title: Effect of alteration of maternal plasma progesterone concentrations on fetal behavioural state during late gestation.
abstract: 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.
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria, Australia.
authors.forename: M B
authors.initials: MB
authors.lastname: Nicol
authors.forename: J J
authors.initials: JJ
authors.lastname: Hirst
authors.forename: D
authors.initials: D
authors.lastname: Walker
authors.forename: G D
authors.initials: GD
authors.lastname: Thorburn
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D000818:Animals; D001143:Arousal / Q000187:drug effects; D013196:Dihydrotestosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D004576:Electromyography; D004585:Electrooculography; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005333:Fetus / Q000502:physiology*; D005865:Gestational Age; D009068:Movement / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood*; D011374:Progesterone / Q000097:blood* / Q000494:pharmacology; D012132:Respiratory Muscles / Q000187:drug effects; D012756:Sheep / Q000097:blood*
chemical_list: D013196:Dihydrotestosterone; D011374:Progesterone; D015096:3-Hydroxysteroid Dehydrogenases; C009954:trilostane