Effect of alteration of maternal plasma progesterone concentrations on fetal behavioural state during late gestation

1997 ◽  
Vol 152 (3) ◽  
pp. 379-386 ◽  
Author(s):  
M B Nicol ◽  
J J Hirst ◽  
D Walker ◽  
G D Thorburn

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 3β-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. Journal of Endocrinology (1997) 152, 379–386

1997 ◽  
Vol 9 (8) ◽  
pp. 767 ◽  
Author(s):  
Kelly J. Crossley ◽  
Marcus B. Nicol ◽  
Jonathan J. Hirst ◽  
David W. Walker ◽  
Geoffrey D. Thorburn†

The high rate of progesterone synthesis by the placenta in late gestation exposes the ovine fetus to high concentrations of progesterone and its metabolites that may affect activity of the fetal brain. The aim of this study was to determine the effect of inhibiting maternal progesterone synthesis on sleep–wake activity in fetal sheep. Fetal and maternal vascular catheters, a fetal tracheal catheter, and electrodes for recording fetal electrocortical (ECoG), electro-ocular (EOG) and nuchal muscle electromyographic (EMG) activity were implanted. At 128–131 days gestation, progesterone production was inhibited by an injection of trilostane (50 mg), a 3β-hydroxysteroid dehydrogenase inhibitor. Vehicle solution or progesterone (3 mg h -1 ) was then infused into the ewe between 6 and 12 h after the trilostane treatment. Maternal progesterone concentrations were significantly reduced from 1–24 h after trilostane treatment (P < 0·05) when followed by vehicle infusion. Fetal breathing movements (FBM), EOG, nuchal muscle EMG, and behavioural arousal increased 12 h after trilostane treatment (P < 0 · 05). In contrast, there was no change in fetal arousal, EOG, EMG or FBM activities when progesterone was infused after the trilostane treatment. These findings show that progesterone can influence fetal behaviour, and indicates that normal progesterone production tonically suppresses arousal, or wakefulness in the fetus.


1989 ◽  
Vol 120 (3) ◽  
pp. 459-464 ◽  
Author(s):  
I. C. McMillen ◽  
R. Nowak

ABSTRACT We have investigated the effect of pinealectomy of ewes in pregnancy on the presence of the diurnal rhythm in fetal and maternal plasma concentrations of melatonin. Six ewes were pinealectomized between 104 and 118 days of gestation. Fetal and maternal blood samples were collected during 24-h periods between 125 and 140 days of gestation in the pinealectomized ewes and in an intact control (n = 4). There was a significant diurnal rhythm in both fetal and maternal plasma concentrations of melatonin in the control group. In this group, the fetal and maternal plasma melatonin concentrations were significantly higher in the dark (128·4±6·2 and 192·2± 10·7 pmol/l respectively) than in the light (46·2 ± 4·2 and 25·8 ± 2·1 pmol/l respectively). However there was no diurnal rhythm in either the fetal or maternal plasma melatonin concentrations in the pinealectomized group between 125 and 140 days of gestation. In contrast to the control animals, there was also no light–dark difference in the fetal or maternal plasma melatonin concentrations in four pinealectomized animals sampled frequently in the 3–7 days preceding delivery (mean length of gestation 146·5 days). However, in the pinealectomized sheep there was a gradual increase in the combined light–dark fetal plasma melatonin concentrations during late gestation from 27·9 ± 2·8 pmol/l (at 15–20 days before delivery) to 95·2± 14·1 pmol/l on the day of delivery. We have therefore demonstrated that the maternal pineal is the major source of the diurnal rhythm in maternal and fetal plasma melatonin concentrations. However maternal pinealectomy does not appear to remove all the melatonin immunoreactivity from the maternal and fetal plasma in late gestation. Journal of Endocrinology (1989) 120, 459–464


2015 ◽  
Vol 308 (4) ◽  
pp. E306-E314 ◽  
Author(s):  
Satya S. Houin ◽  
Paul J. Rozance ◽  
Laura D. Brown ◽  
William W. Hay ◽  
Randall B. Wilkening ◽  
...  

Reduced fetal glucose supply, induced experimentally or as a result of placental insufficiency, produces an early activation of fetal glucose production. The mechanisms and substrates used to fuel this increased glucose production rate remain unknown. We hypothesized that in response to hypoglycemia, induced experimentally with maternal insulin infusion, the fetal liver would increase uptake of lactate and amino acids (AA), which would combine with hormonal signals to support hepatic glucose production. To test this hypothesis, metabolic studies were done in six late gestation fetal sheep to measure hepatic glucose and substrate flux before (basal) and after [days (d)1 and 4] the start of hypoglycemia. Maternal and fetal glucose concentrations decreased by 50% on d1 and d4 ( P < 0.05). The liver transitioned from net glucose uptake (basal, 5.1 ± 1.5 μmol/min) to output by d4 (2.8 ± 1.4 μmol/min; P < 0.05 vs. basal). The [U-13C]glucose tracer molar percent excess ratio across the liver decreased over the same period (basal: 0.98 ± 0.01, vs. d4: 0.89 ± 0.01, P < 0.05). Total hepatic AA uptake, but not lactate or pyruvate uptake, increased by threefold on d1 ( P < 0.05) and remained elevated throughout the study. This AA uptake was driven largely by decreased glutamate output and increased glycine uptake. Fetal plasma concentrations of insulin were 50% lower, while cortisol and glucagon concentrations increased 56 and 86% during hypoglycemia ( P < 0.05 for basal vs. d4). Thus increased hepatic AA uptake, rather than pyruvate or lactate uptake, and decreased fetal plasma insulin and increased cortisol and glucagon concentrations occur simultaneously with increased fetal hepatic glucose output in response to fetal hypoglycemia.


1986 ◽  
Vol 111 (3) ◽  
pp. 469-475 ◽  
Author(s):  
E. M. Wintour ◽  
R. J. Bell ◽  
R. S. Carson ◽  
R. J. MacIsaac ◽  
G. W. Tregear ◽  
...  

ABSTRACT Synthetic ovine corticotrophin-releasing factor (oCRF) was infused continuously into the jugular veins of six ovine fetuses for 5–11 days. Two fetuses receiving 0·1 and 1·0 μg oCRF/h from gestational days 134 and 135 respectively, lambed prematurely on days 141 and 140 respectively. Three out of four fetuses receiving oCRF at 2·4 μg/h, from 125 days of gestation, delivered spontaneously at 131, 131 and 136 days, whilst one died in utero at 132 days. Two fetuses receiving vehicle only or oCRF intra-amniotically, were born at 148 and 145 days respectively, whilst six fetuses chronically cannulated but not infused were born at 149·8 ±2·1 (s.d.) days. In ewes lambing at term, maternal plasma progesterone concentrations were 41·4±11·4 (s.e.m.; n = 5), 28·8±7·8 (n = 6), 17·1 ±4·8 (n = 5) and 7·9± 1·1 (n = 4) nmol/l on 3, 2, 1 and 0 days respectively before the lambs were born. No such decrease in maternal plasma progesterone concentrations was seen in the oCRF-infused fetuses. Fetal plasma concentrations of immunoreactive ACTH were maintained above normal in oCRF-infused fetuses, but some desensitization to bolus oCRF injections occurred in these fetuses. Four of the five fetuses born prematurely were sufficiently mature to survive, being able to stand, breathe and suckle. It is concluded that continuous oCRF infusions into immature fetuses can accelerate maturation of a number of organs and systems culminating in the premature delivery of viable lambs. J. Endocr. (1986) 111, 469–475


1989 ◽  
Vol 256 (5) ◽  
pp. R1103-R1110 ◽  
Author(s):  
C. E. Wood

Hypotension in fetal sheep stimulates reflex decreases in heart rate and increases in the secretion of several hormones, including adrenocorticotropin (ACTH), cortisol, vasopressin, and renin. However, little is known about the afferent limb(s) of the reflex(es) controlling these responses. Fetal sheep between 122 and 134 days gestation were prepared with chronic vascular catheters, intravascular balloon-tipped catheters, and amniotic fluid catheters. Seven fetal sheep were also subjected to sinoaortic denervation, and nine remained intact. After recovery from surgery for 2-5 days, fetuses were subjected to a 10-min period of hypotension produced by vena caval obstruction, produced by inflation of balloons in the superior and inferior venae cavae. Vena caval obstruction produced decreases in fetal heart rate and increases in fetal plasma ACTH, vasopressin, and renin activity, which were related to the degree of hypotension. Prior sinoaortic denervation attenuated all of these responses. It is concluded that afferent fibers in the carotid sinus and/or aortic depressor nerves mediate part of the heart rate, ACTH, vasopressin, and renin responses to vena caval obstruction in late-gestation fetal sheep.


1988 ◽  
Vol 255 (3) ◽  
pp. R412-R417 ◽  
Author(s):  
C. E. Wood

Previous studies from this laboratory have demonstrated that intravenous infusions of hydrocortisone (cortisol) into fetal sheep at rates that produce plasma concentrations achieved during fetal stress inhibit fetal adrenocorticotropic hormone (ACTH) and renin secretion. The present study was designed to test for inhibition of fetal renin and ACTH after maternal adrenal secretion of cortisol. ACTH-(1-24) or saline infusion into 12 pregnant ewes (120-132 days gestation) at rates of 0, 1, 5, or 20 ng ACTH.kg-1.min-1 for 5 h produced dose-related increases in maternal plasma ACTH and cortisol concentrations and fetal plasma cortisol concentration. In the 20-ng.kg-1.min-1 group, increases in fetal plasma cortisol of 8.0 ng/ml (to 24.3 +/- 3.7 ng/ml) did not suppress basal fetal plasma renin activity. One hour after the end of the maternal vehicle or ACTH infusion, fetal ACTH secretion was stimulated by fetal intravenous infusion of sodium nitroprusside. In the 0-, 1-, and 5-ng.kg-1.min-1 groups, fetal ACTH responses to nitroprusside were suppressed in animals infused with ACTH. Together, these results indicate that the maternal adrenal secretion of cortisol inhibits stimulated secretion of ACTH but not renin in 120- to 132-day-gestation fetal sheep.


1991 ◽  
Vol 261 (4) ◽  
pp. R995-R1002 ◽  
Author(s):  
M. Keller-Wood ◽  
C. E. Wood

In the sheep, maternal plasma adrenocorticotropic hormone and cortisol are increased in late pregnancy, and fetal plasma cortisol and adrenocorticotropic hormone rise precipitously in late gestation. To test whether the ovine placenta secretes corticotropin-releasing factor (CRF) into either the maternal or fetal circulation, pregnant ewes and their fetuses were prepared with femoral arterial catheters and uterine and umbilical venous catheters. Samples were taken from all sites before and during hypoxia. There was no difference in CRF concentration across the placenta in the mothers or the fetuses under resting or hypoxemic conditions, but maternal and fetal arterial plasma CRF concentrations increased between 128 and 145 days. In a second study, maternal and fetal femoral venous plasma CRF concentrations were measured 1-19 days before spontaneous parturition. The mean concentration increased 8.6 +/- 0.6 pg/ml 11-19 days before parturition to 13.0 +/- 1.0 and 13.2 +/- 1.4 pg/ml in fetuses 4-8 and 1-3 days before parturition, respectively. Maternal plasma concentrations did not significantly increase in the days closer to parturition. These studies demonstrate that there are low but measurable CRF concentrations in fetal and maternal sheep plasma but that these are not the result of tonic placental secretion of CRF.


2005 ◽  
Vol 288 (1) ◽  
pp. R39-R45 ◽  
Author(s):  
L. J. Edwards ◽  
J. R. McFarlane ◽  
K. G. Kauter ◽  
I. C. McMillen

It has been proposed that maternal nutrient restriction may alter the functional development of the adipocyte and the synthesis and secretion of the adipocyte-derived hormone, leptin, before birth. We have investigated the effects of restricted periconceptional undernutrition and/or restricted gestational nutrition on fetal plasma leptin concentrations and fetal adiposity in late gestation. There was no effect of either restricted periconceptional or gestational nutrition on maternal or fetal plasma leptin concentrations in singleton or twin pregnancies during late gestation. In ewes carrying twins, but not singletons, maternal plasma leptin concentrations in late gestation were directly related to the change in ewe weight that occurred during the 60 days before mating [maternal leptin = 0.9 (change in ewe weight) + 7.8; r = 0.6, P < 0.05]. In twin, but not singleton, pregnancies, there was also a significant relationship between maternal and fetal leptin concentrations (maternal leptin = 0.5 fetal leptin + 4.2, r = 0.63, P < 0.005). The relative mass of perirenal fat was also significantly increased in twin fetal sheep in the control-restricted group (6.0 ± 0.5) compared with the other nutritional groups (control-control: 4.1 ± 0.4; restricted-restricted: 4.4 ± 0.4; restricted-control: 4.3 ± 0.3). In conclusion, the impact of maternal undernutrition on maternal plasma leptin concentrations during late gestation is dependent on fetal number. Furthermore, we have found that there is an increased fetal adiposity in the twins of ewes that experienced restricted nutrition throughout gestation, and this may be important in the programming of postnatal adiposity.


1986 ◽  
Vol 108 (3) ◽  
pp. 361-367 ◽  
Author(s):  
R. Habert ◽  
R. Picon

ABSTRACT The present study was performed to examine whether circulating progesterone regulates testicular testosterone production in the fetal rat. Progesterone levels in fetal plasma were found to increase from day 14·5 to day 16·5; thereafter they reached a plateau between days 16·5 and 18·5 (80 nmol/l) and decreased threefold between days 18·5 and 21·5. The addition of progesterone, within the range of normal plasma concentrations, induced a dose-dependent increase in testosterone produced in vitro by the testes on days 16·5 and 18·5 but not on day 20·5. However, in 18·5-day-old fetuses, individual plasma progesterone levels were not correlated with testicular testosterone production in vivo and in vitro. Furthermore, maternal bilateral ovariectomy induced a significant fall in plasma progesterone in 18·5-day-old fetuses; this was not associated with a reduction in plasma testosterone nor in testicular testosterone content, although the amount of testosterone secreted by the testis incubated in vitro was slightly but significantly reduced. It is concluded that circulating progesterone does not regulate testicular testosterone production in vivo although the testis may use plasma progesterone as a substrate. On day 18·5 after maternal ovariectomy, the decrease in plasma progesterone levels was similar in fetuses and mothers, suggesting that most fetal progesterone originates from maternal plasma. J. Endocr. (1986) 108, 361–367


1987 ◽  
Vol 114 (1) ◽  
pp. 65-72 ◽  
Author(s):  
I. C. McMillen ◽  
G. D. Thorburn ◽  
D. W. Walker

ABSTRACT We have measured fetal and maternal plasma concentrations of cortisol, prolactin, GH and glucose in samples collected during a 24-h period in 14 animals between 127 and 142 days of gestation. There was a significant increase in both the mean daily plasma cortisol concentration and mean daily coefficient of variation (C.V.) of plasma cortisol concentrations after 135 days of gestation. There was also a significant variation in the fetal plasma cortisol concentrations with a peak occurring at 19.00 h. There was a significant sinusoidal diurnal rhythm in the plasma prolactin concentrations in both the fetal sheep and pregnant ewe and the maximal prolactin concentrations occurred between 19.00 and 23.00 h (fetal) and 21.00 and 01.00 h (maternal). Although no significant diurnal variation was detected in fetal plasma GH concentrations, there was a significant sinusoidal diurnal rhythm in the plasma GH concentrations of the pregnant ewe and the maximal maternal GH concentrations occurred between 21.00 and 01.00 h. Both the fetal and maternal plasma glucose concentrations showed a significant sinusoidal diurnal rhythm. The maximal maternal and fetal glucose concentrations were measured between 21.00 and 01.00 h and between 23.00 and 03.00 h respectively. We have therefore established that diurnal variations in plasma cortisol and prolactin concentrations exist prenatally. Whether the presence of such hormonal rhythms reflects the activity of an endogenous fetal circadian pacemaker remains to be established. J. Endocr. (1987) 114, 65–72


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