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Am J Physiol Endocrinol Metab 281: E326-E334, 2001;
0193-1849/01 $5.00
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Vol. 281, Issue 2, E326-E334, August 2001

Prenatal cytokine exposure results in obesity and gender-specific programming

Jovanna Dahlgren1, Cecilia Nilsson2,5, Eva Jennische3, Hoi-Por Ho4, Elias Eriksson4, Aimon Niklasson1, Per Björntorp2,5, Kerstin Albertsson Wikland1, and Agneta Holmäng2,5

1 Göteborg Pediatric Growth Research Center, Institute for the Health of Women and Children and Departments of 2 Heart and Lung Diseases, 3 Histology, and 4 Pharmacology, and the 5 Wallenberg Laboratory, University of Göteborg, S-416 85 Goteborg, Sweden

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.

glucocorticoids; intrauterine exposure; hypothalamic-pituitary-adrenal axis; hypothalamic-pituitary-gonadal axis


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