RESUMEN
Animals prenatally exposed to ethanol typically exhibit hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stressors. In contrast to previous studies that have investigated effects of prenatal ethanol exposure on HPA responses to acute or intermittent stressors, our study investigated HPA responses to a chronic continuous stressor, cold stress (4 degrees C for 0, 1, or 3 days). We tested the hypothesis that prenatal ethanol exposure would result in increased plasma corticosterone (CORT) and adrenocorticotropin (ACTH) responses and increased peptide [corticotropin-releasing factor and vasopressin] mRNA levels in the paraventricular nucleus (PVN) of the hypothalamus compared to that in control animals. In addition, CORT and ACTH responses were measured after exposure to an acute stressor (i.p. isotonic saline injection), superimposed during chronic cold exposure, to examine possible sensitization of the HPA response to the acute stress. Thus, blood samples were collected at the end of each of the three periods of cold exposure, either before (0 min) or 15 min after acute stress. The subjects were adult male and female Sprague-Dawley rat offspring from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) treatment groups. Exposure to cold stress resulted in significant body weight loss in E males at 1 day and in both males and females of all prenatal treatment groups by 3 days of cold stress. Males in all prenatal groups also exhibited significant increases in adrenal weight:body weight ratios. Cold stress alone (0 min condition) increased CORT levels in E males and overall ACTH levels in E males and females compared to controls. ACTH levels were also higher overall in E compared to control males after acute stress (15 min condition). Sensitization of the CORT response to acute stress was observed in males but not females across all prenatal treatment groups. Corticotropin-releasing factor and vasopressin mRNA levels in the PVN were not significantly affected by prenatal treatment or chronic cold stress in either males or females. In contrast, both males and females displayed increases in PVN thyrotropin-releasing hormone (TRH) mRNA levels after cold stress. These data support and extend previous work demonstrating differential effects of prenatal ethanol exposure on HPA responsiveness of male and female offspring, and suggest that E males may be more vulnerable to the effects of chronic cold stress than E females.
Asunto(s)
Frío/efectos adversos , Sistema Hipotálamo-Hipofisario/fisiopatología , Sistema Hipófiso-Suprarrenal/fisiopatología , Efectos Tardíos de la Exposición Prenatal , Estrés Fisiológico/fisiopatología , Hormona Adrenocorticotrópica/sangre , Animales , Autorradiografía , Peso al Nacer/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Química Encefálica/efectos de los fármacos , Química Encefálica/fisiología , Enfermedad Crónica , Femenino , Hidrocortisona/sangre , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Inmunohistoquímica , Masculino , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Embarazo , Radioinmunoensayo , Ratas , Ratas Sprague-Dawley , Transcortina/metabolismoRESUMEN
Prenatal ethanol exposure and stress have each been shown to have significant effects on the immune system. This study examined the possible interactive effects of prenatal ethanol exposure and exposure to stress later in life on the immune system. Differential vulnerability to these challenges in female and male offspring was assessed. At 5 to 6 months of age, female and male offspring from prenatal ethanol-exposed (E), pair-red (PF), and ad libitum-fed control (C) conditions were exposed to 0, 1 or 3 days of cold (4 degrees C). At the end of the cold period, the proliferative response of splenic lymphocytes to the mitogens concanavalin A (Con A) and pokeweed mitogen (PWM) was assessed. The data demonstrate a significant interactive effect between prenatal ethanol exposure and cold stress in female offspring. After 1 day of cold stress, E females had significantly increased PWM-induced lymphocyte proliferation compared with PF and C females, and significantly increased Con A-induced lymphocyte proliferation compared with PF females. There were no differences in PWM or Con A-induced lymphocyte proliferation among E, PF, and C females after 0 or 3 days of cold stress, nor among E, PF, and C males on any test day. Regardless of prenatal treatment, females exposed to 1 or 3 days of cold had significantly greater basal plasma corticosterone levels than females not exposed to cold. In contrast, only E males exposed to 1 or 3 days of cold had significantly increased basal plasma corticosterone levels, compared with E males not exposed to cold; PF and C males showed no significant change in basal corticosterone after cold stress. These data demonstrate that, in response to the challenge of cold stress, changes in lymphocyte proliferation to PWM and Con A may occur selectively in E females. Moreover, the interactive effects of prenatal ethanol and cold stress may result in enhanced rather than suppressed immune responsiveness.
Asunto(s)
Aclimatación/inmunología , Regulación de la Temperatura Corporal/inmunología , Trastornos del Espectro Alcohólico Fetal/inmunología , Activación de Linfocitos/inmunología , Animales , Proteínas Portadoras/sangre , Frío/efectos adversos , Corticosterona/sangre , Femenino , Tolerancia Inmunológica/inmunología , Embarazo , Ratas , Ratas Sprague-DawleyRESUMEN
This study evaluated the effects of surrogate fostering as a procedure to control for postnatal effects of ethanol on the maternal female that may indirectly affect the offspring. Effects of fostering on the development of splenic lymphocytes, as well as possible differential effects of fostering on female and male offspring were examined. Litters from prenatal ethanol exposed (E), pair-fed (PF), and ad libitum-fed control (C) conditions were fostered at birth to surrogate untreated dams who had given birth within the same 12-hr period, or were reared by their biological mothers. At 15 and 60 days of age, offspring from each of the conditions were sacrificed and splenic leukocytes were enumerated and analyzed for expression of differentiation antigens, using flow cytometry. At 15 days of age, fostering reduced the percentages of CD45RA+ and CD5+ cells in E compared with PF and in PF compared with C offspring, and reduced the percentage of CD4+ cells in E compared with C offspring. Fostering also had differential effects on E and C offspring, resulting in reduced percentages of CD45RA+ and CD5+ cells in fostered E compared with nonfostered E offspring, but increased percentages of CD45RA+, CD5+, and CD8+ cells in fostered C compared with nonfostered C offspring. Fostering also down-regulated CD5 antigen expression in E compared with C offspring and up-regulated CD4 antigen expression in C offspring compared with their nonfostered counterparts. At 60 days of age, E females overall had higher percentages of CD45RA+ cells compared with C females and higher percentages of CD4+ cells compared with PF and C females. Nonfostered E females had higher percentages of CD5+ cells than nonfostered C females. In contrast, E males overall had greater percentages of CD4+ cells compared with PF and C males. Among males, the percentage of CD5+ cells was increased in nonfostered E compared with nonfostered C, whereas the percentages of CD45RA+ and CD5+ cells were decreased in fostered E males compared with nonfostered E. For both females and males in the nonfostered condition there were no effects of prenatal ethanol treatment on differentiation antigen expression. However, after fostering, E females had higher CD45RA and CD5 antigen expression compared with PF and C females, whereas E males had increased CD4 antigen expression and C males had decreased CD5 antigen expression compared with their nonfostered counterparts. These data demonstrate that fostering at birth has differential effects on splenic lymphocyte populations in E, PF, and C offspring. Moreover, the effect of fostering varies with age and has differential long-term effects on female and male offspring. Thus, rather than serving as a control for indirect maternal effects of ethanol on offspring, fostering appears to be a treatment in itself and may actually confound the effects of prenatal ethanol exposure by differentially affecting E, PF, and C females and males.
Asunto(s)
Trastornos del Espectro Alcohólico Fetal/inmunología , Medio Social , Subgrupos de Linfocitos T/inmunología , Animales , Antígenos CD/análisis , Femenino , Citometría de Flujo , Masculino , Embarazo , Ratas , Ratas Sprague-Dawley , Factores SexualesRESUMEN
The present study was undertaken to assess the possible interactive effects of prenatal ethanol exposure and stress in adulthood on lymphocyte populations in rat offspring, and to examine differential vulnerability of males and females to these challenges. Male and female offspring from prenatal ethanol-exposed (E), pair-fed, and ad libitum-fed control conditions were exposed to a 3-week chronic intermittent stress regimen in adulthood. Animals were exposed to two of six different stressors daily, one each at random times in the morning and afternoon, with the same pair of stressors being repeated every 4 days. Following the 3-week stress period, lymphocytes from four compartments (peripheral blood, spleen, thymus, and cervical lymph nodes) were analyzed for expression of differentiation antigens. Data demonstrate that, whereas a number of the effects of prenatal ethanol on lymphocyte populations appeared to be nutritionally mediated, the additional challenge of exposure to stressors differentially affected animals exposed to ethanol prenatally and appeared to have effects primarily in male offspring. Stressed E males had a greater reduction in the number of pan T-cells in the thymus and peripheral blood, compared with nonstressed E males, but showed an increased peripheral blood pan T-antigen expression. Stressed E males also had reduced numbers of peripheral blood CD4+ T cells compared to nonstressed E males [corrected].(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Etanol/toxicidad , Trastornos del Espectro Alcohólico Fetal/inmunología , Subgrupos Linfocitarios/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Estrés Psicológico/complicaciones , Animales , Relación CD4-CD8/efectos de los fármacos , Femenino , Tolerancia Inmunológica/efectos de los fármacos , Tolerancia Inmunológica/inmunología , Subgrupos Linfocitarios/inmunología , Masculino , Embarazo , Ratas , Ratas Sprague-Dawley , Valores de Referencia , Caracteres Sexuales , Estrés Psicológico/inmunología , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunologíaRESUMEN
Ethanol is a recognized immunosuppressive agent in the chronic alcoholic. However, the effects of ethanol exposure on the developing immune system have not been extensively investigated. This study evaluated the effects of early postnatal ethanol exposure, via breast milk, on splenic lymphocyte differentiation antigen expression in offspring reared by ethanol-fed mice. Maternal mice were fed a liquid diet containing 20% ethanol-derived calories during pregnancy (E-P), pregnancy and lactation (E-PL), or lactation (E-L). Ad libitum-fed (C) and pair-fed (PF) control groups, fed a control liquid diet, were included. Expression of differentiation antigens on splenic lymphocytes from 21-day-old offspring reared by females in 1 of the 3 ethanol exposure conditions was evaluated by flow cytometry. Offspring reared by E-P females had similar numbers of splenic lymphocytes as offspring reared by C and pair-fed during pregnancy (PF-P) females. In contrast, offspring reared by E-PL and E-L females had fewer splenic lymphocytes than both PF-PL and PF-L (respectively), and C offspring. The number of Thy 1.2+, CD4+, CD8+, and IgG+ (B-cell) splenic lymphocytes was reduced in E-PL and E-L offspring compared with PF and C offspring. E-P offspring had fewer CD4+ and IgG+ splenic lymphocytes than C, but not PF-P, offspring. The percentage of Thy 1.2+ splenic lymphocytes was significantly reduced among E-PL and E-L offspring compared with PF-PL and PF-L (respectively), and C offspring.(ABSTRACT TRUNCATED AT 250 WORDS)