In utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate promotes local adipose and systemic inflammation in adult male offspring

被引:74
作者
Campioli, E. [1 ,2 ]
Martinez-Arguelles, D. B. [1 ,2 ]
Papadopoulos, V. [1 ,2 ,3 ,4 ]
机构
[1] McGill Univ, Res Inst, Ctr Hlth, Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada
[2] McGill Univ, Dept Med, Montreal, PQ H3G 1A4, Canada
[3] McGill Univ, Dept Biochem, Montreal, PQ H3G 1A4, Canada
[4] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1A4, Canada
基金
加拿大健康研究院;
关键词
RENIN-ANGIOTENSIN SYSTEM; C-REACTIVE PROTEIN; DI(2-ETHYLHEXYL) PHTHALATE; TNF-ALPHA; MONO-(2-ETHYLHEXYL) PHTHALATE; MONO(2-ETHYLHEXYL) PHTHALATE; LACTATIONAL EXPOSURE; INSULIN-RESISTANCE; HUMAN ADIPOCYTES; URINARY LEVELS;
D O I
10.1038/nutd.2014.13
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND: Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer used to increase the flexibility of polyvinyl chloride. DEHP and its active metabolite mono-(2-ethylhexyl) phthalate are detected in many biological fluids during fetal and postnatal life. In rodent models, in utero DEHP exposure has been shown to alter sexual organ development, decrease testosterone and aldosterone production, increase body and epididymal adipose tissue weight, and raise serum lipids and glucose levels in male offspring. OBJECTIVES: The objective of this study is to characterize the effects of in utero DEHP exposure on adipose tissue development and function in male offspring. METHODS: Sprague-Dawley pregnant dams were gavaged 1, 20, 50 or 300mg DEHP per kg per day from gestational day 14 until birth. RESULTS: Global gene expression analyses of postnatal day 60 male offspring that were exposed in utero to 300mg DEHP per kg per day revealed increased expression of immune response and inflammation markers, and increased expression of differentiation pathway genes in the epididymal whole-adipose tissue and isolated stromal vascular fraction. C-reactive protein and tumor necrosis factor (TNF) serum levels were increased in the 300mg DEHP in utero-exposed offspring. TNF levels in adipose tissue homogenates were increased in the 50 and 300mg DEHP in utero-exposed offspring. Immunofluorescence studies revealed focal macrophage infiltration in whole-adipose tissue confirmed by increased CD163 tissue content. CONCLUSIONS: In utero DEHP exposure promotes local adipose tissue inflammation and chronic low-grade systemic inflammation. Moreover, evidence is presented, suggesting that DEHP increases the differentiation capacity of the pre-adipocytes of male offspring without affecting total body weight.
引用
收藏
页码:e115 / e115
页数:10
相关论文
共 62 条
[1]   Harmonizing the Metabolic Syndrome A Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity [J].
Alberti, K. G. M. M. ;
Eckel, Robert H. ;
Grundy, Scott M. ;
Zimmet, Paul Z. ;
Cleeman, James I. ;
Donato, Karen A. ;
Fruchart, Jean-Charles ;
James, W. Philip T. ;
Loria, Catherine M. ;
Smith, Sidney C., Jr. .
CIRCULATION, 2009, 120 (16) :1640-1645
[2]   DEPRESSED PLASMA TESTOSTERONE AND FRACTIONAL BINDING OF TESTOSTERONE IN OBESE MALES [J].
AMATRUDA, JM ;
HARMAN, SM ;
POURMOTABBED, G ;
LOCKWOOD, DH .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1978, 47 (02) :268-271
[4]   Maternal in utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate affects the blood pressure of adult male offspring [J].
Arguelles, D. B. Martinez ;
McIntosh, M. ;
Rohlicek, C. V. ;
Culty, M. ;
Zirkin, B. R. ;
Papadopoulos, V. .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 2013, 266 (01) :95-100
[5]   Mono-2-ethylhexylphthalate (MEHP) induces TNF-α release and macrophage differentiation through different signalling pathways in RAW264.7 cells [J].
Bolling, Anette Kocbach ;
Ovrevik, Johan ;
Samuelsen, Jan Tore ;
Holme, Jorn A. ;
Rakkestad, Kirsten E. ;
Mathisen, Gro H. ;
Paulsen, Ragnhild E. ;
Korsnes, Monica Suarez ;
Becher, Rune .
TOXICOLOGY LETTERS, 2012, 209 (01) :43-50
[6]   Hormesis: The dose-response revolution [J].
Calabrese, EJ ;
Baldwin, LA .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 2003, 43 :175-197
[7]   Release of C-reactive protein in response to inflammatory cytokines by human adipocytes: Linking obesity to vascular inflammation [J].
Calabro, P ;
Chang, DW ;
Willerson, JT ;
Yeh, ETH .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2005, 46 (06) :1112-1113
[8]   Automated solid phase extraction and quantitative analysis of human milk for 13 phthalate metabolites [J].
Calafat, AM ;
Slakman, AR ;
Silva, MJ ;
Herbert, AR ;
Needham, LL .
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2004, 805 (01) :49-56
[9]   The Endocrine Disruptor Mono-(2-Ethylhexyl) Phthalate Affects the Differentiation of Human Liposarcoma Cells (SW 872) [J].
Campioli, Enrico ;
Batarseh, Amani ;
Li, Jiehan ;
Papadopoulos, Vassilios .
PLOS ONE, 2011, 6 (12)
[10]   REGULATED EXPRESSION OF 3 C/EBP ISOFORMS DURING ADIPOSE CONVERSION OF 3T3-L1 CELLS [J].
CAO, ZD ;
UMEK, RM ;
MCKNIGHT, SL .
GENES & DEVELOPMENT, 1991, 5 (09) :1538-1552