Gilbert S G, Rice D C
Toxicology Research Division, Health and Welfare Canada, Ottawa, Ontario.
Fundam Appl Toxicol. 1991 Feb;16(2):299-308. doi: 10.1016/0272-0590(91)90114-j.
Pregnancy requires a variety of physiological adaptations to create an environment for the optimal development of the fetus. The widespread consumption of the methylxanthines especially caffeine and to a lesser extent theophylline by pregnant women suggests that it is important to determine whether these methylxanthines may influence maternal physiology during pregnancy. Forty female monkeys (Macaca fascicularis), randomly divided into three groups, were exposed to caffeine in their drinking water (0, 0.15, or 0.35 mg/ml) before, during, and after pregnancy. This exposure resulted in a dose-related increase in reproductive failure in the form of stillbirths, miscarriages, and decreased maternal weight gain. Blood and 24-hr urine samples were collected every 2 weeks for clinical chemistry analysis. There were a number of both pregnancy-related changes and treatment-related effects on the clinical chemistry measures. As expected, serum cholesterol and triglyceride levels declined during pregnancy for all dose groups but there were no treatment-related effects. Serum and urine creatinine levels were increased in both treated groups. Serum glucose levels, which usually decline during pregnancy, remained elevated in the high-dose group. Serum estrogen levels in the high-dose groups were depressed compared to those of the other two groups. These changes indicate that elevated serum levels of caffeine and its metabolites, particularly theophylline, may influence maternal physiology during pregnancy in the monkey.
怀孕需要多种生理适应性变化来为胎儿的最佳发育创造一个环境。孕妇广泛摄入甲基黄嘌呤,尤其是咖啡因,其次是茶碱,这表明确定这些甲基黄嘌呤是否会在孕期影响母体生理状况很重要。四十只雌性猕猴(食蟹猴)被随机分为三组,在怀孕前、怀孕中和怀孕后饮用含有咖啡因的水(浓度分别为0、0.15或0.35毫克/毫升)。这种接触导致以死产、流产和母体体重增加减少形式出现的生殖失败与剂量相关。每两周采集一次血液和24小时尿液样本进行临床化学分析。临床化学指标出现了许多与怀孕相关的变化以及与治疗相关的影响。正如预期的那样,所有剂量组在孕期血清胆固醇和甘油三酯水平均下降,但没有与治疗相关的影响。两个治疗组的血清和尿液肌酐水平均升高。通常在孕期会下降的血清葡萄糖水平在高剂量组中仍保持升高。与其他两组相比,高剂量组的血清雌激素水平降低。这些变化表明,血清中咖啡因及其代谢物,尤其是茶碱水平升高,可能会在孕期影响猕猴的母体生理状况。