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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-
(TNF-) 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- 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- 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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