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Prenatal cytokine exposure results in obesity and gender-specific programming.

Journal article
Authors Jovanna Dahlgren
Cecilia Nilsson
Eva Jennische
Hoi-Por Ho
Elias Eriksson
Aimon Niklasson
Per Björntorp
Kerstin Albertsson-Wikland
Agneta Holmäng
Published in American journal of physiology. Endocrinology and metabolism
Volume 281
Issue 2
Pages E326-34
ISSN 0193-1849
Publication year 2001
Published at Cardiovascular Institute
Institute of Anatomy and Cell Biology
Institute of Physiology and Pharmacology, Dept of Pharmacology
Institute for the Health of Women and Children, Dept of Paediatrics
Pages E326-34
Language en
Links www.ncbi.nlm.nih.gov/entrez/query.f...
Keywords Adipose Tissue, drug effects, Animals, Body Weight, drug effects, Corticosterone, metabolism, Cytokines, administration & dosage, Dexamethasone, administration & dosage, Drug Administration Schedule, Exercise Test, drug effects, Female, Glucocorticoids, administration & dosage, Insulin, pharmacology, Interleukin-6, administration & dosage, Male, Motor Activity, drug effects, Neurosecretory Systems, drug effects, physiology, Obesity, chemically induced, Pregnancy, Prenatal Exposure Delayed Effects, Rats, Sex Factors, Testosterone, blood, Tumor Necrosis Factor-alpha, administration & dosage
Subject categories Pharmacology and Toxicology

Abstract

Prenatal events appear to program hormonal homeostasis, contributing to the development of somatic disorders at an adult age. The aim of this study was to examine whether maternal exposure to cytokines or to dexamethasone (Dxm) would be followed by hormonal consequences in the offspring at adult age. Pregnant rats were injected on days 8, 10, and 12 of gestation with either human interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-alpha) or with Dxm. Control dams were injected with vehicle. All exposed offspring developed increased body weight (P < 0.05--0.001), apparently due to an increase of 30--40% in adipose tissue weight (P < 0.05--0.01). Corticosterone response to stress was increased in the IL-6 group (P < 0.05-0.01). Dxm-treated male rats exhibited blunted Dexamethasone suppression test results. In male rats, insulin sensitivity was decreased after IL-6 exposure (P < 0.01), whereas basal insulin was elevated in the TNF-alpha group (P < 0.01). In female rats, plasma testosterone levels were higher in all exposed groups compared with controls (P < 0.01--0.001), with the exception of Dxm-exposed offspring. Males in the TNF-alpha group showed decreased locomotor activity (P < 0.05), and females in the IL-6 group showed increased locomotor activity (P < 0.05). These results indicate that prenatal exposure to cytokines or Dxm leads to increased fat depots in both genders. In females, cytokine exposure was followed by a state of hyperandrogenicity. The results suggest that prenatal exposure to cytokines or Dxm can induce gender-specific programming of neuroendocrine regulation with consequences in adult life.

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