Cardiovascular function in term fetal sheep conceived, gestated and studied in the hypobaric hypoxia of the Andean altiplano
Emilio A. HerreraRodrigo RojasBernardo J. KrauseGermán EbenspergerRoberto V. ReyesDino A. GiussaniJulian T. ParerAníbal J. Llanos
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Abstract:
High-altitude hypoxia causes intrauterine growth restriction and cardiovascular programming. However, adult humans and animals that have evolved at altitude show certain protection against the effects of chronic hypoxia. Whether the highland fetus shows similar protection against high altitude gestation is unclear. We tested the hypothesis that high-altitude fetal sheep have evolved cardiovascular compensatory mechanisms to withstand chronic hypoxia that are different from lowland sheep. We studied seven high-altitude (HA; 3600 m) and eight low-altitude (LA; 520 m) pregnant sheep at ∼90% gestation. Pregnant ewes and fetuses were instrumented for cardiovascular investigation. A three-period experimental protocol was performed in vivo: 30 min of basal, 1 h of acute superimposed hypoxia (∼10% O2) and 30 min of recovery. Further, we determined ex vivo fetal cerebral and femoral arterial function. HA pregnancy led to chronic fetal hypoxia, growth restriction and altered cardiovascular function. During acute superimposed hypoxia, LA fetuses redistributed blood flow favouring the brain, heart and adrenals, whereas HA fetuses showed a blunted cardiovascular response. Importantly, HA fetuses have a marked reduction in umbilical blood flow versus LA. Isolated cerebral arteries from HA fetuses showed a higher contractile capacity but a diminished response to catecholamines. In contrast, femoral arteries from HA fetuses showed decreased contractile capacity and increased adrenergic contractility. The blunting of the cardiovascular responses to hypoxia in fetuses raised in the Alto Andino may indicate a change in control strategy triggered by chronic hypoxia, switching towards compensatory mechanisms that are more cost-effective in terms of oxygen uptake.Keywords:
Hypoxia
Intrauterine growth restriction
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The plasma concentration of ovine chorionic somatomammotropin (oCS) was measured by homologous RIA in samples obtained from 56 chronically catheterized ovine fetuses, aged 66 days of gestation to term (147 days), and from their mothers. oCS concentrations from either ewe or fetus within 5 days of surgery were elevated compared to samples taken at least 6 days after surgery. In fetuses at least 6 days postoperative, a negative correlation (P < 0.001) was observed between fetal oCS concentration and gestational age. Between 81–100 days of gestation, the mean fetal oCS concentration was 80.0 ± 2.0 ng/ ml, and by 131–140 days of gestation, it had fallen to 37.7 ± 4.1 ng/ml. The mean maternal oCS concentration between 80–100 days of gestation was 54.5 ± 23.4 ng/ml and rose to a maximal concentration of 433.5 ± 93 ng/ml at 121–130 days. The ratio of fetal to maternal oCS concentration was 1.2 ± 0.4 in pregnancies less than 100 days of gestation and fell to 0.14 ± 0.04 at term. Both fetal and maternal oCS concentrations between 111–130 days of gestation were significantly higher in twin as compared to singleton pregnancies. These results demonstrate that the relative concentration of oCS in fetal and maternal circulations changes as gestation progresses. Fetal acidemia in late gestation was associated with marked increases in fetal oCS concentrations.
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Plasma ACTH and cortisol levels in the bovine fetuses over the period of 5 to 9 months of gestation and in the neonates immediately after birth and at 5 days old were studied. In the bovine fetuses, the plasma ACTH levels ranged from 60.8 +/- 17.8 to 71.3 +/- 19.7 pg/ml over the period of 5 to 7 months of gestation. It increased rapidly to 239.2 +/- 261.5 pg/ml at 8 months and to 406.9 +/- 409.4 pg/ml at 9 months of gestation. In the neonates immediately after birth it decreased to 182.3 +/- 110.7 pg/ml. The plasma cortisol levels ranged from 3.23 +/- 2.12 to 3.85 +/- 2.52 ng/ml over the period of 5 to 8 months of gestation and increased to 8.10 +/- 4.88 ng/ml at 9 months of gestation. It then increased rapidly to 88.35 +/- 42.78 ng/ml in the neonates immediately after birth. The correlation between plasma ACTH and cortisol levels in the fetuses of 5 to 7 months of gestation was not significant, but in the fetuses of 8 and 9 months of gestation and neonates were significant. However, especially immediately after birth, the increase in plasma cortisol occurred without a concomitant rise in plasma ACTH. According to these findings, it is suggested that the pituitary-adrenocortical axis in bovine fetus matures in the later stage of gestation and an increase of sensitivity in the fetal adrenal gland to ACTH may serve as a trigger for the onset of parturition.
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Ovine PRL (oPRL) was determined by homologous RIA on plasma samples drawn from ovine fetuses with chronically implanted vascular catheters from 71 days gestation to term (147 days). Plasma PRL was first detected (>1.0 ng/ml) at 87 days and remained low before 110 days gestation [2.1 ± 0.3 ng/ml (mean ± SE)]. Fetal PRL concentration rose to 14.7 ± 2.5 ng/ml at 111–120 days gestation, to 26.0 ± 2.6 ng/ml at 121–130 days, and to 37.5 ± 2.6 ng/ml at 131–140 days. At term (141–150 days), the mean PRL concentration was 37.8 ± 2.0 ng/ml. Significantly lower PRL concentrations were found in the late gestation fetus during fetal surgery when compared with levels in the chronically catheterized fetus. In samples drawn from the chronically catheterized neonatal lamb, PRL concentrations were lower (15.6 ± 3.7 ng/ml) in the first neonatal week than in the term fetus. However, by the fourth neonatal week, PRL concentrations had risen to levels similar to the late gestation fetus (28.0 ±4.1 ng/ml). No correlation between maternal PRL concentrations and gestational age was observed between 58–148 days gestation. The MCR of oPRL in the ovine fetus was estimated from PRL concentrations achieved by the constant infusion of oPRL into five fetuses between 114–135 days: The calculated clearance (9.27 ± 1.26 ml/min) was similar when corrected for body mass to that previously reported in the infant lamb The pattern of circulating PRL in the ovine fetus is similar to that in the human fetus. In both species, PRL concentrations are low until the third trimester, then rise to high levels, in close temporal relationship to the previously reported increase in fetal estrogen concentrations which have been postulated to have a major influence on the secretion of PRL by the fetal pituitary gland.
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The pregnant female rats were treated i. p. with a single dose of adenine at 300 or 350 mg/kg once during major organogenesis of the embryo. Near-term fetuses were examined for external, internal and skeletal malformations and the followings were resulted.(1) Fetal resorption was increased when 300 mg/kg of the compound was treated on day 9 or 14 of gestation.(2) Body weight of live fetuses was lowered in all the groups treated at 300 mg/kg.(3) The fetuses with digital malformations were found with significantly high frequency in group treated at 300 mg/kg on day 14 of gestation.(4) Significantly high frequency of the fetuses with internal malformations was resulted by treatment at 300 mg/kg on day 8,9,10,12 or 13 of gestation.(5) Significantly high frequency of skeletal malformations was shown in all the treated groups except group treated on day 15 of gestation.(6) With such indices as fetal resorption, body weight, external, internal and skeletal malformations, a dose effect relation was clearly shown in groups treated on day 10 or 14 of gestation.(7) Less embryopathic effects of adenine was shown in the rats compared to the mice treated with its lower dosage.
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Pregnant SPF Wistar rats and ICR/Swiss albino mice were injected in the tail vein with 85SrCl2 with 0.05 mM inactive carrier (SrCl2) given in volumes of 0.1 ml. The activity in the injected volume was about 14 MBq per kg of rat and 13 MBq per kg of mouse. The animals were injected at 2 or 13 days of gestation. The activity retained by the fetuses was quantitatively determined at three stages of the fetal intrauterine development: in rats at 14, 16 and 21 days of gestation, in mice at 14, 16 and 20 days of gestation. The activity of fetuses and/or placentas with fetal membranes was measured using a TESLA automatic gamma counter. Results indicate that fetuses of mice retained a significantly (P less than 0.01) greater percent of strontium activity than fetuses of rats. The highest specific activities (the percentage of total activity retained per gram of fetal tissue) were found in the late pregnancy period (at 21 days of gestation in rats and 20 days of gestation in mice) in animals that were injected with the radionuclide at 13 days of gestation.
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ABSTRACT. Thirty primigravidae took part in a prospective study of attitudes to the fetus, carried out by means of a series of semi-structured, tape-recorded interviews. The degree of development of the fetus was grossly underestimated in the first trimester. By mid-pregnancy their ideas about the fetus had become more accurate and all gave realistic descriptions by 36 weeks gestation. Although most women had difficulty in believing that the fetus really existed in early pregnancy, a minority already had an established relationship with the fetus by 8–12 weeks of gestation. Maternal fetal "attachment''was present in 63% of women by 18–22% weeks and 92% by 36 weeks gestation.
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