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 increased lamb birthweight and cotyledon number in both HA native and newcomer ewes, although placental weight and cotyledon surface were diminished. Placentas from vitamin-supplemented HA ewes were similar to those from ewes at sea level, making these placental traits (weight, number and diameter of cotyledons) similar to those from ewes at sea level. Vitamin supplementation had no effect on LA pregnancies. In conclusion, supplementation with vitamins C and E during pregnancy at HA prevents oxidative stress, improving pregnancy outcomes.

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The present studies assessed the effect of hypobaric hypoxia on fetal lamb growth in high-altitude (HA) and low-altitude (LA) native ewes. Growth patterns of fetal biparietal diameter (BPD), abdominal diameter (AD) and thorax height (TH) were described by consecutive ultrasound measurements throughout the entire pregnancy. Three groups of animals were used: (1) pregnant LA ewes kept at LA (control; 'LL' group); (2) pregnant LA ewes moved to HA immediately after confirmation of pregnancy ('LH' group); and (3) pregnant HA ewes kept at HA throughout the entire pregnancy ('HH' group). The slope of the BPD curve was higher in LL fetuses followed by that in LH fetuses. During the last month of pregnancy, TH was higher in LH and HH fetuses, whereas AD was higher in LL than in LH fetuses. The length of gestation was longer in HH ewes (153.2 +/- 4.3 days) than in LH and LL ewes (146.0 +/- 5.5 and 145.0 +/- 3.0 days, respectively). Bodyweight at birth was higher for LL newborns (4.2 +/- 0.3 kg) than for LH and HH newborns (3.0 +/- 0.5 and 3.2 +/- 0.8 kg, respectively), whereas placental weight was higher in the HH group (396 +/- 80 g) than in the LH (303 +/- 64 g) and LL (280 +/- 40 g) groups. In conclusion, an HA environment modifies fetal growth and pregnancy outcome with the magnitude of effects depending on the time of residence at HA.

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