Maternal Adrenalectomy Abrogates the Effect of Fetal Alcohol Exposure on the Interleukin-1β-Induced Febrile Response: Gender Differences

Abstract

Fetal alcohol exposure (FAE) has been shown to blunt the febrile component of the primary host-defense response to infection induced experimentally by systemic administration of interleukin (IL)-1β. Given that maternal adrenalectomy (ADX) can prevent various postnatal effects of FAE, the present experiments were designed to determine whether maternal ADX would prevent the blunted IL-1β-induced febrile response of fetal alcohol-exposed offspring and whether the effects of maternal ADX would be gender related. Timed-pregnant rats underwent ADX or were sham-operated on gestation day (GD) 7, or remained intact (without any surgery), and were fed ethanol-containing (E) or pair-fed (PF) liquid diets or normal (N) rat chow and water from GD 8 to GD 21. As adults, male and female E, PF and N offspring were injected with saline on day 1 and with IL-1β (2 µg/kg, i.p.) on day 2 at 09.00 h and the body temperature was recorded biotelemetrically for 8.5 h. IL-1β produced significantly lower febrile responses in female than in male offspring of intact dams, irrespective of prenatal diet. Furthermore, prenatal surgical stress differentially affected the IL-1β-induced febrile response of male and female normally fed offspring. Additionally, in both male and female offspring of intact dams, FAE significantly attenuated the IL-1β-induced febrile response. In males, FAE also attenuated the febrile response in the offspring of maternal sham-operated dams, and this effect was completely reversed by maternal ADX. In females, both maternal sham surgery and ADX reversed the effect of FAE on the febrile response. These findings suggest that maternal adrenal mediators are essential for the long-term effect of FAE on the febrile response in male offspring. In females, early prenatal surgical stress is sufficient to reverse the effects of FAE, possibly via adrenal-independent mechanisms that affect the thermoregulatory system.

Prenatal ethanol exposure enhances NMDAR‐dependent long‐term potentiation in the adolescent female dentate gyrus

“…Ethanol can stimulate maternal HPA activity (Wilkins and Gorelick, 1986;Spencer and McEwen, 1990;Wand and Dobs, 1991;Rivier, 1996) and maternal adrenalectomy can rescue some of the behavioral deficits induced by PNEE (Slone and Redei, 2002;Taylor et al, 2002;Wilcoxon et al, 2003). Indeed, CORT can directly mediate the deleterious effects of maternal ethanol consumption on offspring growth (Tritt et al, 1993).…”

Prenatal Alcohol Exposure and Fetal Programming: Effects on Neuroendocrine and Immune Function

“…It has been suggested that a decreased response of central thermoregulatory systems to IL-1b caused by decreased hypothalamic IL-1b production after LPS administration may mediate this blunted fever response in ethanol-exposed animals, possibly through an impaired release of endogenous pyrogens (92)(93)(94). Interestingly, both maternal adrenalectomy and sham surgery abrogate the effect of ethanol on IL-1b-induced febrile responses in female offspring, but only adrenalectomy has an effect on male offspring, suggesting that maternal adrenal mediators play an important role in the blunted febrile response of males but that nonadrenal mediators participate in modulation of thermoregulatory systems in females (95,96).…”

Novel role of adrenergic neurons in the brain stem in mediating the hypothalamic–pituitary axis hyperactivity caused by prenatal alcohol exposure

“…Of the varying effects of fetal alcohol exposure (FAE), studies conducted in recent decades have identified less pronounced changes that occur in the brain without presenting the classic dismorphology that occurs with FAS. These changes range from alterations in neuroendocrine, immune and behavioural functions (Taylor et al, 1984;Angelogianni and Gianoulakis, 1989;Halasz et al, 1993;Nagahara and Handa, 1995;Yirmiya et al, 1996;Taylor et al, 2002) to impairment of the hippocampus affecting adult neurogenesis (Choi et al, 2005) and learning and memory (Girard et al, 2000;Dursun et al, 2006). For many years, our laboratory has focused on one of the most prevalent neuroendocrine dysfunctions caused by prenatal alcohol exposure, namely the hyperresponsiveness of the hypothalamic-pituitary-adrenal (HPA) axis, which results in exaggerated adrenocorticotrophic hormone (ACTH) release in response to a variety of stressors {see for example (Taylor et al, 1982;Nelson et al, 1986;Weinberg, 1988;Lee et al, 1990;Weinberg, 1992a, b;Ogilvie and Rivier, 1997;Yirmiya et al, 1998)}.…”