Nicol M B, Hirst J J, Walker D, Thorburn G D
Department of Physiology, Monash University, Clayton, Victoria, Australia.
J Endocrinol. 1997 Mar;152(3):379-86. doi: 10.1677/joe.0.1520379.
Placental progesterone synthesis exposes the fetus to high levels of progesterone and progesterone metabolites during late gestation which may influence fetal behaviour. To determine the role of maternal progesterone synthesis in the control of fetal arousal state and fetal breathing movements (FBM), the effect of raising and lowering maternal progesterone concentrations was examined in chronically catheterised fetal sheep. Fetal and maternal vascular catheters, fetal tracheal and amniotic fluid catheters as well as electrodes for recording fetal electrocortical (ECoG), electro-ocular (EOG) and nuchal muscle electromyographic (EMG) activity were implanted between 118 and 122 days gestational age (GA). Progesterone, 100 mg, administered twice daily i.m. for 3 days (130-133 days GA) resulted in a marked elevation in maternal plasma progesterone concentrations (370 +/- 121%, n = 5, P < 0.05), but had no effect on fetal plasma concentrations. Fetal EOG episodes and the duration of fetal behavioural arousal were significantly suppressed throughout the progesterone treatment period (74.4-81.1% and 58-65% respectively, P < 0.05, n = 5). Four ewes received Trilostane (25 mg i.v.), a 3 beta-hydroxysteroid dehydrogenase inhibitor, between 136 and 140 days GA. Maternal and fetal progesterone concentrations were significantly lowered by 60 min after treatment (19.8 +/- 8.0% and 39.5 +/- 24.3% respectively, P < 0.05). The incidence of fetal EOG activity increased from a pretreatment level of 26.8 +/- 1.5 min/h to 30.3 +/- 2.8 min/h at 1-6 h and to 35.0 +/- 1.7 min/h (P < 0.05) during the 7-12 h after Trilostane treatment. The duration of FBM episodes was significantly higher at 1-6 h and 7-12 h after Trilostane treatment (19.5 +/- 3.0 and 23.6 +/- 5.5 min/h respectively, P < 0.05) compared with pretreatment levels (11.2 +/- 1.2 min/h). We conclude that increasing maternal progesterone levels suppresses fetal EOG activity and behavioural arousal, whereas reducing maternal progesterone synthesis leads to an elevation of EOG activity and FBM.
胎盘孕酮合成使胎儿在妊娠晚期暴露于高水平的孕酮及其代谢产物中，这可能会影响胎儿的行为。为了确定母体孕酮合成在控制胎儿觉醒状态和胎儿呼吸运动（FBM）中的作用，研究人员在长期插管的胎羊中检测了提高和降低母体孕酮浓度的效果。在妊娠118至122天（GA）之间，植入胎儿和母体血管导管、胎儿气管和羊水导管以及用于记录胎儿脑电图（ECoG）、眼电图（EOG）和颈部肌肉肌电图（EMG）活动的电极。在妊娠130至133天（GA）期间，每天两次肌肉注射100mg孕酮，持续3天，导致母体血浆孕酮浓度显著升高（370±121%，n = 5，P < 0.05），但对胎儿血浆浓度没有影响。在整个孕酮治疗期间，胎儿EOG发作次数和胎儿行为觉醒持续时间均显著受到抑制（分别为74.4 - 81.1%和58 - 65%，P < 0.05，n = 5）。4只母羊在妊娠136至140天（GA）期间静脉注射曲洛司坦（25mg），一种3β - 羟类固醇脱氢酶抑制剂。治疗后60分钟，母体和胎儿孕酮浓度显著降低（分别为19.8±8.0%和39.5±24.3%，P < 0.05）。胎儿EOG活动发生率从治疗前的26.8±1.5分钟/小时在曲洛司坦治疗后1 - 6小时增加到30.3±2.8分钟/小时，并在7 - 12小时增加到35.0±1.7分钟/小时（P < 0.05）。与治疗前水平（11.2±1.2分钟/小时）相比，曲洛司坦治疗后1 - 6小时和7 - 12小时FBM发作持续时间显著增加（分别为19.5±3.0和23.6±5.5分钟/小时，P < 0.05）。我们得出结论，提高母体孕酮水平会抑制胎儿EOG活动和行为觉醒，而降低母体孕酮合成会导致EOG活动和FBM增加。
