Ovine placenta at high altitudes: Comparison of animals with different times of adaptation to hypoxic environment

Parraguez, Vı́ctor H.; Atlagich, Miljenko; Dı́az, Rodrigo; Cepeda, Raquel; González, Carlos; Reyes, M. De los; Bruzzone, M; Behn, Claus; Raggi, Luis A.

doi:10.1016/j.anireprosci.2005.11.003

Cited by 28 publications

(29 citation statements)

References 20 publications

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“…Arterial PO 2 in the triplets (21.2 Ϯ 1.2 mmHg) is much higher than in the growth-restricted lambs in heat-stressed pregnancies [11.7 Ϯ 1.2 mmHg (41)] and carunclectomized ewes [14.1 Ϯ 0.1 mmHg (15)]. Prolonged maternal hypobaric hypoxia can result in reduced birth weight in sheep (32), and this has also been reported in some but not all studies of high-altitude hypoxia (51,52). However, the results of the present study, showing no relationship between arterial PO 2 and birth weight, and a significant positive relationship between glucose concentration and birth weight (Fig.…”

Section: Monitored Blood Gas Andmentioning

confidence: 79%

Changes in fetal lamb arterial blood gas and acid-base status with advancing gestation

Rurak

Bessette

2013

American Journal of Physiology-Regulatory, Integrative and Comp

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To determine whether there are changes in blood gas and acid-base status with advancing gestation in the fetal lamb, similar to that reported in the human fetus, blood gas, acid-base, and blood metabolite values were measured in 447 control, arterial blood samples from 108 chronically instrumented fetal lambs between 103 and 146 days gestation. With advancing gestation, Po(2), pH, O(2) saturation, and O(2) content fell significantly, while Pco(2) and hemoglobin concentration increased. Blood glucose and lactate concentrations were unchanged, although the lactate level increased with decreasing Po(2), particularly when below ~13 mmHg. Multiple linear regression indicated that increasing fetal number was associated with decreased Po(2) and glucose level and increased pH, HCO(3)(-), base excess, and lactate concentration. Hemoglobin concentration was higher in female than male lambs. Overall, there was a linear relationship between glucose concentration and birth weight. It is concluded that in fetal lambs as in the human fetus, there are changes in blood gas and acid-base status with advancing gestation. This may be due to the decrease in fetal weight-normalized uterine and umbilical blood flows than occurs in these and other species as gestation proceeds. In addition, the reduced birth weight in twin and triplet lambs may be due to hypoglycemia rather than hypoxemia.

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Section: Monitored Blood Gas Andmentioning

confidence: 79%

Changes in fetal lamb arterial blood gas and acid-base status with advancing gestation

Rurak

Bessette

2013

American Journal of Physiology-Regulatory, Integrative and Comp

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“…; Mayhew, ; Parraguez et al . ). Although the specific morphological adaptations of the 13% H mouse placenta differed at the two stages of pregnancy, their net outcome was similar with respect to increasing the placental capacity for transport of nutrients and O 2 to the fetus (Fowden et al .…”

Section: Discussionmentioning

confidence: 97%

“…; Parraguez et al . ). Similar increases in placental vascularity and diffusion capacity have been observed in guinea pigs exposed to hypoxia for most of pregnancy (Bacon et al .…”

Section: Introductionmentioning

confidence: 97%

Placental phenotype and resource allocation to fetal growth are modified by the timing and degree of hypoxia during mouse pregnancy

Higgins

Vaughan

Liger

et al. 2015

The Journal of Physiology

113

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Key points Hypoxia is a major cause of fetal growth restriction, particularly at high altitude, although little is known about its effects on placental phenotype and resource allocation to fetal growth.In the present study, maternal hypoxia induced morphological and functional changes in the mouse placenta, which depended on the timing and severity of hypoxia, as well as the degree of maternal hypophagia.Hypoxia at 13% inspired oxygen induced beneficial changes in placental morphology, nutrient transport and metabolic signalling pathways associated with little or no change in fetal growth, irrespective of gestational age.Hypoxia at 10% inspired oxygen adversely affected placental phenotype and resulted in severe fetal growth restriction, which was due partly to maternal hypophagia.There is a threshold between 13% and 10% inspired oxygen, corresponding to altitudes of ∼3700 m and 5800 m, respectively, at which the mouse placenta no longer adapts to support fetal resource allocation. This has implications for high altitude human pregnancies. AbstractThe placenta adapts its transport capacity to nutritional cues developmentally, although relatively little is known about placental transport phenotype in response to hypoxia, a major cause of fetal growth restriction. The present study determined the effects of both moderate hypoxia (13% inspired O2) between days (D)11 and D16 or D14 and D19 of pregnancy and severe hypoxia (10% inspired O2) from D14 to D19 on placental morphology, transport capacity and fetal growth on D16 and D19 (term∼D20.5), relative to normoxic mice in 21% O2. Placental morphology adapted beneficially to 13% O2; fetal capillary volume increased at both ages, exchange area increased at D16 and exchange barrier thickness reduced at D19. Exposure to 13% O2 had no effect on placental nutrient transport on D16 but increased placental uptake and clearance of 3H‐methyl‐d‐glucose at D19. By contrast, 10% O2 impaired fetal vascularity, increased barrier thickness and reduced placental 14C‐methylaminoisobutyric acid clearance at D19. Consequently, fetal growth was only marginally affected in 13% O2 (unchanged at D16 and −5% at D19) but was severely restricted in 10% O2 (−21% at D19). The hypoxia‐induced changes in placental phenotype were accompanied by altered placental insulin‐like growth factor (IGF)‐2 expression and insulin/IGF signalling, as well as by maternal hypophagia depending on the timing and severity of the hypoxia. Overall, the present study shows that the mouse placenta can integrate signals of oxygen and nutrient availability, possibly through the insulin‐IGF pathway, to adapt its phenotype and optimize maternal resource allocation to fetal growth during late pregnancy. It also suggests that there is a threshold between 13% and 10% inspired O2 at which these adaptations no longer occur.

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“…) while others reported increased weight and decreased efficiency under the influence of chronic hypoxia (Parraguez et al . ; Richter et al . ; Herrera et al .…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular function in term fetal sheep conceived, gestated and studied in the hypobaric hypoxia of the Andean altiplano

Herrera

Rojas

Krause

et al. 2015

The Journal of Physiology

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Key pointsr High altitude developmental hypoxia causes intrauterine growth restriction and cardiovascular programming. However, some mammals exposed chronically to high-altitude hypoxia have less growth restriction suggesting certain protection.r Cardiovascular defence mechanisms during acute fetal hypoxia divert blood flow from the periphery towards the brain, heart and adrenals. In contrast, little is known about the cardiovascular defence mechanisms during chronic fetal hypoxia.r Here, we established the cardiovascular responses in fetal sheep that were conceived, gestated, born and studied at 3600 m. The data suggest that chronically hypoxic pregnant ewes and their fetuses have evolved different mechanisms from sea level pregnancies to withstand chronic hypoxia.r The cardiovascular responses to acute hypoxia are blunted in the chronically hypoxic fetus.These findings points towards compensatory mechanisms in the highland fetus at the level of the cells and molecules rather than mounting major cardiovascular responses, saving oxygen not easily available in the Alto Andino.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 ß90% 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 (ß10% O 2 ) 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 E. A. Herrera and R. T. Rojas contributed equally to this work. 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.

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Ovine placenta at high altitudes: Comparison of animals with different times of adaptation to hypoxic environment

Cited by 28 publications

References 20 publications

Changes in fetal lamb arterial blood gas and acid-base status with advancing gestation

Changes in fetal lamb arterial blood gas and acid-base status with advancing gestation

Placental phenotype and resource allocation to fetal growth are modified by the timing and degree of hypoxia during mouse pregnancy

Cardiovascular function in term fetal sheep conceived, gestated and studied in the hypobaric hypoxia of the Andean altiplano

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