Fertility in a high-altitude environment is compromised by luteal dysfunction: the relative roles of hypoxia and oxidative stress

Reproductive Biology and Endocrinology

Antonio González-Bulnes¹  Susana Astiz¹  Adriana Aguado-Martínez⁵  Laura Torres-Rovira⁴  Mónica De los Reyes³  Giorgio Castellaro²  Laura Pérez³  Bessie Urquieta³  Víctor H Parraguez⁶ 

[1] Department of Animal Reproduction, INIA, Av. Puerta de Hierro s/n, Madrid, 28040, Spain;Faculty of Agricultural Sciences, University of Chile, Casilla 2, Correo 15, La Granja, Santiago, Chile;Faculty of Veterinary Sciences, University of Chile, Casilla 2, Correo 15, La Granja, Santiago, Chile;Department of Animal Biology, University of Sassari, Via Vienna 2, Sassari, 07100, Italy;SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s/n, Madrid, 28040, Spain;International Centre for Andean Studies, University of Chile, Casilla 2, Correo 15, La Granja, Santiago, Chile

关键词: Antioxidant vitamins;    Oxidative stress;    Hypoxia;    Corpus luteum function;    Sheep;   

Others  :  812415
DOI  :  10.1186/1477-7827-11-24

 received in 2012-12-27, accepted in 2013-03-13,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Parraguez et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]Bangham CR, Sacherer JM: Fertility of Nepalese Sherpas at moderate altitudes: comparison with high-altitude data. Ann Hum Biol 1980, 7:323-330.
• [2]Parraguez VH, Atlagich M, Behn C, Bruzzone ME, Raggi LA: Fertility in ewes at high altitude: comparison between animals with long- and short-time residence at high altitude and the effect of antioxidant vitamins. Reprod Dom Anim 2006, 41:372.
• [3]De Carolis G: Descripción del sistema ganadero y hábitos alimentarios de camélidos domésticos y ovinos en el bofedal de Parinacota. Agr. Eng. Dissertation. Universidad de Chile, Facultad de Ciencias Agronómicas, Dpto. de Producción Animal; 1987.
• [4]Vitzthum VJ, Wiley AS: The proximate determinants of fertility in population exposed to chroninc hypoxia. High Alt Med Biol 2003, 4:125-139.
• [5]Huddleston B, Ataman E, de Salvo P, Zanetti M, Bloise M, Bel J, Franceschini G, Fè ďOstiani L: Towards a GIS-based analysis of mountain environments and populations. In Environment and natural resources. Working paper Nº 10. Rome, Italy: Food and Agriculture Organization of the United Nations; 2003:26.
• [6]Parraguez VH, Urquieta B, De los Reyes M, González-Bulnes A, Astiz S, Muñoz A: Steroidoenesis in sheep pregnancy with inrauterine growth retardation by high altitude hypoxia: effects of maternal altitudinal status and antioxidant treatment. Reprod Fert Devin press
• [7]Parraguez VH, Atlagich M, Araneda O, García C, Muñoz A, De los Reyes M, Urquieta B: Effects of antioxidant vitamins on newborn and placental traits in gestations at high altitude: comparative study in high and low altitude native sheep. Reprod Fertil Dev 2011, 23:285-296.
• [8]NRC: Nutrient Requirements of Sheep. 6th edition. Washington, DC: National Academy Press; 1985:45.
• [9]Reznick A, Packer L: Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 1994, 233:357-363.
• [10]Lastard M, Ljungkvist G, Olin AC, Toren K: Determination of malondialdehyde in breath condensate by high-performance liquid chromatography with fluorescence detection. J Chromatogr B Analyt Technol Biomed Life Sci 2002, 766:107-114.
• [11]Wayner DD, Burton GW, Ingold KU, Locke S: Quantitative measurement of the total, peroxyl-radical trapping antioxidant capability of human blood plasma by controlled peroxidation. FEBS Lett 1985, 187:33-37.
• [12]Lissi E, Pascual C, Del Castillo MD: Luminol luminescence induced by 2,2’-Azo-bis (2-amidinopropane) thermolisys. Free Rad Res Commun 1992, 17:299-311.
• [13]Primer3Plus. http://www.bioinformatics.nl/cgi-bin/primer3plus/primer3plus.cgi webcite
• [14]Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real- time quantitative PCR and the 2-ΔΔCt method. Methods 2001, 25:402-408.
• [15]Girish V, Vijayalakshmi A: Affordable image analysis using NIH image/ImageJ. Indian J Cancer 2004, 41:47.
• [16]Keisler DH, Keisler LW: Formation and function of GnRH induced subnormal corpora lutea in cyclic ewes. J Reprod Fertil 1989, 87:267-273.
• [17]Adams GP: Comparative patterns of follicle development and selection in ruminants. J Reprod Fertil Suppl 1999, 54:17-32.
• [18]Campbell BK, Dobson H, Baird DT, Scaramuzzi RJ: Examination of the relative role of FSH and LH in the mechanism of ovulatory follicle selection in sheep. J Reprod Fertil 1999, 117:355-367.
• [19]Escudero F, Gonzales GF, Góñez C: Hormone profile during the menstrual cycle at high altitude. Int J Gynaecol Obstet 1996, 55:49-58.
• [20]Richards JS, Russell DL, Ochsner S, Hsieh M, Doyle KH, Falender AE, Lo YK, Sharma SC: Novel signaling pathways that control ovarian follicular development, ovulation, and luteinization. Recent Prog Horm Res 2002, 57:195-220.
• [21]Webb R, Woad KJ, Armstrong DG: Corpus luteum (CL) function: local control mechanisms. Domest Anim Endocrinol 2002, 23:277-285.
• [22]Berisha B, Schams D: Ovarian function in ruminants. Domest Anim Endocrinol 2005, 29:305-317.
• [23]Zheng J, Fricke PM, Reynolds LP, Redmer DA: Evaluation of growth, cell proliferation, and cell death in bovine corpora lutea throughout the estrous cycle. Biol Reprod 1994, 51:623-632.
• [24]Schams D, Berisha B: Regulation of corpus luteum function in Cattle – an overview. Reprod Domest Anim 2004, 39:241-251.
• [25]Miyamoto A, Shirasuna K, Sasahara K: Local regulation of corpus luteum development and regression in the cow: impact of angiogenic and vasoactive factors. Domest Anim Endocrinol 2009, 37:159-169.
• [26]Nishimura R, Okuda K: Hypoxia is important for establishing vascularisation during corpus luteum formation in cattle. J Reprod Dev 2010, 56:110-116.
• [27]Tropea A, Miceli F, Minici F, Tiberi F, Orlando M, Gangale MF, Romani F, Catino S, Mancuso S, Navarra P, Lanzone A, Apa R: Regulation of vascular endothelial growth factor synthesis and release by human luteal cells in vitro. J Clin Endocrinol Metab 2006, 91:2303-2309.
• [28]Sugino N, Suzuki T, Sakata A, Miwa I, Asada H, Taketani T, Yamagata Y, Tamura H: Angiogenesis in the human corpus luteum: changes in expression of angiopoietins in the corpus luteum throughout the menstrual cycle and in early pregnancy. J Clin Endocrinol Metab 2005, 90:6141-6148.
• [29]Parraguez VH, Atlagich M, Urquieta B, Galleguillos M, De los Reyes M, Kooyman DL, Araneda S, Raggi LA: Expression of vascular endothelial growth factor and endothelial nitric oxide synthase is increased in the placenta of sheep at high altitude in the Andes. Can J Vet Res 2010, 74:193-199.
• [30]Contreras-Solis I, Diaz T, Lopez G, Caigua A, Lopez-Sebastian A, Gonzalez-Bulnes A: Systemic and intraovarian effects of corpus luteum on follicular dynamics during oestrous cycle in hair breed sheep. Anim Reprod Sci 2008, 104:47-55.
• [31]León-Velarde F, Rivera-Chira M, Tapia R, Huicho L, Monge C: Relationship of ovarian hormones to hypoxemia in women residents of 4,300 m. Am J Physiol Reg Integr Comp Physiol 2001, 280:R488-R493.
• [32]Takase K, Nishiyasu T, Asano K: Modulating effects of the menstrual cycle on cardiorespiratory responses to exercise under acute hypobaric hypoxia. Jap J Phys 2002, 52:553-560.
• [33]Niswender GD, Juengel JL, Silva PJ, Rollyson MK, McIntush EW: Mechanisms controlling the function and life span of the corpus luteum. Physiol Rev 2000, 80:1-29.
• [34]Lemley CO, Vonnahme KA, Tager LR, Krause KM, Wilson ME: Diet-induced alterations in hepatic progesterone (P4) catabolic enzyme activity and P4 clearance rate in lactating dairy cows. J Endocrinol 2010, 205:233-241.
• [35]Arena B, Maffulli N, Maffulli F, Morleo MA: Reproductive hormones and menstrual changes with exercise in female athletes. Sports Med 1995, 19:278-287.
• [36]González-Arenas A, Agramonte-Hevia J: Sex steroids hormone effects in normal and pathologic conditions in lung physiology. Mini-Rev Med Chem 2012, 11:1055-1062.
• [37]Basu M, Pal K, Prasad R, Malhotra AS, Rao KS, Sawhney RC: Pituitary, gonadal and adrenal hormones after prolonged residence at extreme altitude in man. Int J Androl 1997, 20:153-158.
• [38]Gonzalez-Bulnes A, Veiga-Lopez A, Garcia P, Garcia-Garcia RM, Ariznavarreta C, Sanchez MA, Tresguerres JA, Cocero MJ, Flores JM: Effects of progestagens and prostaglandin analogues on ovarian function and embryo viability in sheep. Theriogenology 2005, 63:2523-2534.
• [39]Nett TM: Function of the hypothalamic–hypophysial axis during the postpartum period in ewes and cows. In Reproduction in domestic ruminants. Edited by Niswender GD, Baird DT, Findlay JK, Weir BJ. Dorchester, Dorset, United Kingdom: Dorset Press; 1987:201-213.
• [40]Viñoles C, Meikle A, Forsberg M, Rubianes E: The effect of subluteal levels of exogenous progesterone on follicular dynamics and endocrine patterns during early luteal phase of the ewe. Theriogenology 1999, 51:1351-1361.