Prenatal cytokine exposure results in obesity and gender-specific programming

Prenatal events appear to program hormonal homeostasis, contributing to the development of somatic disorders at an adult age. The aim of this study wa s to examine whether maternal exposure to cytokines or to dexamethasone (Dx m) 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 eithe r human interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-alpha) or with Dxm. Control dams were injected with vehicle. All exposed offspring de veloped increased body weight (P < 0.05-0.001), apparently due to an increa se of 30-40% in adipose tissue weight (P < 0.05-0.01). Corticosterone respo nse 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), wh ereas basal insulin was elevated in the TNF-alpha group (P < 0.01). In fema le rats, plasma testosterone levels were higher in all exposed groups compa red with controls (P < 0.01-0.001), with the exception of Dxm-exposed offsp ring. 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 Dx m leads to increased fat depots in both genders. In females, cytokine expos ure was followed by a state of hyperandrogenicity. The results suggest that prenatal exposure to cytokines or Dxm can induce gender-specific programmi ng of neuroendocrine regulation with consequences in adult life.