Effect of hypobaric hypoxia on lamb intrauterine growth: comparison between high- and low-altitude native ewes

Parraguez, Vı́ctor H.; Atlagich, Miljenko; Dı́az, Rodrigo; Bruzzone, M; Behn, Claus; Raggi, Luis A.

doi:10.1071/rd04060

Cited by 33 publications

(28 citation statements)

References 46 publications

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“…In our study, both groups of lambs received the same nutrition, so the changes observed in pulmonary arterial pressure and growth restriction appear to be independent of nutrition. Accordingly, the effects on fetal growth restriction and mortality of developmental hypoxia at high altitude have been shown to be independent of the maternal nutritional status and of highland hypobaria in other species, since fetal growth restriction persists in ewes undergoing pregnancy at high altitude with food intake values similar to those as sea level pregnancies (23, 39). These effects have also been shown in the chick embryo, where incubation at high altitude of sea level eggs with oxygen supplementation completely prevented the high altitude-induced fetal growth restriction and mortality (17).…”

Section: Discussionmentioning

confidence: 99%

“…The diminished production of CO by the pulmonary circulation determined in this study may play a putative role in the maintenance of persistent pulmonary hypertension of the newborn at sea level. In addition, chronic developmental hypoxia is known to result in lung hypoplasia and immaturity, pulmonary edema, and altered endothelial function (2, 20, 39, 46). Alterations in the synthesis and function of vasoconstrictors such as ET-1, as reported in this paper, thromboxane, IGF, serotonin, and leukotriene C 4 /D 4 have also been implicated in the pulmonary hypertensive phenotype during chronic hypoxia (29, 45).…”

Section: Discussionmentioning

confidence: 99%

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Long-term exposure to high-altitude chronic hypoxia during gestation induces neonatal pulmonary hypertension at sea level

Herrera

Riquelme

Ebensperger³

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

107

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We determined whether postnatal pulmonary hypertension induced by 70% of pregnancy at high altitude (HA) persists once the offspring return to sea level and investigated pulmonary vascular mechanisms operating under these circumstances. Pregnant ewes were divided into two groups: conception, pregnancy, and delivery at low altitude (580 m, LLL) and conception at low altitude, pregnancy at HA (3,600 m) from 30% of gestation until delivery, and return to lowland (LHL). Pulmonary arterial pressure (PAP) was measured in vivo. Vascular reactivity and morphometry were assessed in small pulmonary arteries (SPA). Protein expression of vascular mediators was determined. LHL lambs had higher basal PAP and a greater increment in PAP after NG-nitro-l-arginine methyl ester (20.9 ± 1.1 vs. 13.7 ± 0.5 mmHg; 39.9 ± 5.0 vs. 18.3 ± 1.3 mmHg, respectively). SPA from LHL had a greater maximal contraction to K+ (1.34 ± 0.05 vs. 1.16 ± 0.05 N/m), higher sensitivity to endothelin-1 and nitroprusside, and persistence of dilatation following blockade of soluble guanylate cyclase. The heart ratio of the right ventricle-to-left ventricle plus septum was higher in the LHL relative to LLL. The muscle area of SPA (29.3 ± 2.9 vs. 21.1 ± 1.7%) and the protein expression of endothelial nitric oxide synthase (1.7 ± 0.1 vs. 1.1 ± 0.2), phosphodiesterase (1.4 ± 0.1 vs. 0.7 ± 0.1), and Ca2+-activated K+ channel (0.76 ± 0.16 vs. 0.30 ± 0.01) were greater in LHL compared with LLL lambs. In contrast, LHL had decreased heme oxygenase-1 expression (0.82 ± 0.26 vs. 2.22 ± 0.44) and carbon monoxide production (all P < 0.05). Postnatal pulmonary hypertension induced by 70% of pregnancy at HA promotes cardiopulmonary remodeling that persists at sea level.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Long-term exposure to high-altitude chronic hypoxia during gestation induces neonatal pulmonary hypertension at sea level

Herrera

Riquelme

Ebensperger³

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

107

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“…; Penninga & Longo, ; Parraguez et al . ). Taken together, these observations suggest that there are adaptations in materno‐fetal resource allocation during chronic hypoxia that help to maintain fetal growth, although the mechanisms operating in vivo remain unknown.…”

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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“…) and in domestic animal species (mainly sheep) introduced to high plateaus (Lanino ; De Carolis ; Parraguez et al. , ). The low reproductive efficiency is even more marked in newcomers to high altitude, by acute exposition to hypoxia, both humans (Moore et al.…”

Section: Introductionmentioning

confidence: 99%

“…) and sheep (Parraguez et al. , ). These facts are of main importance, firstly, for human medicine; approximately 140 millions of people inhabit at altitudes above 2500 m above sea level (m.a.s.l.…”

Section: Introductionmentioning

confidence: 99%

Fertility of a High‐Altitude Sheep Model is Compromised by Deficiencies in Both Preovulatory Follicle Development and Plasma LH Availability

Parraguez

Diaz

Cofré

et al. 2014

Reprod Domestic Animals

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At high altitude, hypoxia and/or oxidative stress may compromise fertility. This study tested the relative effect of short- or long-term exposure to high-altitude hypobaric hypoxia and oxidative stress in sheep on preovulatory follicle dynamics and gonadotrophin secretion. Thus, growth dynamics, stereidogenic function and competence to ovulate of preovulatory follicles, as well as FSH and LH availability throughout the entire oestrous cycle, were compared among sheep native from low and high altitude, and sheep newcomers to high altitude. The results indicates that short-term exposure in sheep newcomers to high altitude has a deleterious effect on both the ovarian function (affecting preovulatory follicular development) and the pituitary function (diminishing plasma LH availability). On the other hand, there were no detected differences in the preovulatory follicular development in sheep adapted to high altitude for generations and, conversely, LH secretion was increased, which suggests an adaptive mechanism. The treatment with antioxidant agents during a relative short period for the time of folliculogenesis (approximately 1 month and a half) changed substantially the development of preovulatory follicles in short-term exposed sheep to similar patterns than in sheep native and living to both high and low altitude. These results highlight the role of oxidative stress in the detriment of the reproductive function in individuals recently exposed to high-altitude hypoxic environment.

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Effect of hypobaric hypoxia on lamb intrauterine growth: comparison between high- and low-altitude native ewes

Cited by 33 publications

References 46 publications

Long-term exposure to high-altitude chronic hypoxia during gestation induces neonatal pulmonary hypertension at sea level

Long-term exposure to high-altitude chronic hypoxia during gestation induces neonatal pulmonary hypertension at sea level

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

Fertility of a High‐Altitude Sheep Model is Compromised by Deficiencies in Both Preovulatory Follicle Development and Plasma LH Availability

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