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Title: Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups aftermore » stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine-induced reproductive and developmental toxicities in F1 have hereditary effect. • Caffeine-induced programming of HPA axis in F2 has gender and parental differences.« less
Authors:
 [1] ;  [2] ; ; ; ; ;  [1] ; ;  [1] ;  [2] ;  [3] ;  [4] ;  [1] ;  [2]
  1. Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China)
  2. (China)
  3. Department of Epidemiology and Health Statistics, Public Health School of Wuhan University, Wuhan 430071 (China)
  4. Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China)
Publication Date:
OSTI Identifier:
22285590
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 274; Journal Issue: 3; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BLOOD; CAFFEINE; CHOLESTEROL; CORTICOSTERONE; GLUCOSE; LIPOPROTEINS; METABOLISM; PHENOTYPE; RATS; RECEPTORS; TOXICITY; TRIGLYCERIDES