Vitamin D status and metabolism in an ovine pregnancy model: effect of long-term, high-altitude hypoxia (original) (raw)
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Reproduction, fertility, and development, 2011
The present study evaluated the hypothesis that the effects of hypoxia on sheep pregnancies at high altitude (HA) are mediated by oxidative stress and that antioxidant vitamins may prevent these effects. Both HA native and newcomer ewes were maintained at an altitude of 3,589 m during mating and pregnancy. Control low altitude (LA) native ewes were maintained at sea level. Half of each group received daily oral supplements of vitamins C (500 mg) and E (350 IU) during mating and gestation. Near term, maternal plasma vitamin levels and oxidative stress biomarkers were measured. At delivery, lambs were weighed and measured, and placentas were recovered for macroscopic and microscopic evaluation. Vitamin concentrations in supplemented ewes were two- or threefold greater than in non-supplemented ewes. Plasma carbonyls and malondialdehyde in non-supplemented ewes were consistent with a state of oxidative stress, which was prevented by vitamin supplementation. Vitamin supplementation incre...
Plasma vitamin D metabolite levels in pregnant and nonpregnant ewes
Comparative Biochemistry and Physiology Part A: Physiology, 1990
Maternal calcium homeostasis during pregnancy is strained due to fetal mineral requirements for bone formation. 2. In most species, the mother adjusts to the mineral requirements of the fetus with alterations in her metabolism of vitamin D that include a decrease in nlasma 25-(0H)D levels and an increase in circulating , levels of the hormone, 1,25-(OH),D. 3. Plasma 25-(0H)D and 1,25-(OH),D levels in adult male, adult female and pregnant sheep were measured by specific radioreceptor binding assays. 4. Pregnancy did not alter circulating levels of 25(0H)D or I,2S-(OH)ZD in the sheep. 5. The pregnant ewe differs from al1 species studied to date in that maternal plasma 1,25-(OH), D levels do not rise as a resuh of pregnancy.
Reproduction, Fertility and Development, 2013
Sheep pregnancy in high-altitude environments frequently involves hypoxia and oxidative stress and causes intrauterine growth retardation. The adverse effects of altitude on fetal growth can be prevented by the administration of antioxidant vitamins, but the mechanisms responsible are not well known. The maintenance of a viable pregnancy depends largely on adequate placental steroidogenesis, especially in the last two-thirds of pregnancy. Thus, in the present study we evaluated the effect of antioxidant vitamins (C and E) on plasma concentrations of progesterone and 17β-oestradiol during the last two-thirds of high-altitude pregnancies in ewes both native and naïve to the high-altitude environment. In addition, pregnancy outcomes were evaluated by determining the bodyweight of newborn lambs. Sex steroid patterns differed between ewes with and without vitamin supplementation. Concentrations of plasma progesterone and 17β-oestradiol were significantly higher in the supplemented groups...
Nutrients, 2015
Vitamin D has garnered a great deal of attention in recent years due to a global prevalence of vitamin D deficiency associated with an increased risk of a variety of human diseases. Specifically, hypovitaminosis D in pregnant women is highly common and has important implications for the mother and lifelong health of the child, since it has been linked to maternal and child infections, small-for-gestational age, preterm delivery, preeclampsia, gestational diabetes, as well as imprinting on the infant for life chronic diseases. Therefore, factors that regulate vitamin D metabolism are of main importance, especially during pregnancy. The hormonal form and most active metabolite of vitamin D is calcitriol. This hormone mediates its biological effects through a specific nuclear receptor, which is found in many tissues including the placenta. Calcitriol synthesis and degradation depend on the expression and activity of CYP27B1 and CYP24A1 cytochromes, respectively, for which regulation is tissue specific. Among the factors that modify these cytochromes expression and/or activity are calcitriol itself, parathyroid hormone, fibroblast growth factor 23, cytokines, calcium and phosphate. This review provides a current overview on the regulation of vitamin D metabolism, focusing on vitamin D deficiency during gestation and its impact on pregnancy outcomes.
Pregnancy does not alter the metabolic clearance of 1,25-dihydroxyvitamin D in rats
The American journal of physiology, 1990
Increased circulating levels of 1,25-dihydroxyvitamin D [1,25(OH)2D] during pregnancy could be due to an increase in production or decrease in the metabolic clearance rate of 1,25(OH)2D. To answer this question an isotope dilution method was used to determine the clearance rate of 1,25(OH)2D in pregnant and aged-matched nonpregnant female rats. A bolus of 0.146 muCi 1,25(OH)2[3H]D3 was given to 60 pregnant and 60 aged-matched nonpregnant rats and the disappearance of the isotope was followed in these animals over the next 48 h. In 12 pregnant rats vs. 14 nonpregnant controls not injected with tracer, plasma calcium (9.6 +/- 0.41 vs. 10.7 +/- 0.17 mg/ml) and 25(OH)D (17.1 +/- 1.15 vs. 25.4 +/- 1.58 ng/ml) levels were significantly lower (P less than 0.01 and P less than 0.001), whereas plasma 1,25(OH)2D levels (110 +/- 16.1 pg/ml vs. 77 +/- 6.0 pg/ml) were significantly higher (P less than 0.05). Clearance rates of 1,25(OH)2D of 25.8 +/- 1.31 microliters/min in pregnant rats and 20.2...
Ascorbate prevents placental oxidative stress and enhances birth weight in hypoxic pregnancy in rats
The Journal of Physiology, 2012
• High-altitude pregnancy is associated with reduced oxygenation and placental complications, which can affect maternal and fetal outcome. However, most high-altitude populations are also impoverished and because maternal undernutrition itself is known to promote placental problems, the extent to which complications during high-altitude pregnancy could be due to maternal oxygen and/or nutrient restriction remains unclear. • The aim of the study was to investigate whether reduced placental oxygenation, independent of maternal undernutrition, increases maternal and placental oxidative stress and whether maternal treatment with vitamin C is protective. • The study shows that hypoxic pregnancy increased maternal circulating and placental molecular indices of oxidative stress. • Maternal vitamin C treatment was protective and increased birth weight. • The study offers insight to mechanism and intervention against the effects of high altitude on pregnancy.
PLOS ONE, 2015
Pregnancies at high-altitudes are influenced by hypoxia and oxidative stress and frequently affected by IUGR. However, a common thought is that early pregnant women visiting altitude have no major complications for gestation development, since IUGR is developed during the second half of pregnancy. Thus, using a well-characterized sheep-model, we aimed to determine whether long-and/or short-term exposure to high-altitude may affect maternal steroidogenesis and therefore embryo-fetal growth from conception. The second aim was to differentiate the relative role of hypoxia and oxidative stress by assessing the effects of supplementation with antioxidant agents during this early-pregnancy stage, which were previously found to be useful to prevent IUGR. The results indicate that both long-and shortterm exposure to high-altitude causes disturbances in maternal ovarian steroidogenesis and negatively affects embryo-fetal growth already during the very early stages of gestation, with the consequences being even worsened in newcomers to high-altitude. The supply of antioxidant during this period only showed discrete effects for preventing IUGR. In conclusion, the present study gives a warning for clinicians about the risks for early-pregnant women when visiting high-altitude regions and suggests the need for further studies on the effects of the length of exposure and on the interaction of the exposure with the pregnancy stage.
Adrenocortical and adipose responses to high-altitude-induced, long-term hypoxia in the ovine fetus
Journal of pregnancy, 2012
By late gestation, the maturing hypothalamo-pituitary-adrenal (HPA) axis aids the fetus in responding to stress. Hypoxia represents a significant threat to the fetus accompanying situations such as preeclampsia, smoking, high altitude, and preterm labor. We developed a model of high-altitude (3,820 m), long-term hypoxia (LTH) in pregnant sheep. We describe the impact of LTH on the fetal HPA axis at the level of the hypothalamic paraventricular nucleus (PVN), anterior pituitary corticotrope, and adrenal cortex. At the PVN and anterior pituitary, the responses to LTH are consistent with hypoxia being a potent activator of the HPA axis and potentially maladaptive, while the adrenocortical response to LTH appears to be primarily adaptive. We discuss mechanisms involved in the delicate balance between these seemingly opposing responses that preserve the normal ontogenic rise in fetal plasma cortisol essential for organ maturation and in this species, birth. Further, we examine the respon...