triglycerides and glucose were measured by blood biochemical analysis. Hepatic cholesterol and triglyceride levels were assessed by colorimetric assay kits. Offspring behaviors were evaluated by open-field activity, elevated plus maze, social preference test and Morris water maze. Maternal DEHP exposure deregulated the phosphorylation of endothelial nitric oxide synthase and upregulated angiotensin type 1 receptor in offspring, which led to increased blood pressure. It led to obesity in offspring by increasing the size of adipocytes in white adipose tissue and number of adipocytes in brown adipose tissue. It increased the serum level of cholesterol in offspring by decreasing the hepatic capacity for cholesterol clearance. The impaired social interaction ability induced by maternal DEHP exposure might be due to abnormal neuronal development. Collectively, our findings provide new evidence that maternal exposure to DEHP has a lasting effect on the physiological functions of the vascular system, adipose tissue and nerve system in offspring.
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan.
authors.forename: Kuan-I
authors.initials: KI
authors.lastname: Lee
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan.
authors.forename: Chin-Wei
authors.initials: CW
authors.lastname: Chiang
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan.|Brain Research Center, National Yang-Ming University, Taipei, 11221, Taiwan.
authors.forename: Hui-Ching
authors.initials: HC
authors.lastname: Lin
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan.
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Zhao
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 11221, Taiwan.
authors.forename: Cheng-Ta
authors.initials: CT
authors.lastname: Li
authors.affiliation: Cardiovascular Division, Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan.
authors.forename: Song-Kun
authors.initials: SK
authors.lastname: Shyue
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan. tslee@ym.edu.tw.|Brain Research Center, National Yang-Ming University, Taipei, 11221, Taiwan. tslee@ym.edu.tw.|Genome Research Center, National Yang-Ming University, Taipei, 11221, Taiwan. tslee@ym.edu.tw.
authors.forename: Tzong-Shyuan
authors.initials: TS
authors.lastname: Lee
mesh_terms: D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood*; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D005260:Female; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D018811:Maternal Exposure; D018782:Maze Learning / Q000187:drug effects; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012919:Social Behavior
chemical_list: D015415:Biomarkers; D002784:Cholesterol; D004051:Diethylhexyl Phthalate
keywords: Adiposity; Blood pressure; Cholesterol metabolism; Di-(2-ethylhexyl) phthalate; Offspring; Social interaction