Wilson M E, Handa R J
Program in Molecular Biology, Loyola University, Stritch School of Medicine, Maywood, IL 60153, USA.
Alcohol. 1997 Sep-Oct;14(5):497-501. doi: 10.1016/s0741-8329(97)00037-2.
Previous studies have shown that fetal alcohol exposure (FAE) alters reproductive function in both male and female rats. In females, FAE delays the onset of puberty, reduces a preovulatory-like LH surge, and results in an early onset of acyclicity. In males exposed to ethanol in utero, the perinatal surge of testosterone is reduced. During the infantile period of the female rat, there is a dramatic increase in plasma follicle-stimulating hormone (FSH), which is thought to play a role in initiating ovarian activity and perhaps the onset of puberty. In this study, we determined the effects of FAE on the patterns of gonadotropin secretion during the infantile period [postnatal days (PND) 8-21] in both male and female rats. Timed pregnant dams were fed a liquid diet containing 35% ethanol-derived calories during the final week of gestation. Control dams were fed either an isocaloric diet with sucrose substituted for ethanol (pair fed, PF) or laboratory chow (chow fed, CF). Male and female pups were sacrificed on PND 8, 10, 12, 15, 18, and 21, and trunk blood was collected. In males, LH levels decreased to a nadir on PND 18, and this decrease was blunted by FAE (p < 0.05). In contrast, FSH secretion was not altered by FAE. In females, plasma FSH levels were greater than males, and increased to peak on PND 12. This FSH peak was significantly delayed in FAE females (p < 0.02). There was no age-related change in LH levels in FAE females, and LH levels were not altered by FAE. The delayed peak of FSH secretion by FAE correlates with the delay in puberty previously seen in females. To investigate this further, we examined the possibility that the delay in the peak of serum FSH in FAE females is due to a reduced number of FSH-producing gonadotrophs. FSH-containing gonadotrophs were identified by immunocytochemistry. Cell counts of FSH-immunoreactive cells in pituitaries from PND 8, 15, and 21 control-fed and FAE female rats showed developmental increases in the number of FSH gonadotrophs per unit area (p < 0.001), but no treatment differences were observed. Overall, these data show that fetal alcohol exposure can alter gonadotropin secretion in infantile life in male and female rats. Importantly, the delay in FSH secretion in females may ultimately play a role in the delay in puberty observed in the FAE female rat.
先前的研究表明,胎儿酒精暴露(FAE)会改变雄性和雌性大鼠的生殖功能。在雌性大鼠中,FAE会延迟青春期的开始,减少类似排卵前的促黄体生成素(LH)激增,并导致早期无排卵周期的出现。在子宫内暴露于乙醇的雄性大鼠中,围产期睾酮激增会减少。在雌性幼鼠期,血浆促卵泡生成素(FSH)会急剧增加,这被认为在启动卵巢活动以及可能在青春期开始中起作用。在本研究中,我们确定了FAE对雄性和雌性大鼠幼年期[出生后天数(PND)8 - 21]促性腺激素分泌模式的影响。在妊娠最后一周,对定时怀孕的母鼠喂食含35%乙醇热量的液体饮食。对照母鼠喂食用蔗糖替代乙醇的等热量饮食(配对喂食,PF)或实验室饲料(正常喂食,CF)。在PND 8、10、12、15、18和21处死雄性和雌性幼崽,并收集躯干血。在雄性大鼠中,LH水平在PND 18降至最低点,而这种下降被FAE减弱(p < 0.05)。相比之下,FAE未改变FSH分泌。在雌性大鼠中,血浆FSH水平高于雄性,并在PND 12升至峰值。FAE雌性大鼠中这个FSH峰值显著延迟(p < 0.02)。FAE雌性大鼠中LH水平没有与年龄相关的变化,并且FAE也未改变LH水平。FAE导致的FSH分泌峰值延迟与先前在雌性大鼠中观察到的青春期延迟相关。为了进一步研究这一点,我们研究了FAE雌性大鼠血清FSH峰值延迟是否是由于产生FSH的促性腺细胞数量减少的可能性。通过免疫细胞化学鉴定含FSH的促性腺细胞。对PND 8、15和21的对照喂食和FAE雌性大鼠垂体中FSH免疫反应性细胞进行细胞计数,结果显示单位面积内FSH促性腺细胞数量呈发育性增加(p < 0.001),但未观察到处理差异。总体而言,这些数据表明胎儿酒精暴露可改变雄性和雌性大鼠幼年期的促性腺激素分泌。重要的是,雌性大鼠中FSH分泌的延迟可能最终在FAE雌性大鼠中观察到的青春期延迟中起作用。