Mechanisms for rescue of corpus luteum during pregnancy: gene expression in bovine corpus luteum following intrauterine pulses of prostaglandins E1 and F2α
In ruminants, uterine pulses of prostaglandin (PG) F2α characterize luteolysis, while increased PGE2/PGE1 distinguish early pregnancy. This study evaluated intrauterine (IU) infusions of PGF2α and PGE1 pulses on corpus luteum (CL) function and gene expression. Cows on day 10 of estrous cycle receive...
- Autores:
-
Baez, Giovanni
Ochoa, Julian
Peñagaricano, Francisco
Melo, Leonardo
Lemos Motta, Jessica Cristina
Garcia Guerra, Alvaro
Meidan, Rina
Pinheiro Ferreira, João Carlos
Sartori, Roberto
Wiltbank, Milo
- Tipo de recurso:
- Article of journal
- Fecha de publicación:
- 2017
- Institución:
- Universidad Francisco de Paula Santander
- Repositorio:
- Repositorio Digital UFPS
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.ufps.edu.co:ufps/591
- Acceso en línea:
- http://repositorio.ufps.edu.co/handle/ufps/591
- Palabra clave:
- Corpus luteum
luteolysis
prostaglandin F2α
prostaglandin E1
- Rights
- openAccess
- License
- http://purl.org/coar/access_right/c_abf2
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Mechanisms for rescue of corpus luteum during pregnancy: gene expression in bovine corpus luteum following intrauterine pulses of prostaglandins E1 and F2α |
| title |
Mechanisms for rescue of corpus luteum during pregnancy: gene expression in bovine corpus luteum following intrauterine pulses of prostaglandins E1 and F2α |
| spellingShingle |
Mechanisms for rescue of corpus luteum during pregnancy: gene expression in bovine corpus luteum following intrauterine pulses of prostaglandins E1 and F2α Corpus luteum luteolysis prostaglandin F2α prostaglandin E1 |
| title_short |
Mechanisms for rescue of corpus luteum during pregnancy: gene expression in bovine corpus luteum following intrauterine pulses of prostaglandins E1 and F2α |
| title_full |
Mechanisms for rescue of corpus luteum during pregnancy: gene expression in bovine corpus luteum following intrauterine pulses of prostaglandins E1 and F2α |
| title_fullStr |
Mechanisms for rescue of corpus luteum during pregnancy: gene expression in bovine corpus luteum following intrauterine pulses of prostaglandins E1 and F2α |
| title_full_unstemmed |
Mechanisms for rescue of corpus luteum during pregnancy: gene expression in bovine corpus luteum following intrauterine pulses of prostaglandins E1 and F2α |
| title_sort |
Mechanisms for rescue of corpus luteum during pregnancy: gene expression in bovine corpus luteum following intrauterine pulses of prostaglandins E1 and F2α |
| dc.creator.fl_str_mv |
Baez, Giovanni Ochoa, Julian Peñagaricano, Francisco Melo, Leonardo Lemos Motta, Jessica Cristina Garcia Guerra, Alvaro Meidan, Rina Pinheiro Ferreira, João Carlos Sartori, Roberto Wiltbank, Milo |
| dc.contributor.author.none.fl_str_mv |
Baez, Giovanni Ochoa, Julian Peñagaricano, Francisco Melo, Leonardo Lemos Motta, Jessica Cristina Garcia Guerra, Alvaro Meidan, Rina Pinheiro Ferreira, João Carlos Sartori, Roberto Wiltbank, Milo |
| dc.subject.proposal.eng.fl_str_mv |
Corpus luteum luteolysis prostaglandin F2α prostaglandin E1 |
| topic |
Corpus luteum luteolysis prostaglandin F2α prostaglandin E1 |
| description |
In ruminants, uterine pulses of prostaglandin (PG) F2α characterize luteolysis, while increased PGE2/PGE1 distinguish early pregnancy. This study evaluated intrauterine (IU) infusions of PGF2α and PGE1 pulses on corpus luteum (CL) function and gene expression. Cows on day 10 of estrous cycle received 4 IU infusions (every 6 h; n = 5/treatment) of saline, PGE1 (2 mg PGE1), PGF2α (0.25 mg PGF2α), or PGE1 + PGF2α. A luteal biopsy was collected at 30 min after third infusion for determination of gene expression by RNA-Seq. As expected, IU pulses of PGF2α decreased (P < 0.01) P4 luteal volume. However, there were no differences in circulating P4 or luteal volume between saline, PGE1, and PGE1 + PGF2α, indicating inhibition of PGF2α-induced luteolysis by IU pulses of PGE1. After third pulse of PGF2α, luteal expression of 955 genes were altered (false discovery rate [FDR] < 0.01), representing both typical and novel luteolytic transcriptomic changes. Surprisingly, after third pulse of PGE1 or PGE1 + PGF2α, there were no significant changes in luteal gene expression (FDR > 0.10) compared to saline cows. Increased circulating concentrations of the metabolite of PGF2α (PGFM; after PGF2α and PGE1 + PGF2α) and the metabolite PGE (PGEM; after PGE1 and PGE1 + PGF2α) demonstrated that PGF2α and PGE1 are entering bloodstream after IU infusions. Thus, IU pulses of PGF2α and PGE1 allow determination of changes in luteal gene expression that could be relevant to understanding luteolysis and pregnancy. Unexpectedly, by third pulse of PGE1, there is complete blockade of either PGF2α transport to the CL or PGF2α action by PGE1 resulting in complete inhibition of transcriptomic changes following IU PGF2α pulses. |
| publishDate |
2017 |
| dc.date.issued.none.fl_str_mv |
2017-12-27 |
| dc.date.accessioned.none.fl_str_mv |
2021-11-02T14:41:53Z |
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2021-11-02T14:41:53Z |
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Artículo de revista |
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http://purl.org/coar/version/c_970fb48d4fbd8a85 |
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http://repositorio.ufps.edu.co/handle/ufps/591 |
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10.1093/biolre/iox183 |
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http://repositorio.ufps.edu.co/handle/ufps/591 |
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10.1093/biolre/iox183 |
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eng |
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eng |
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Biology of Reproduction ISSN: 0006-3363, 2018 vol:98 fasc: 4 págs: 465 - 479, DOI:10.1093/biolre/iox183 |
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Vol. 98, No. 4 (2018) |
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479 |
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4 (2018) |
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465 |
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98 |
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Julian C Ochoa, Francisco Peñagaricano, Giovanni M Baez, Leonardo F Melo, Jessica C L Motta, Alvaro Garcia-Guerra, Rina Meidan, João C Pinheiro Ferreira, Roberto Sartori, Milo C Wiltbank, Mechanisms for rescue of corpus luteum during pregnancy: gene expression in bovine corpus luteum following intrauterine pulses of prostaglandins E1 and F2α, Biology of Reproduction, Volume 98, Issue 4, April 2018, Pages 465–479, https://doi.org/10.1093/biolre/iox183 |
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Biology of Reproduction |
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15 páginas |
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Biology of Reproduction |
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Estados Unidos |
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https://academic.oup.com/biolreprod/article/98/4/465/4780269 |
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Baez, Giovannib18821a2a726f7505ba690b97bd8ba58600Ochoa, Julian03a631540c01dea9b667bffd5b35f605Peñagaricano, Francisco785bb92b090ff8da819f92a11c4b8ee7600Melo, Leonardofb929d0416d852ce3abcecdc82b3457bLemos Motta, Jessica Cristinaed9105fcbab35fa0fd3cf2cab60b3462600Garcia Guerra, Alvaro630fbc1ccf3770d19017048d54c4367b600Meidan, Rina9c36a733a15c2d31a55670a5a6d2cea7Pinheiro Ferreira, João Carlos845d5064c3e69eeb99ebb8f34f4de31a600Sartori, Roberto44014d52776f85f225b748f1818161ebWiltbank, Miloc357466f3c3066f43fa100984cf5f45f2021-11-02T14:41:53Z2021-11-02T14:41:53Z2017-12-27http://repositorio.ufps.edu.co/handle/ufps/59110.1093/biolre/iox183In ruminants, uterine pulses of prostaglandin (PG) F2α characterize luteolysis, while increased PGE2/PGE1 distinguish early pregnancy. This study evaluated intrauterine (IU) infusions of PGF2α and PGE1 pulses on corpus luteum (CL) function and gene expression. Cows on day 10 of estrous cycle received 4 IU infusions (every 6 h; n = 5/treatment) of saline, PGE1 (2 mg PGE1), PGF2α (0.25 mg PGF2α), or PGE1 + PGF2α. A luteal biopsy was collected at 30 min after third infusion for determination of gene expression by RNA-Seq. As expected, IU pulses of PGF2α decreased (P < 0.01) P4 luteal volume. However, there were no differences in circulating P4 or luteal volume between saline, PGE1, and PGE1 + PGF2α, indicating inhibition of PGF2α-induced luteolysis by IU pulses of PGE1. After third pulse of PGF2α, luteal expression of 955 genes were altered (false discovery rate [FDR] < 0.01), representing both typical and novel luteolytic transcriptomic changes. Surprisingly, after third pulse of PGE1 or PGE1 + PGF2α, there were no significant changes in luteal gene expression (FDR > 0.10) compared to saline cows. Increased circulating concentrations of the metabolite of PGF2α (PGFM; after PGF2α and PGE1 + PGF2α) and the metabolite PGE (PGEM; after PGE1 and PGE1 + PGF2α) demonstrated that PGF2α and PGE1 are entering bloodstream after IU infusions. Thus, IU pulses of PGF2α and PGE1 allow determination of changes in luteal gene expression that could be relevant to understanding luteolysis and pregnancy. Unexpectedly, by third pulse of PGE1, there is complete blockade of either PGF2α transport to the CL or PGF2α action by PGE1 resulting in complete inhibition of transcriptomic changes following IU PGF2α pulses.15 páginasapplication/pdfengBiology of ReproductionEstados UnidosBiology of Reproduction ISSN: 0006-3363, 2018 vol:98 fasc: 4 págs: 465 - 479, DOI:10.1093/biolre/iox183Vol. 98, No. 4 (2018)4794 (2018)46598Julian C Ochoa, Francisco Peñagaricano, Giovanni M Baez, Leonardo F Melo, Jessica C L Motta, Alvaro Garcia-Guerra, Rina Meidan, João C Pinheiro Ferreira, Roberto Sartori, Milo C Wiltbank, Mechanisms for rescue of corpus luteum during pregnancy: gene expression in bovine corpus luteum following intrauterine pulses of prostaglandins E1 and F2α, Biology of Reproduction, Volume 98, Issue 4, April 2018, Pages 465–479, https://doi.org/10.1093/biolre/iox183Biology of ReproductionThe Author(s) 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.cominfo:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2https://academic.oup.com/biolreprod/article/98/4/465/4780269Mechanisms for rescue of corpus luteum during pregnancy: gene expression in bovine corpus luteum following intrauterine pulses of prostaglandins E1 and F2αArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1Textinfo:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/version/c_970fb48d4fbd8a85Corpus luteumluteolysisprostaglandin F2αprostaglandin E1McCracken J, Carlson J, Glew M, Goding J, Baird D, Green K, Samuelsson B. Prostaglandin F2α identified as a luteolytic hormone in sheep. Nature 1972; 238:129–134.Northey DL, French LR. Effect of embryo removal and intrauterine infusion of embryonic homogenates on the lifespan of the bovine corpus luteum J Anim Sci 1980; 50:298–302.Spencer TE, Mirando MA, Mayes JS, Watson GH, Ott TL, Bazer FW. Effects of interferon-tau and progesterone on oestrogen-stimulated expression of receptors for oestrogen, progesterone and oxytocin in the endometrium of ovariectomized ewes. Reprod Fertil Dev 1996; 8: 843–853.Bazer FW, Song G, Thatcher WW. Roles of Conceptus secretory proteins in establishment and maintenance of pregnancy in ruminants. Asian Australas J Anim Sci 2012; 25:1–16.Dorniak P, Bazer FW, Spencer TE. Physiology and endocrinology symposium: biological role of interferon tau in endometrial function and conceptus elongation. J Anim Sci 2013; 91:1627–1638.Oliveira JF, Henkes LE, Ashley RL, Purcell SH, Smirnova NP, Veeramachaneni DN, Anthony RV, Hansen TR. Expression of interferon (IFN)- stimulated genes in extrauterine tissues during early pregnancy in sheep is the consequence of endocrine IFN-tau release from the uterine vein. Endocrinology 2008; 149:1252–1259Hansen TR, Romero JJ, Antoniazzi AQ, Bott RC, Ashley RL, Webb BT, Henkes LE, Smirnova NP. Endocrine conceptus signaling in ruminants. Anim Reprod 2013; 10:311–321.Arosh JA, Banu SK, Kimmins S, Chapdelaine P, MacLaren LA, Fortier MA. Effect of Interferon-pi on prostaglandin biosynthesis, transport, andsignaling at the time of maternal recognition of pregnancy in cattle: evidence of polycrine actions of prostaglandin E-2. Endocrinology 2004; 145:5280–5293.Lee J, McCracken JA, Stanley JA, Nithy TK, Banu SK, Arosh JA. Intraluteal prostaglandin biosynthesis and signaling are selectively directed towards PGF2alpha during luteolysis but towards PGE2 during the establishment of pregnancy in Sheep. Biol Reprod 2012; 87:97.Arosh JA, Lee J, Stephen SD, Stanley JA, Yang B, Nithy TK, Banu SK, McCracken JA. Intrauterine infusion of interferon tau selectively directs intraluteal prostaglandin biosynthesis towards PGE2 and activates EP2 and EP4-mediated signaling in the corpus luteum at the time of establishment of pregnancy in ruminants. Biol Reprod 2011; 85:S1.Ellinwood W, Nett T, Niswender G. Maintenance of the corpus luteum of early pregnancy in the Ewe. II. Prostaglandin secretion by the endometrium in vitro and in vivo. Biol Reprod 1979; 21:845–856.Huie JM, Magness RR, Reynolds LP, Hoyer G, Huecksteadt T, Colcord M, Stalcup B, Whysong GL, Weems CW. Effect of chronic ipsilateral or contralateral intra-uterine infusion of prostaglandin E1 (PGE1) on luteal function of unilaterally ovariectomized ewes. Prostaglandins 1981; 21:945–955.Weems YS, Arreguin-Arevalo JA, Nett TM, Vann RC, Ford SP, Bridges PJ, Welsh TH, Lewis AW, Neuendorff DA, Randel RD, Weems CW. In vivo intra-luteal implants of prostaglandin (PG) E1 or E2 (PGE1, PGE2) prevent luteolysis in cows. I. Luteal weight, circulating progesterone, mRNA for luteal luteinizing hormone (LH) receptor, and occupied and unoccupied luteal receptors for LH. Prostaglandins Other Lipid Mediat 2011; 95:35–44.Weems CW, Weems YS, Randel RD. Prostaglandins and reproduction in female farm animals. Vet J 2006; 171:206–228.Diez E, Chilton F, Stroup G, Mayer R, Winkler J, Fonteh A. Fatty acid and phospholipid selectivity of different phospholipase A2 enzymes studied by using a mammalian membrane as substrate. Biochem J 1994; 301:721– 726.Bonney R, Qizilbash S, Franks S. Endometrial phospholipase A2 enzymes and their regulation by steroid hormones. J Steroid Biochem 1987; 27:1057–1064.Hansen W, Keelan J, Skinner S, Mitchell M. Key enzymes of prostaglandin biosynthesis and metabolism. Coordinate regulation of expression by cytokines in gestational tissues: a review. Prostaglandins Other Lipid Mediat 1999; 57:243–257.Park JY, Pillinger MH, Abramson SB. Prostaglandin E2 synthesis and secretion: the role of PGE2 synthases. Clin Immunol 2006; 119:229–240.Stables MJ, Gilroy DW. Old and new generation lipid mediators in acute inflammation and resolution. Prog Lipid Res 2011; 50:35–51.Smith WL, Dewitt DL. Prostaglandin endoperoxide H synthases-1 and-2. Adv Immunol 1996; 62:167–216.Anderson LE, Wu YL, Tsai SJ, Wiltbank MC. Prostaglandin F2 alpha receptor in the corpus luteum: recent information on the gene, messenger ribonucleic acid, and protein. Biol Reprod 2001; 64:1041–1047.Parker I, Ivorra I. Localized all-or-none calcium liberation by inositol trisphosphate. Science 1990; 250:977–979.Hoyer P, Marion S. Influence of agents that affect intracellular calcium regulation on progesterone secretion in small and large luteal cells of the sheep. Reproduction 1989; 86:445–455.Mart´ınez-Zaguilan R, Wegner JA, Gillies RJ, Hoyer PB. Differential reg- ´ ulation of Ca2+ homeostasis in ovine large and small luteal cells. Endocrinology 1994; 135:2099–2108.Wiltbank M, Diskin M, Niswender G. Differential actions of second messenger systems in the corpus luteum. J Reprod Fertil Suppl 1990; 43: 65–75.Davis JS, Weakland LL, Weiland DA, Farese RV, West LA. Prostaglandin F2 alpha stimulates phosphatidylinositol 4,5-bisphosphate hydrolysis and mobilizes intracellular Ca2+ in bovine luteal cells. Proc Natl Acad Sci 1987; 84:3728–3732.Goupil E, Tassy D, Bourguet C, Quiniou C, Wisehart V, Petrin D, Le Gouill C, Devost D, Zingg HH, Bouvier M, Saragovi HU, Chemtob S et al. A novel biased allosteric compound inhibitor of parturition selectively impedes the prostaglandin F2 alpha-mediated Rho/ROCK signaling pathway. J Biol Chem 2010; 285:25624–25636.Narumiya S, FitzGerald GA. Genetic and pharmacological analysis of prostanoid receptor function. J Clin Invest 2001; 108:25–30.Narumiya S, Sugimoto Y, Ushikubi F. 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Acta Endocrinol 1976; 82:134–149.Mann GE, Lamming GE. Timing of prostaglandin F2 alpha release episodes and oxytocin receptor development during luteolysis in the cow. Anim Reprod Sci 2006; 93:328–336.Ginther OJ, Araujo RR, Palhao MP, Rodrigues BL, Beg MA. Necessity of sequential pulses of prostaglandin F2alpha for complete physiologic luteolysis in cattle. Biol Reprod 2009; 80:641–648.Atli MO, Bender RW, Mehta V, Bastos MR, Luo WX, Vezina CM, Wiltbank MC. Patterns of gene expression in the bovine corpus luteum following repeated intrauterine infusions of low doses of prostaglandin F2alpha. Biol Reprod 2012; 86:130.Mondal M, Schilling B, Folger J, Steibel JP, Buchnick H, Zalman Y, Ireland JJ, Meidan R, Smith GW. Deciphering the luteal transcriptome: potential mechanisms mediating stage-specific luteolytic response of the corpus luteum to prostaglandin F-2 alpha. Physiol Genom 2011; 43: 447–456.Smith GW, Meidan R. Ever-changing cell interactions during the life span of the corpus luteum: relevance to luteal regression Reprod Biol 2014; 14:75–82.Fields M, Fields P. Morphological characteristics of the bovine corpus luteum during the estrous cycle and pregnancy. Theriogenology 1996; 45:1295–1325.Mann G, Lamming G, Fray M. Plasma oestradiol and progesterone during early pregnancy in the cow and the effects of treatment with buserelin. Anim Reprod Sci 1995; 37:121–131.Grygar I, Kudla´ c E, Dole ˇ zel R, Nedb ˇ alkov ´ a J. Volume of luteal tissue and ´ concentration of serum progesterone in cows bearing homogeneous corpus luteum or corpus luteum with cavity. Anim Reprod Sci 1997; 49:77–82.Mapletoft RJ, Lapin DR, Ginther OJ. The ovarian artery as the final component of the local luteotropic pathway between a gravid uterine horn and ovary in ewes. Biol Reprod 1976; 15:414–421.Mapletoft RJ, Delcampo MR, Ginther OJ. Unilateral luteotropic effect of uterine venous effluent of a gravid uterine horn in sheep. Exp Biol Med 1975; 150:129–133.Arosh JA, Banu SK, McCracken JA. Novel concepts on the role of prostaglandins on luteal maintenance and maternal recognition and establishment of pregnancy in ruminants. J Dairy Sci 2016; 99: 5926–5940.DanetDesnoyers G, Meyer MD, Gross TS, Johnson JW, Thatcher WW. Regulation of endometrial prostaglandin synthesis during early pregnancy in cattle: Effects of phospholipases and calcium in vitro. Prostaglandins 1995; 50:313–330.Arnold DR, Binelli M, Vonk J, Alexenko AP, Drost M, Wilcox CJ, Thatcher WW. Intracellular regulation of endometrial PGF(2a) and PGE(2) production in dairy cows during early pregnancy and following treatment with recombinant interferon-tau. Domest Anim Endocrinol 2000; 18:199–216.Charpigny G, Reinaud P, Tamby J-P, Creminon C, Guillomot M. 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Biol Reprod 2012; 86:1–10.ORIGINALMechanisms for rescue of corpus luteum during pregnancy gene expression in bovine corpus luteum following intrauterine pulses of prostaglandins E1 and F2α.pdfMechanisms for rescue of corpus luteum during pregnancy gene expression in bovine corpus luteum following intrauterine pulses of prostaglandins E1 and F2α.pdfapplication/pdf2002791https://repositorio.ufps.edu.co/bitstream/ufps/591/1/Mechanisms%20for%20rescue%20of%20corpus%20luteum%20during%20pregnancy%20gene%20expression%20in%20bovine%20corpus%20luteum%20following%20intrauterine%20pulses%20of%20prostaglandins%20E1%20and%20F2%ce%b1.pdf6479a24a73ec099484e7a3d8d286db01MD51metadata only accessLICENSElicense.txtlicense.txttext/plain; charset=utf-814828https://repositorio.ufps.edu.co/bitstream/ufps/591/2/license.txt2f9959eaf5b71fae44bbf9ec84150c7aMD52open accessTEXTMechanisms for rescue of corpus luteum during pregnancy gene expression in bovine corpus luteum following intrauterine pulses of 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Thumbnailimage/jpeg15649https://repositorio.ufps.edu.co/bitstream/ufps/591/4/Mechanisms%20for%20rescue%20of%20corpus%20luteum%20during%20pregnancy%20gene%20expression%20in%20bovine%20corpus%20luteum%20following%20intrauterine%20pulses%20of%20prostaglandins%20E1%20and%20F2%ce%b1.pdf.jpg7479851d816d1dca21adfba4a1272e65MD54metadata only accessufps/591oai:repositorio.ufps.edu.co:ufps/5912022-05-23 11:01:02.255metadata only accessRepositorio Universidad Francisco de Paula 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 incorporada en las Obras Colectivas.

b.	Distribuir copias o fonogramas de las Obras, exhibirlas públicamente, ejecutarlas públicamente y/o ponerlas a disposición pública, incluyéndolas como incorporadas en Obras Colectivas, según corresponda.

c.	Distribuir copias de las Obras Derivadas que se generen, exhibirlas públicamente, ejecutarlas públicamente y/o ponerlas a disposición pública.
Los derechos mencionados anteriormente pueden ser ejercidos en todos los medios y formatos, actualmente conocidos o que se inventen en el futuro. Los derechos antes mencionados incluyen el derecho a realizar dichas modificaciones en la medida que sean técnicamente necesarias para ejercer los derechos en otro medio o formatos, pero de otra manera usted no está autorizado para realizar obras derivadas. Todos los derechos no otorgados expresamente por el Licenciante quedan por este medio reservados, incluyendo pero sin limitarse a aquellos que se mencionan en las secciones 4(d) y 4(e).

4. Restricciones.
La licencia otorgada en la anterior Sección 3 está expresamente sujeta y limitada por las siguientes restricciones:

a.	Usted puede distribuir, exhibir públicamente, ejecutar públicamente, o poner a disposición pública la Obra sólo bajo las condiciones de esta Licencia, y Usted debe incluir una copia de esta licencia o del Identificador Universal de Recursos de la misma con cada copia de la Obra que distribuya, exhiba públicamente, ejecute públicamente o ponga a disposición pública. No es posible ofrecer o imponer ninguna condición sobre la Obra que altere o limite las condiciones de esta Licencia o el ejercicio de los derechos de los destinatarios otorgados en este documento. No es posible sublicenciar la Obra. Usted debe mantener intactos todos los avisos que hagan referencia a esta Licencia y a la cláusula de limitación de garantías. Usted no puede distribuir, exhibir públicamente, ejecutar públicamente, o poner a disposición pública la Obra con alguna medida tecnológica que controle el acceso o la utilización de ella de una forma que sea inconsistente con las condiciones de esta Licencia. Lo anterior se aplica a la Obra incorporada a una Obra Colectiva, pero esto no exige que la Obra Colectiva aparte de la obra misma quede sujeta a las condiciones de esta Licencia. Si Usted crea una Obra Colectiva, previo aviso de cualquier Licenciante debe, en la medida de lo posible, eliminar de la Obra Colectiva cualquier referencia a dicho Licenciante o al Autor Original, según lo solicitado por el Licenciante y conforme lo exige la cláusula 4(c).

b.	Usted no puede ejercer ninguno de los derechos que le han sido otorgados en la Sección 3 precedente de modo que estén principalmente destinados o directamente dirigidos a conseguir un provecho comercial o una compensación monetaria privada. El intercambio de la Obra por otras obras protegidas por derechos de autor, ya sea a través de un sistema para compartir archivos digitales (digital file-sharing) o de cualquier otra manera no será considerado como estar destinado principalmente o dirigido directamente a conseguir un provecho comercial o una compensación monetaria privada, siempre que no se realice un pago mediante una compensación monetaria en relación con el intercambio de obras protegidas por el derecho de autor.

c.	Si usted distribuye, exhibe públicamente, ejecuta públicamente o ejecuta públicamente en forma digital la Obra o cualquier Obra Derivada u Obra Colectiva, Usted debe mantener intacta toda la información de derecho de autor de la Obra y proporcionar, de forma razonable según el medio o manera que Usted esté utilizando: (i) el nombre del Autor Original si está provisto (o seudónimo, si fuere aplicable), y/o (ii) el nombre de la parte o las partes que el Autor Original y/o el Licenciante hubieren designado para la atribución (v.g., un instituto patrocinador, editorial, publicación) en la información de los derechos de autor del Licenciante, términos de servicios o de otras formas razonables; el título de la Obra si está provisto; en la medida de lo razonablemente factible y, si está provisto, el Identificador Uniforme de Recursos (Uniform Resource Identifier) que el Licenciante especifica para ser asociado con la Obra, salvo que tal URI no se refiera a la nota sobre los derechos de autor o a la información sobre el licenciamiento de la Obra; y en el caso de una Obra Derivada, atribuir el crédito identificando el uso de la Obra en la Obra Derivada (v.g., "Traducción Francesa de la Obra del Autor Original," o "Guión Cinematográfico basado en la Obra original del Autor Original"). Tal crédito puede ser implementado de cualquier forma razonable; en el caso, sin embargo, de Obras Derivadas u Obras Colectivas, tal crédito aparecerá, como mínimo, donde aparece el crédito de cualquier otro autor comparable y de una manera, al menos, tan destacada como el crédito de otro autor comparable.

d.	Para evitar toda confusión, el Licenciante aclara que, cuando la obra es una composición musical:

i.	Regalías por interpretación y ejecución bajo licencias generales. El Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública o la ejecución pública digital de la obra y de recolectar, sea individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, SAYCO), las regalías por la ejecución pública o por la ejecución pública digital de la obra (por ejemplo Webcast) licenciada bajo licencias generales, si la interpretación o ejecución de la obra está primordialmente orientada por o dirigida a la obtención de una ventaja comercial o una compensación monetaria privada.

ii.	Regalías por Fonogramas. El Licenciante se reserva el derecho exclusivo de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, los consagrados por la SAYCO), una agencia de derechos musicales o algún agente designado, las regalías por cualquier fonograma que Usted cree a partir de la obra (“versión cover”) y distribuya, en los términos del régimen de derechos de autor, si la creación o distribución de esa versión cover está primordialmente destinada o dirigida a obtener una ventaja comercial o una compensación monetaria privada.

e.	Gestión de Derechos de Autor sobre Interpretaciones y Ejecuciones Digitales (WebCasting). Para evitar toda confusión, el Licenciante aclara que, cuando la obra sea un fonograma, el Licenciante se reserva el derecho exclusivo de autorizar la ejecución pública digital de la obra (por ejemplo, webcast) y de recolectar, individualmente o a través de una sociedad de gestión colectiva de derechos de autor y derechos conexos (por ejemplo, ACINPRO), las regalías por la ejecución pública digital de la obra (por ejemplo, webcast), sujeta a las disposiciones aplicables del régimen de Derecho de Autor, si esta ejecución pública digital está primordialmente dirigida a obtener una ventaja comercial o una compensación monetaria privada.

5. Representaciones, Garantías y Limitaciones de Responsabilidad.
A MENOS QUE LAS PARTES LO ACORDARAN DE OTRA FORMA POR ESCRITO, EL LICENCIANTE OFRECE LA OBRA (EN EL ESTADO EN EL QUE SE ENCUENTRA) “TAL CUAL”, SIN BRINDAR GARANTÍAS DE CLASE ALGUNA RESPECTO DE LA OBRA, YA SEA EXPRESA, IMPLÍCITA, LEGAL O CUALQUIERA OTRA, INCLUYENDO, SIN LIMITARSE A ELLAS, GARANTÍAS DE TITULARIDAD, COMERCIABILIDAD, ADAPTABILIDAD O ADECUACIÓN A PROPÓSITO DETERMINADO, AUSENCIA DE INFRACCIÓN, DE AUSENCIA DE DEFECTOS LATENTES O DE OTRO TIPO, O LA PRESENCIA O AUSENCIA DE ERRORES, SEAN O NO DESCUBRIBLES (PUEDAN O NO SER ESTOS DESCUBIERTOS). ALGUNAS JURISDICCIONES NO PERMITEN LA EXCLUSIÓN DE GARANTÍAS IMPLÍCITAS, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.

6. Limitación de responsabilidad.
A MENOS QUE LO EXIJA EXPRESAMENTE LA LEY APLICABLE, EL LICENCIANTE NO SERÁ RESPONSABLE ANTE USTED POR DAÑO ALGUNO, SEA POR RESPONSABILIDAD EXTRACONTRACTUAL, PRECONTRACTUAL O CONTRACTUAL, OBJETIVA O SUBJETIVA, SE TRATE DE DAÑOS MORALES O PATRIMONIALES, DIRECTOS O INDIRECTOS, PREVISTOS O IMPREVISTOS PRODUCIDOS POR EL USO DE ESTA LICENCIA O DE LA OBRA, AUN CUANDO EL LICENCIANTE HAYA SIDO ADVERTIDO DE LA POSIBILIDAD DE DICHOS DAÑOS. ALGUNAS LEYES NO PERMITEN LA EXCLUSIÓN DE CIERTA RESPONSABILIDAD, EN CUYO CASO ESTA EXCLUSIÓN PUEDE NO APLICARSE A USTED.

7. Término.

a.	Esta Licencia y los derechos otorgados en virtud de ella terminarán automáticamente si Usted infringe alguna condición establecida en ella. Sin embargo, los individuos o entidades que han recibido Obras Derivadas o Colectivas de Usted de conformidad con esta Licencia, no verán terminadas sus licencias, siempre que estos individuos o entidades sigan cumpliendo íntegramente las condiciones de estas licencias. Las Secciones 1, 2, 5, 6, 7, y 8 subsistirán a cualquier terminación de esta Licencia.

b.	Sujeta a las condiciones y términos anteriores, la licencia otorgada aquí es perpetua (durante el período de vigencia de los derechos de autor de la obra). No obstante lo anterior, el Licenciante se reserva el derecho a publicar y/o estrenar la Obra bajo condiciones de licencia diferentes o a dejar de distribuirla en los términos de esta Licencia en cualquier momento; en el entendido, sin embargo, que esa elección no servirá para revocar esta licencia o que deba ser otorgada , bajo los términos de esta licencia), y esta licencia continuará en pleno vigor y efecto a menos que sea terminada como se expresa atrás. La Licencia revocada continuará siendo plenamente vigente y efectiva si no se le da término en las condiciones indicadas anteriormente.

8. Varios.

a.	Cada vez que Usted distribuya o ponga a disposición pública la Obra o una Obra Colectiva, el Licenciante ofrecerá al destinatario una licencia en los mismos términos y condiciones que la licencia otorgada a Usted bajo esta Licencia.

b.	Si alguna disposición de esta Licencia resulta invalidada o no exigible, según la legislación vigente, esto no afectará ni la validez ni la aplicabilidad del resto de condiciones de esta Licencia y, sin acción adicional por parte de los sujetos de este acuerdo, aquélla se entenderá reformada lo mínimo necesario para hacer que dicha disposición sea válida y exigible.

c.	Ningún término o disposición de esta Licencia se estimará renunciada y ninguna violación de ella será consentida a menos que esa renuncia o consentimiento sea otorgado por escrito y firmado por la parte que renuncie o consienta.

d.	Esta Licencia refleja el acuerdo pleno entre las partes respecto a la Obra aquí licenciada. No hay arreglos, acuerdos o declaraciones respecto a la Obra que no estén especificados en este documento. El Licenciante no se verá limitado por ninguna disposición adicional que pueda surgir en alguna comunicación emanada de Usted. Esta Licencia no puede ser modificada sin el consentimiento mutuo por escrito del Licenciante y Usted.
0000-0002-9382-5962b18821a2a726f7505ba690b97bd8ba586000000-0002-4114-5965630fbc1ccf3770d19017048d54c4367b600 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