title: Fertility in a high-altitude environment is compromised by luteal dysfunction: the relative roles of hypoxia and oxidative stress.
abstract: BACKGROUND
  At high altitudes, hypoxia, oxidative stress or both compromise sheep fertility. In the present work, we tested the relative effect of short- or long-term exposure to high altitude hypobaric hypoxia and oxidative stress on corpora luteal structure and function.
  
  
  METHODS
  The growth dynamics of the corpora lutea during the estrous cycle were studied daily by ultrasonography in cycling sheep that were either native or naïve to high-altitude conditions and that were supplemented or not supplemented with antioxidant vitamins. Arterial and venous blood samples were simultaneously drawn for determination of gases and oxidative stress biomarkers and progesterone measurement. On day five after ovulation in the next cycle, the ovaries were removed for immunodetection of luteal HIF-1alpha and VEGF and IGF-I and to detect IGF-II gene expression.
  
  
  RESULTS
  The results showed that both short- and long-term exposure to high-altitude conditions decreased luteal growth and IGF-I and IGF-II gene expression but increased HIF-1 alpha and VEGF immunoexpression. The level of plasma progesterone was also increased at a high altitude, although an association with increased corpus luteum vascularization was only found in sheep native to a high-altitude location. Administration of antioxidant vitamins resulted in a limited effect, which was restricted to decreased expression of oxidative stress biomarkers and luteal HIF-1alpha and VEGF immunoexpression.
  
  
  CONCLUSIONS
  Exposure of the sheep to high-altitude hypobaric hypoxia for short or long time periods affects the development and function of the corpus luteum. Moreover, the observed association of oxidative stress with hypoxia and the absence of any significant effect of antioxidant vitamins on most anatomical and functional corpus luteum traits suggests that the effects of high altitude on this ovarian structure are mainly mediated by hypoxia. Thus, these findings may help explain the decrease in sheep fertility at a high altitude.
authors.affiliation: Faculty of Veterinary Sciences, University of Chile, Casilla 2, Correo 15, La Granja, Santiago, Chile. vparragu@uchile.cl
authors.forename: Víctor H
authors.initials: VH
authors.lastname: Parraguez
authors.forename: Bessie
authors.initials: B
authors.lastname: Urquieta
authors.forename: Laura
authors.initials: L
authors.lastname: Pérez
authors.forename: Giorgio
authors.initials: G
authors.lastname: Castellaro
authors.forename: Mónica
authors.initials: M
authors.lastname: De los Reyes
authors.forename: Laura
authors.initials: L
authors.lastname: Torres-Rovira
authors.forename: Adriana
authors.initials: A
authors.lastname: Aguado-Martínez
authors.forename: Susana
authors.initials: S
authors.lastname: Astiz
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Bulnes
mesh_terms: D000531:Altitude; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D003338:Corpus Luteum / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D005298:Fertility / Q000502:physiology*; D015870:Gene Expression; D000860:Hypoxia / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D010053:Ovary / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011374:Progesterone / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D013997:Time Factors; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D014810:Vitamin E; D011374:Progesterone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D001205:Ascorbic Acid