Effect of long-term infusion of ovine corticotrophin-releasing factor in the immature ovine fetus

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

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


1985 ◽  
Vol 63 (5) ◽  
pp. 500-508 ◽  
Author(s):  
G. Jenkin ◽  
G. Jorgensen ◽  
G. D. Thorburn ◽  
J. E. Buster ◽  
P. W. Nathaniels

Premature induction of delivery in fetuses infused with graded doses of cortisol was brought about in 123.5 ± 7.7 h (mean ± SEM, n = 6) after the start of cortisol infusion. This treatment caused a rise in fetal plasma cortisol similar to that observed at normal delivery. Maternal and fetal progesterone and 20α-dihydroprogesterone concentrations decreased to basal levels during infusion of cortisol to the fetus. Induction of premature delivery was delayed or prevented by concomitant treatment of the ewe with progestagen. Maternal intramuscular injection of 100 mg progesterone, 2 times daily, prevented delivery in four of four ewes treated during the time that cortisol was infused into the fetus (11–13 days). Maternal plasma progesterone and 20α-dihydroprogesterone concentrations were maintained during this period, but fetal plasma progesterone concentrations decreased to the same extent as in the fetuses infused with cortisol alone. A single intramuscular injection of 250 mg of medroxyprogesterone acetate to ewes on the day before commencement of infusion of cortisol to the fetus prevented delivery in four of six ewes during the time that cortisol was infused for 9, 13, 14, and 15 days, respectively. One ewe delivered a live lamb at 133.5 h and another at 147.7 h after the start of infusion of cortisol to the fetus. Maternal and fetal plasma cortisol, progesterone, and 20α-dihydroprogesterone concentrations were similar to those observed during infusion of cortisol alone to the fetus. Although fetal cortisol concentrations rose in a similar fashion, and to a similar extent, in all three groups during infusion of cortisol to the fetus, fetal 11-desoxycortisol concentrations only rose above basal levels close to the time of delivery in cortisol-infused fetuses or, in the progestagen-treated groups, when the fetus showed signs of being stressed.


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.


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


1990 ◽  
Vol 124 (1) ◽  
pp. 99-107 ◽  
Author(s):  
R. J. MacIsaac ◽  
R. S. Carson ◽  
A. P. Horvath ◽  
E. M. Wintour

ABSTRACT This study was designed to investigate the effects of pulsatile infusion of ACTH into ovine fetuses on the endocrine changes that precede parturition, the timing of birth and the subsequent survival of the lamb. Where appropriate, these parameters were compared with fetuses infused with pulses of saline and uninfused normal term fetuses. Ten fetuses received a 15-min infusion of synthetic ACTH(1–24) (79 ng/min) from day 125 (n=9) or day 126 (n=1) of gestation. Seven fetuses were born prematurely within 174±14 h (mean ± s.e.m.) after the commencement of the infusion, i.e. at 132 ± 0·6 days, whilst three died in utero at 130–131 days. When born all lambs could breath, walk and suckle. Of the seven premature lambs, four died 2–10 days after parturition but three survived for at least 12 months after birth. Fetuses infused with pulses of ACTH exhibited intermittent but very large increases in plasma ACTH values, with the first pulse, on day 1, increasing ACTH values from 5·1 ± 1·1 to 140 ± 31·3 pmol/l (P<0·001). At the next sampling time, ACTH values were not significantly different from preinfusion values. A similar plasma ACTH profile was observed on each subsequent day of ACTH treatment. In contrast, fetuses (n=4) infused with pulses of saline between 125 and 131 days exhibited fetal plasma concentrations of ACTH which ranged between 2 and 12 pmol/l for the majority of the time. Of the uninfused fetuses (n=8) that were studied during the last week of normal gestation, seven were born alive at 148·9± 1·0 days of gestation, whilst one lamb was stillborn at 146 days. In these fetuses, plasma concentrations of ACTH increased slowly to 35·6 ±2·4 pmol/l on the day before delivery with a further increase to 76·4± 3·9 pmol/l occurring on the day of delivery. In fetuses infused with pulses of ACTH there was also a significant (P< 0·001) increase in the fetal cortisol to corticosterone ratio from a value of 2·9 before the commencement of the infusion to 69·1 just before birth. In ewes bearing uninfused fetuses born at normal term, maternal plasma concentrations of progesterone on day 4 before delivery were significantly (P<0·05) lower than on day 5 before delivery. In comparison, in ewes bearing fetuses infused with pulses of ACTH, a significant (P<0·05) decrease from maternal plasma concentrations of progesterone on day 5 before delivery did not occur until day 1 before delivery. In ewes bearing uninfused or prematurely delivered fetuses infused with pulses of ACTH, maternal plasma concentrations of oestrogen did not significantly (P<0·01) increase until the day of parturition. It is concluded that a minimum of 6–7 days of ACTH treatment is required by the fetal adrenal for the induction of cortisol synthesis sufficient to produce the birth of viable lambs. However, premature lambs have a 57% mortality rate in the 2- to 10-day period after birth. Journal of Endocrinology (1990) 124, 99–107


1987 ◽  
Vol 113 (1) ◽  
pp. 97-101 ◽  
Author(s):  
M. J. Taylor

ABSTRACT An inhibitor of 3β-hydroxysteroid dehydrogenase (3β-HSD) activity was administered to sheep in late pregnancy. A rapid fall in plasma progesterone concentrations followed, associated with premature delivery by all animals 44±3 h (s.e.m.) after administration of inhibitor. A significant (about twofold) increase in plasma concentrations of oestradiol-17β was detected immediately before delivery. These results demonstrate, in contrast to previous reports, that 3β-HSD inhibitors have the capacity consistently to induce premature delivery associated with increased oestrogen release in sheep. J. Endocr. (1987) 113, 97–101


1988 ◽  
Vol 116 (3) ◽  
pp. 381-385 ◽  
Author(s):  
T. M. Nguyen ◽  
A. Halhali ◽  
H. Guillozo ◽  
M. Garabedian ◽  
S. Balsan

ABSTRACT The effect of thyroparathyroidectomy (TPTX) on the plasma concentrations of the vitamin D metabolites (25-(OH)D, 24,25-(OH)2D and 1,25-(OH)2D) has been studied in pregnant rats and their fetuses during the last quarter of gestation. Maternal and fetal vitamin D metabolites were not significantly affected by TPTX. A significant increase in plasma 1,25-(OH)2D concentrations was observed in both TPTX and control mothers and fetuses from days 19 to 21. Fetal and maternal plasma 25-(OH)D were positively correlated in both control and TPTX groups. Such a correlation was also found for 24,25-(OH)2D in the two groups. In contrast, a positive correlation between maternal and fetal plasma concentrations of 1,25-(OH)2D was found in TPTX but not in control rats. These data suggest that major alterations in calcium metabolism, such as that produced by maternal TPTX, are insufficient to affect the changes in maternal and fetal plasma 1,25-(OH)2D during late pregnancy significantly. They also suggest that parathyroid hormone, thyroxine, and/or calcitonin may control a possible placental transfer of 1,25-(OH)2D in the rat. J. Endocr. (1988) 116, 381–385


1980 ◽  
Vol 239 (3) ◽  
pp. E208-E214 ◽  
Author(s):  
R. L. Prior

The metabolism of glucose and lactate by the ovine fetus (123-128 days of gestation) was studied; a primed, continuous infusion of [2-3H]glucose and [U-14C]lactate into the brachial vein of six fetuses was used. Fetal plasma lactate concentrations averaged 2.12 +/- 0.25 mM and glucose concentrations averaged 9.3 +/- 1.3 mg/100 ml. Total plasma turnover of lactate was 5.22 +/- 0.7 nmol/h and that of glucose was 3.48 +/- 0.63 nmol x h-1 x kg fetal weight-1. Lactate was converted to glucose at a rate of 1.35 +/- 0.64 mmol x h-1 x kg fetal weight-1, which represented 21.6 +/- 6.0% of the lactate turnover. The percentage of glucose coming from lactate was 48.9 +/- 15.2. The specific activity of maternal plasma glucose was less than 4% of the specific activity of glucose observed in fetal plasma. No radioactivity could be detected in maternal plasma lactate. The data show that the ovine fetus or the fetal-placental unit can convert lactate to glucose by days 123-128 of gestation. A general model presented describes carbohydrate metabolism in the ovine placenta and fetus.


1986 ◽  
Vol 66 (4) ◽  
pp. 995-1001
Author(s):  
G. J. MEARS

Plasma concentrations of growth hormone (GH) and insulin were monitored in 11 chronically cannulated ovine fetuses and their mothers during the last month of gestation to obtain information on the role that these hormones have in determining fetal growth rate. Maternal plasma GH and insulin concentrations were independent of stage of gestation and lamb birth weights. Fetal plasma insulin concentrations were episodic in nature, independent of stage of gestation, and tended to be higher in fetuses that were heavier at birth. Fetal plasma GH concentrations were only slightly episodic in nature, were tenfold higher than maternal levels at 116–124 d gestation and increased by approximately another 25% prior to parturition. Fetal plasma GH concentrations were negtively correlated with lamb birth weights. In twin preparations, fetal plasma GH concentrations were significantly lower in the twin that was heaviest at birth. The lower GH concentrations found in faster growing fetuses are suggestive of a more rapid metabolic clearance of GH by the tissues of these animals. The results indicate that circulating fetal GH and, possibly, insulin are involved in determining the rate of ovine-fetal growth. Key words: Ovine birth weights, fetal GH, fetal insulin, fetal growth


2013 ◽  
Vol 25 (2) ◽  
pp. 439 ◽  
Author(s):  
Cheryl J. Ashworth ◽  
Margaret O. Nwagwu ◽  
Harry J. McArdle

This study compared maternal plasma amino acid concentrations, placental protein secretion in vitro and fetal body composition and plasma amino acid and hormone concentrations in feto–placental units from the smallest and a normally-sized fetus carried by Large White × Landrace or Meishan gilts on Day 100 of pregnancy. Compared with Large White × Landrace, Meishan placental tissue secreted more protein and Meishan fetuses contained relatively more fat and protein, but less moisture. Fetal plasma concentrations of insulin, triiodothryonine, thyroxine and insulin-like growth factor (IGF)-II were higher in Meishan than Large White × Landrace fetuses. In both breeds, fetal cortisol concentrations were inversely related to fetal size, whereas concentrations of IGF-I were higher in average-sized fetuses. Concentrations of 10 amino acids were higher in Large White × Landrace than Meishan gilts, while glutamine concentrations were higher in Meishan gilts. Concentrations of alanine, aspartic acid, glutamic acid and threonine were higher in Meishan than Large White × Landrace fetuses. Average-sized fetuses had higher concentrations of asparagine, leucine, lysine, phenylalanine, threonine, tyrosine and valine than the smallest fetus. This study revealed novel genotype and fetal size differences in porcine maternal–fetal amino acid status and fetal hormone and metabolite concentrations.


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