Nutrient restriction in early ovine pregnancy stimulates C-type natriuretic peptide production

2017 ◽  
Vol 29 (3) ◽  
pp. 575 ◽  
Author(s):  
Sengodi Madhavan ◽  
Timothy C. R. Prickett ◽  
Eric A. Espiner ◽  
Graham K. Barrell

C-type natriuretic peptide (CNP), a paracrine growth factor promoting vasodilation and angiogenesis, is upregulated in human and ovine pregnancy in response to vascular stress or nutrient restriction (NR) in late gestation. Postulating that maternal plasma CNP products are increased by modest NR (50% of metabolisable energy requirement) early in pregnancy, and further enhanced by litter size, we studied serial changes of maternal plasma CNP in pregnant ewes receiving a normal (NC, n = 12) or restricted (NR, n = 13) diet from Day 30 to Day 93 or 94 of gestation. Liveweight of NR ewes was 10 kg less than that of NC ewes at slaughter. Plasma CNP products increased progressively after Day 40 and were higher in NR (P < 0.05) ewes after Day 60; they were also enhanced by litter size (P < 0.01) and were positively associated with increased placental efficiency. In contrast, whereas fetal and placental weight were reduced by NR, fetal plasma CNP products (Day 93/94) were not affected. We conclude that increases in CNP during rapid placental growth are further enhanced by both increasing nutrient demands and by reduced supply, presumably as part of an adaptive response benefitting placental–fetal exchange.

2012 ◽  
Vol 24 (8) ◽  
pp. 1063 ◽  
Author(s):  
B. A. McNeill ◽  
G. K. Barrell ◽  
M. J. Ridgway ◽  
M. P. Wellby ◽  
T. C. R. Prickett ◽  
...  

The factors regulating the greatly elevated concentrations of maternal plasma C-type natriuretic peptide (CNP) forms in ruminant pregnancy are largely unknown, but nutrient status is likely to be important. Previous work has shown that increases in maternal plasma CNP, sourced from the placenta, occur in response to caloric restriction in late gestation. Whether oversupply of nutrients also regulates CNP secretion in pregnancy has not been studied. Hypothesising that CNP in fetal and maternal tissues will be responsive to both deficiency and excess, we studied changes in CNP and a cosecreted fragment, namely N-terminal pro-CNP (NTproCNP), during short-term periods of caloric restriction (CR) and loading (CL). Twin-bearing ewes received CR (fasted Days 121–124), CL (Days 110–124) or control maintenance diets. During CR, fetal plasma CNP forms, insulin-like growth factor (IGF)-1 and liveweight all fell, and maternal plasma NTproCNP increased. During CL, fetal IGF-1 increased, whereas CNP forms and liveweight were unchanged, as were maternal concentrations of CNP forms. The high abundance of CNP peptides in placental tissues was unaffected by these short-term changes in nutrient supply. We conclude that CNP in the fetal–maternal unit is acutely responsive to undernutrition, but is unaffected by oversupply in 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


1991 ◽  
Vol 260 (2) ◽  
pp. R389-R395 ◽  
Author(s):  
M. Keller-Wood ◽  
C. E. Wood

In the sheep, maternal plasma cortisol is increased in late pregnancy, and fetal plasma cortisol and adrenocorticotropic hormone (ACTH) rise precipitously in late gestation. In many species, the placenta contains ACTH. These experiments were designed to test whether the ovine placenta contains ACTH and whether there is net secretion of ACTH by the uteroplacental unit into either the maternal or fetal circulation. Pregnant ewes and their fetuses were prepared with maternal and fetal arterial and uterine and umbilical venous catheters. Arterial and venous samples were taken from both sides of the placenta before and during hypoxia induced by the ewe breathing 9-11% O2, and arteriovenous (a-v) differences in ACTH, PO2, PCO2, and progesterone were analyzed. A positive a-v difference in PO2 (48.2 +/- 3.4 mmHg) and negative a-v differences in PCO2 and progesterone (-3.5 +/- 0.7 mmHg and -25 +/- 5 ng/ml, respectively) were found across the placenta in the ewe, and a positive a-v difference in PCO2 (4.8 +/- 0.9 mmHg) and negative a-v differences in PO2 and progesterone (-8.1 +/- 1.5 mmHg and -13 +/- 3 ng/ml, respectively) were found across the placenta in the fetus, indicating that the umbilical and uterine venous catheters were properly placed. Hypoxia decreased fetal and maternal arterial PO2 from 22.8 +/- 1.3 to 13.8 +/- 0.7 and from 98.8 +/- 3.3 to 37.0 +/- 2.6 mmHg, respectively, and increased fetal and maternal arterial ACTH immunoreactivity from 95 +/- 60 to 2,676 +/- 795 and from 149 +/- 21 to 275 +/- 88 pg/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


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.


1994 ◽  
Vol 142 (3) ◽  
pp. 417-425 ◽  
Author(s):  
M Silver ◽  
A L Fowden

Abstract The present study was carried out on 19 chronically catheterized mares and fetuses in late gestation (term >320 days). In six animals which were monitored up to the time of delivery of a live foal, plasma and amniotic fluid cortisol concentrations remained low until 4–5 days before parturition when there was a rapid, significant rise (P<0·05) which was not accompanied by any corresponding changes in maternal plasma cortisol. Circulating fetal ACTH concentrations became more variable close to delivery and ANOVA revealed no significant increases during this critical period, although a negative correlation between plasma ACTH and time to delivery was observed (P<0·05). Tests on fetal adrenal responsiveness to exogenous ACTH1–24 were carried out on ten animals. Before 295 days of gestation no significant increases in fetal plasma cortisol above its basal level of 20–30 nmol/l could be elicited by ACTH, administered as a single i.v. injection (1–2 μg/kg). By 304 ± 3 days (mean ± s.e.m.) small but significant (P<0·05) increments in plasma cortisol were detected after ACTH, while in the oldest group (313 ±2 days) significant (P<0·01) 50–60% increments were seen throughout the test period (2 h). Only one fetus was tested within 3 days of delivery and here a fourfold rise in plasma cortisol was evoked by ACTH. When changes in endogenous levels of circulating ACTH and cortisol were monitored every 15 min over 1·5- to 2-h periods in late gestation, rises in ACTH were only accompanied by concomitant increases in plasma cortisol in fetuses within 5 days of delivery (correlation coefficient r=0·58, P<0·01). Before this time, plasma cortisol concentrations remained at basal levels irrespective of any fluctuations in plasma ACTH. These findings indicate that the adrenal cortex of the fetal foal is relatively quiescent and insensitive to ACTH for most of the latter part of gestation, but that a short rapid escalation in circulating cortisol precedes its delivery. Journal of Endocrinology (1994) 142, 417–425


Endocrinology ◽  
2009 ◽  
Vol 150 (10) ◽  
pp. 4777-4783 ◽  
Author(s):  
Bryony A. McNeill ◽  
Graham K. Barrell ◽  
Martin Wellby ◽  
Timothy C. R. Prickett ◽  
Timothy G. Yandle ◽  
...  

Abstract Circulating concentrations of C-type natriuretic peptide (CNP) and a related amino terminal fragment (NTproCNP) were measured at weekly intervals from preconception to 3 wk postpartum in ewes with twins (n = 8) and nonpregnant ewes (n = 8). In contrast to low and stable values in nonpregnant ewes (CNP, 0.75 ± 0.08; NTproCNP, 22 ± 2 pmol/liter), CNP forms increased abruptly at 40–50 d of gestation and rose to peak values (CNP, 31 ± 5, NTproCNP, 270 ± 16 pmol/liter) at about d 120. Approximately 7 d prepartum, the concentration of both CNP forms fell precipitously to preconception values immediately postpartum. In separate studies, circulating maternal CNP forms were positively related to fetal number at d 120. Consistent with a major contribution from the placenta to circulating levels, the concentrations of CNP forms were elevated in the placentome (cotyledon: CNP, 18 ± 4, NTproCNP, 52 ± 10 pmol/g; caruncle: CNP, 13 ± 3, NTproCNP, 31 ± 6 pmol/g) and much higher than those of intercaruncular uterine tissue (CNP, 0.19 ± 0.05, NTproCNP, 0.98 ± 0.2 pmol/g) in late-gestation ewes (P &lt; 0.001, n = 4). These distinctive patterns of maternal plasma CNP forms, positive relation with fetal number, and greatly elevated protein concentrations in the placentome demonstrate the hormone’s strong relation to placental and fetal maturation. The findings provide a firm basis for future studies of the functional role of CNP in fetal-maternal welfare.


1992 ◽  
Vol 263 (4) ◽  
pp. F671-F679 ◽  
Author(s):  
M. E. Wlodek ◽  
R. Harding ◽  
G. D. Thorburn

Our aim was to determine the effects of prolonged removal of fetal urine during late gestation on fetal-maternal fluid and electrolyte relationships. We measured the volume and composition of fetal urine and amniotic and allantoic fluids and the composition of fetal and maternal plasma in sheep before and during continuous urine drainage, which began at 130 days of gestation and continued until the onset of labor; a control group was also studied. The response to fetal urine drainage occurred in two phases. In the "acute" phase (1-3 days), amniotic and allantoic fluid volumes decreased significantly, presumably due to their reabsorption into the fetal chorionic circulation or swallowing of amniotic fluid by the fetus. During the "chronic" phase, starting 3-5 days after urine drainage, a significant reversal in the transplacental osmotic gradient occurred due to a decrease in maternal plasma osmolality. During the entire drainage period (14.1 +/- 1.1 days, mean +/- SE, n = 5) at least 542 ml/day of water and 24 mmol/day of electrolytes passed from the mother into the fetal circulation and fetal plasma osmolality was unchanged. We conclude that, despite the loss of substantial water and electrolytes, the fetus is able to maintain its growth and fluid and electrolyte homeostasis by obtaining water and electrolytes initially from the amniotic and allantoic fluids and subsequently from its mother. The movement of water and electrolytes to the fetus would have been facilitated by the reversed transplacental osmotic gradient.


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


1989 ◽  
Vol 67 (1) ◽  
pp. 1-4 ◽  
Author(s):  
S. Mulay ◽  
D. R. Varma

Transplacental passage of 125I-labelled synthetic rat atrial natriuretic peptide (ANP) was investigated in 20-day pregnant rats under pentobarbitone anesthesia. Although significant quantities of radioactivity were detected in the fetal plasma after maternal injections and in the maternal plasma after fetal injections of 125I-labelled synthetic ANP, no fraction of the placentally transferred radioactivity was due to intact ANP. Despite a rapid maternal and fetal metabolism of ANP, both maternal and fetal plasma radioactivity remained relatively stable for at least 3 h and less than 10% of the injected radioactivity was excreted in the maternal urine during a 90-min period. It is concluded that ANP is not transported in either direction across the placenta in rats.Key words: atrial natriuretic peptide, placental barrier, urinary excretion, maternal metabolism, fetal metabolism.


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