Skip to main content
Top
Published in: Reproductive Biology and Endocrinology 1/2013

Open Access 01-12-2013 | Research

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

Authors: Víctor H Parraguez, Bessie Urquieta, Laura Pérez, Giorgio Castellaro, Mónica De los Reyes, Laura Torres-Rovira, Adriana Aguado-Martínez, Susana Astiz, Antonio González-Bulnes

Published in: Reproductive Biology and Endocrinology | Issue 1/2013

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Bangham CR, Sacherer JM: Fertility of Nepalese Sherpas at moderate altitudes: comparison with high-altitude data. Ann Hum Biol. 1980, 7: 323-330. 10.1080/03014468000004391.CrossRefPubMed Bangham CR, Sacherer JM: Fertility of Nepalese Sherpas at moderate altitudes: comparison with high-altitude data. Ann Hum Biol. 1980, 7: 323-330. 10.1080/03014468000004391.CrossRefPubMed
2.
go back to reference 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- 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.
go back to reference De Carolis G: Descripción del sistema ganadero y hábitos alimentarios de camélidos domésticos y ovinos en el bofedal de Parinacota. Agr. Eng. Dissertation. 1987, Universidad de Chile, Facultad de Ciencias Agronómicas, Dpto. de Producción Animal De Carolis G: Descripción del sistema ganadero y hábitos alimentarios de camélidos domésticos y ovinos en el bofedal de Parinacota. Agr. Eng. Dissertation. 1987, Universidad de Chile, Facultad de Ciencias Agronómicas, Dpto. de Producción Animal
4.
go back to reference Vitzthum VJ, Wiley AS: The proximate determinants of fertility in population exposed to chroninc hypoxia. High Alt Med Biol. 2003, 4: 125-139. 10.1089/152702903322022758.CrossRefPubMed Vitzthum VJ, Wiley AS: The proximate determinants of fertility in population exposed to chroninc hypoxia. High Alt Med Biol. 2003, 4: 125-139. 10.1089/152702903322022758.CrossRefPubMed
5.
go back to reference 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. Environment and natural resources. Working paper Nº 10. 2003, Rome, Italy: Food and Agriculture Organization of the United Nations, 26- 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. Environment and natural resources. Working paper Nº 10. 2003, Rome, Italy: Food and Agriculture Organization of the United Nations, 26-
6.
go back to reference 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 Dev. 10.1071/RD12020. in press 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 Dev. 10.1071/RD12020. in press
7.
go back to reference 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. 10.1071/RD10016.CrossRefPubMed 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. 10.1071/RD10016.CrossRefPubMed
8.
go back to reference NRC: Nutrient Requirements of Sheep. 1985, Washington, DC: National Academy Press, 45-6 NRC: Nutrient Requirements of Sheep. 1985, Washington, DC: National Academy Press, 45-6
9.
go back to reference Reznick A, Packer L: Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol. 1994, 233: 357-363.CrossRefPubMed Reznick A, Packer L: Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol. 1994, 233: 357-363.CrossRefPubMed
10.
go back to reference 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. 10.1016/S0378-4347(01)00437-6.CrossRef 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. 10.1016/S0378-4347(01)00437-6.CrossRef
11.
go back to reference 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. 10.1016/0014-5793(85)81208-4.CrossRefPubMed 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. 10.1016/0014-5793(85)81208-4.CrossRefPubMed
12.
go back to reference 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. 10.3109/10715769209079523.CrossRef 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. 10.3109/10715769209079523.CrossRef
14.
go back to reference 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. 10.1006/meth.2001.1262.CrossRefPubMed 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. 10.1006/meth.2001.1262.CrossRefPubMed
15.
go back to reference Girish V, Vijayalakshmi A: Affordable image analysis using NIH image/ImageJ. Indian J Cancer. 2004, 41: 47-PubMed Girish V, Vijayalakshmi A: Affordable image analysis using NIH image/ImageJ. Indian J Cancer. 2004, 41: 47-PubMed
16.
go back to reference Keisler DH, Keisler LW: Formation and function of GnRH induced subnormal corpora lutea in cyclic ewes. J Reprod Fertil. 1989, 87: 267-273. Keisler DH, Keisler LW: Formation and function of GnRH induced subnormal corpora lutea in cyclic ewes. J Reprod Fertil. 1989, 87: 267-273.
17.
go back to reference Adams GP: Comparative patterns of follicle development and selection in ruminants. J Reprod Fertil Suppl. 1999, 54: 17-32.PubMed Adams GP: Comparative patterns of follicle development and selection in ruminants. J Reprod Fertil Suppl. 1999, 54: 17-32.PubMed
18.
go back to reference 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. 10.1530/jrf.0.1170355.CrossRefPubMed 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. 10.1530/jrf.0.1170355.CrossRefPubMed
19.
go back to reference Escudero F, Gonzales GF, Góñez C: Hormone profile during the menstrual cycle at high altitude. Int J Gynaecol Obstet. 1996, 55: 49-58. 10.1016/0020-7292(96)02697-5.CrossRefPubMed Escudero F, Gonzales GF, Góñez C: Hormone profile during the menstrual cycle at high altitude. Int J Gynaecol Obstet. 1996, 55: 49-58. 10.1016/0020-7292(96)02697-5.CrossRefPubMed
20.
go back to reference 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. 10.1210/rp.57.1.195.CrossRefPubMed 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. 10.1210/rp.57.1.195.CrossRefPubMed
21.
go back to reference Webb R, Woad KJ, Armstrong DG: Corpus luteum (CL) function: local control mechanisms. Domest Anim Endocrinol. 2002, 23: 277-285. 10.1016/S0739-7240(02)00163-7.CrossRefPubMed Webb R, Woad KJ, Armstrong DG: Corpus luteum (CL) function: local control mechanisms. Domest Anim Endocrinol. 2002, 23: 277-285. 10.1016/S0739-7240(02)00163-7.CrossRefPubMed
22.
go back to reference Berisha B, Schams D: Ovarian function in ruminants. Domest Anim Endocrinol. 2005, 29: 305-317. 10.1016/j.domaniend.2005.02.035.CrossRefPubMed Berisha B, Schams D: Ovarian function in ruminants. Domest Anim Endocrinol. 2005, 29: 305-317. 10.1016/j.domaniend.2005.02.035.CrossRefPubMed
23.
go back to reference 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. 10.1095/biolreprod51.4.623.CrossRefPubMed 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. 10.1095/biolreprod51.4.623.CrossRefPubMed
24.
go back to reference Schams D, Berisha B: Regulation of corpus luteum function in Cattle – an overview. Reprod Domest Anim. 2004, 39: 241-251. 10.1111/j.1439-0531.2004.00509.x.CrossRefPubMed Schams D, Berisha B: Regulation of corpus luteum function in Cattle – an overview. Reprod Domest Anim. 2004, 39: 241-251. 10.1111/j.1439-0531.2004.00509.x.CrossRefPubMed
25.
go back to reference 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. 10.1016/j.domaniend.2009.04.005.CrossRefPubMed 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. 10.1016/j.domaniend.2009.04.005.CrossRefPubMed
26.
go back to reference Nishimura R, Okuda K: Hypoxia is important for establishing vascularisation during corpus luteum formation in cattle. J Reprod Dev. 2010, 56: 110-116. 10.1262/jrd.09-162E.CrossRefPubMed Nishimura R, Okuda K: Hypoxia is important for establishing vascularisation during corpus luteum formation in cattle. J Reprod Dev. 2010, 56: 110-116. 10.1262/jrd.09-162E.CrossRefPubMed
27.
go back to reference 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. 10.1210/jc.2005-2457.CrossRefPubMed 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. 10.1210/jc.2005-2457.CrossRefPubMed
28.
go back to reference 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. 10.1210/jc.2005-0643.CrossRefPubMed 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. 10.1210/jc.2005-0643.CrossRefPubMed
29.
go back to reference 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.PubMedCentralPubMed 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.PubMedCentralPubMed
30.
go back to reference 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. 10.1016/j.anireprosci.2007.01.021.CrossRefPubMed 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. 10.1016/j.anireprosci.2007.01.021.CrossRefPubMed
31.
go back to reference 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. 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.
go back to reference 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. 10.2170/jjphysiol.52.553.CrossRef 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. 10.2170/jjphysiol.52.553.CrossRef
33.
go back to reference 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.PubMed 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.PubMed
34.
go back to reference 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. 10.1677/JOE-10-0042.CrossRefPubMed 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. 10.1677/JOE-10-0042.CrossRefPubMed
35.
go back to reference Arena B, Maffulli N, Maffulli F, Morleo MA: Reproductive hormones and menstrual changes with exercise in female athletes. Sports Med. 1995, 19: 278-287. 10.2165/00007256-199519040-00005.CrossRefPubMed Arena B, Maffulli N, Maffulli F, Morleo MA: Reproductive hormones and menstrual changes with exercise in female athletes. Sports Med. 1995, 19: 278-287. 10.2165/00007256-199519040-00005.CrossRefPubMed
36.
go back to reference 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.CrossRef 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.CrossRef
37.
go back to reference 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. 10.1046/j.1365-2605.1997.00046.x.CrossRefPubMed 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. 10.1046/j.1365-2605.1997.00046.x.CrossRefPubMed
38.
go back to reference 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. 10.1016/j.theriogenology.2004.10.013.CrossRefPubMed 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. 10.1016/j.theriogenology.2004.10.013.CrossRefPubMed
39.
go back to reference Nett TM: Function of the hypothalamic–hypophysial axis during the postpartum period in ewes and cows. Reproduction in domestic ruminants. Edited by: Niswender GD, Baird DT, Findlay JK, Weir BJ. 1987, Dorchester, Dorset, United Kingdom: Dorset Press, 201-213. Nett TM: Function of the hypothalamic–hypophysial axis during the postpartum period in ewes and cows. Reproduction in domestic ruminants. Edited by: Niswender GD, Baird DT, Findlay JK, Weir BJ. 1987, Dorchester, Dorset, United Kingdom: Dorset Press, 201-213.
40.
go back to reference 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. 10.1016/S0093-691X(99)00079-5.CrossRefPubMed 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. 10.1016/S0093-691X(99)00079-5.CrossRefPubMed
Metadata
Title
Fertility in a high-altitude environment is compromised by luteal dysfunction: the relative roles of hypoxia and oxidative stress
Authors
Víctor H Parraguez
Bessie Urquieta
Laura Pérez
Giorgio Castellaro
Mónica De los Reyes
Laura Torres-Rovira
Adriana Aguado-Martínez
Susana Astiz
Antonio González-Bulnes
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2013
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-11-24

Other articles of this Issue 1/2013

Reproductive Biology and Endocrinology 1/2013 Go to the issue