Disturbances in Maternal Steroidogenesis and Appearance of Intrauterine Growth Retardation at High-Altitude Environments Are Established from Early Pregnancy. Effects of Treatment with Antioxidant Vitamins

Abstract

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 short-term 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.

Models of Intrauterine growth restriction and fetal programming in rabbits

“…It is also a main cause of IUGR at high altitude. Whilst the impact of hypoxia on fetal growth and developmental programming has been widely studied in rodents (Aljunaidy, Morton, Cooke, & Davidge, ; Higgins, Vaughan, Fernandez de Liger, Fowden & Sferruzzi‐Perri, ; Turan, Aberdeen, & Thompson, ) and sheep (Allison et al, ; Herrera et al, ; Parraguez et al, ), few researchers have used the rabbit as an animal model. In pregnant rabbits, continuous exposure to hypobaric oxygen conditions (13.2% oxygen equivalent to 3,657 m) from GD14, decreased fetal and placental weight at GD30–31 (Chang, Rutledge, Stoops, & Abbe, ).…”

“…Hypoxia is a common feature of pathological human pregnancies at sea level and often caused by smoking, anemia, and maternal disease (Giussani, 2016 (Allison et al, 2016;Herrera et al, 2016;Parraguez et al, 2011Parraguez et al, , 2015, few researchers have used the rabbit as an animal model. In pregnant rabbits, continuous exposure to hypobaric oxygen conditions (13.2% oxygen equivalent to 3,657 m) from GD14, decreased fetal and placental weight at GD30-31 (Chang, Rutledge, Stoops, & Abbe, 1984).…”

The newborn sheep translational model for pulmonary arterial hypertension of the neonate at high altitude

“…Increased wall thickness of small pulmonary arteries Llanos et al 30 Fetal/neonatal chronic hypoxia Increased pulmonary 5HT and PDE-5. Increased NO vasodilator capacity and wall thickness in small pulmonary arteries Parraguez et al 45 Fetal chronic hypoxia Long-and short-term exposure to high-altitude causes disturbances in maternal ovarian steroidogenesis and negatively affects embryo-fetal growth Moretta et al 47 Fetal chronic hypoxia Gestational hypoxia modulates pulmonary vasoconstriction potentially through upregulation of α1-AR.…”

“…2,17,21,31,34 The sheep has been used as a model that represents an animal not adapted to high altitude, such as the human species. 21,30,[42][43][44][45][46][47][48][49] Pregnant women and their unborn babies from several regions of the world are chronically exposed to the low-oxygen milieu of high-altitude mountains or plateaus. 21,50,51 Pregnancy at high altitude is clearly a potential burden for both mother and fetus.…”

Hypoxic Stress Forces Irreversible Differentiation of a Majority of Mouse Trophoblast Stem Cells Despite FGF4

“…It can happen to pregnancies at high altitude [5] or in urban areas because of carbon monoxide (CO) pollution. CO has higher binding affinity to hemoglobin than O 2 [6].…”