NS  Vol.5 No.7 A , July 2013
Heparin-binding proteins from boar seminal plasma affecting the release of prostaglandins and interleukin-6 by porcine endometrial and cervical cells and bovine endometrial cells
Abstract: The objectives of this study were to explore whether heparin-binding proteins, separated by fast protein liquid chromatography from boar seminal plasma influence the release of prostaglandins F2α, (PGF2α), E2 (PGE2) and interleukin-6 (IL-6) by porcine endometrial and cervical cells and even bovine endometrial cells. In Experiment I, we showed that release of PGF2α by endometrial epithelial, endometrial stromal and cervical stromal cells to the medium was inhibited (p < 0.05) to 9.0% - 60.6% after 24 h incubation with 125 μg of heparin-binding proteins. Tumor necrosis factor α (TNFα) stimulated release of IL-6 by endometrial and cervical stromal cells after 24 h incubation, but in the presence of heparin-binding proteins, this stimulation was attenuated. Release of PGF2α by cryopreserved (Experiment II) and primary (Experiment III) cervical stromal cells was significantly inhibited after 3 h incubation with 66 - 95.4 μg of heparin- binding proteins. A significant inhibition of PGE2 release by cryopreserved and primary cervical stromal cells was already achieved after incubation with 16.5 - 23.9 μg of heparin-binding proteins. The release of IL-6 by cryopreserved cells was stimulated after 3 h incubation with heparin- binding proteins in a dose dependent manner in contrast to the release of IL-6 by freshly isolated cervical stromal cells. We also found (Experiment IV) that porcine heparin-binding seminal plasma proteins inhibited release of PGF2α and stimulated release of IL-6 by bovine endometrial epithelial cells. In conclusion, a group of heparin-binding proteins separated by fast protein liquid chromatography from boar seminal plasma inhibit PGF2α, PGE2 and stimulate IL-6 release by porcine endometrial and cervical cells and even by bovine endometrial cells. Thus, these proteins have a similar effect as the entire seminal plasma.
Cite this paper: Madej, M. , Hansen, C. , Johannisson, A. and Madej, A. (2013) Heparin-binding proteins from boar seminal plasma affecting the release of prostaglandins and interleukin-6 by porcine endometrial and cervical cells and bovine endometrial cells. Natural Science, 5, 21-30. doi: 10.4236/ns.2013.57A004.

[1]   Madej, M., Norrby, M., Madsen, M.T., Johannisson, A., Hansen, C. and Madej, A. (2012) The effect of boar seminal plasma on the release of prostaglandins and inter leukin-6 by porcine endometrial and cervical cells and bovine endometrial cells. Reproduction in Domestic Animals, 47, 113-124. doi:10.1111/j.1439-0531.2011.01809.x

[2]   De Rensis, F., Saleri, R., Tummaruk, P., Techakumphu, M. and Kirkwood, R.N. (2011) Prostaglandin F2α and control of reproduction in female swine: A review. Theriogenology, 77, 1-11. doi:10.1016/j.theriogenology.2011.07.035

[3]   Ziecik, A.J., Waclawik, A., Kaczmarek, M.M., Blitek, A., Jalali, B.M. and Andronowska, A. (2011) Mechanisms for the establishment of pregnancy in the pig. Reproduction in Domestic Animals, 46, 31-41. doi:10.1007/s10059-010-0157-1

[4]   Basu, S. (2010) Bioactive eicosanoids: Role of prostaglandin F2α and F2-isoprostanes in inflammation and oxidative stress related pathology. Molecules and Cells, 30, 383-391. doi:10.1538/expanim.60.7

[5]   Murakami, M. (2011) Lipid mediators in life science. Experimental Animals, 60, 7-20.

[6]   Rozeboom, K.J., Troedsson, M.H., Molitor, T.W. and Crabo, B.G. (1999) The effect of spermatozoa and seminal plasma on leukocyte migration into the uterus of gilts. Journal of Animal Science, 77, 2201-2206.

[7]   Jiwakanon, J., Persson, E., Berg, M. and Dalin, A.M. (2011) Influence of seminal plasma, spermatozoa and semen extender on cytokine expression in the porcine endometrium after insemination. Animal Reproduction Science, 123, 210-220. doi:10.1016/j.anireprosci.2010.11.016

[8]   Rozeboom, K.J., Troedsson, M.H.T., Hodson, H.H., Shurson, G.C. and Crabo, B.G. (2000) The importance of seminal plasma on the fertility of subsequent artificial inseminations in swine. Journal of Animal Science, 78, 443-448.

[9]   Rozeboom, K.J., Troedsson, M.H., Rocha, G.R. and Crabo, B.G. (2001) The chemotactic properties of porcine seminal components toward neutrophils in vitro. Journal of Animal Science, 79, 996-1002.

[10]   Bischof, R.J., Lee, C.S., Brandon, M.R. and Meeusen, E. (1994) Inflammatory response in the pig uterus induced by seminal plasma. Journal of Reproductive Immunology, 26, 131-146. doi:10.1016/0165-0378(94)90036-1

[11]   O’Leary, S., Jasper, M.J., Warnes, G.M., Armstrong, D.T. and Robertson, S.A. (2004) Seminal plasma regulates endometrial cytokine expression, leukocyte recruitment and embryo development in the pig. Reproduction, 128, 237-247. doi:10.1530/rep.1.00160

[12]   Sanz, L., Calvete, J.J., Mann, K., Gabius, H.J. and Topferpetersen, E. (1993) Isolation and biochemical characterization of heparin-binding proteins from boar seminal plasma—a dual role for spermadhesins in fertilization. Molecular Reproduction and Development, 35, 37-43. doi:10.1002/mrd.1080350107

[13]   Jonakova, V., Kraus, M., Veselsky, L., Cechova, D., Bezouska, K. and Ticha, M. (1998) Spermadhesins of the AQN and AWN families, DQH sperm surface protein and HNK protein in the heparin-binding fraction of boar seminal plasma. Journal of Reproduction and Fertility, 114, 25-34.

[14]   Manaskova, P., Meszarosova, A., Liberda, J., Voburka, Z., Ticha, M. and Jonakova, V. (1999) Aggregated forms of heparin-binding and non-heparin-binding proteins of boar seminal plasma and their binding properties. Folia Biologica, 45, 193-201.

[15]   Caballero, I., Vazquez, J.M., Rodriguez-Martinez, H., Gil, M.A., Calvete, J.J., Sanz, L., Garcia, E.M., Roca, J. and Martinez, E.A. (2005) Influence of seminal plasma PSP-I/PSP-II spermadhesin on pig gamete interaction. Zygote, 13, 11-16. doi:10.1017/S0967199405003072

[16]   Caballero, I., Vazquez, J.M., García, E.M., Parrilla, I., Roca, J., Calvete, J.J., Sanz, L. and Martínez, E.A. (2008) Major proteins of boar seminal plasma as a tool for biotechnological preservation of spermatozoa. Theriogenology, 70, 1352-1355. doi:10.1016/j.theriogenology.2008.07.013

[17]   Rodriguez-Martinez, H., Saravia, F., Wallgren, M., Mar tinez, E.A., Sanz, L., Roca, J., Vazquez, J.M. and Calvete, J.J. (2010) Spermadhesin PSP-I/PSP-II heterodimer induces migration of polymorphonuclear neutrophils into the uterine cavity of the sow. Journal of Reproductive Immunology, 84, 57-65. doi:10.1016/j.jri.2009.10.007

[18]   Rodríguez-Martínez, H., Kvist, U., Ernerudh, J., Sanz, L. and Calvete, J.J. (2011) Seminal Plasma Proteins: What Role Do They Play? American Journal of Reproductive Immunology, 66, 11-22. doi:10.1111/j.1600-0897.2011.01033.x

[19]   Novak, S., Ruiz-Sanchez, A., Dixon, W. T., Foxcroft, G.R. and Dyck, M.K. (2010) Seminal plasma proteins as po tential markers of relative fertility in boars. Journal of Andrology, 31, 188-200. doi:10.2164/jandrol.109.007583

[20]   Dyck, M.K., Foxcroft, G.R., Novak, S., Ruiz-Sanchez, A., Patterson, J. and Dixon, W.T. (2011) Biological markers of boar fertility. Reproduction in Domestic Animals, 46, 55-58. doi:10.1111/j.1439-0531.2011.01837.x

[21]   Madsen, M.T., Larsen, M., Mathiasen, J., Kindahl, H., Einarsson, S. and Madej, A. (2002) Plasma levels of oxytocin and PGF2α metabolite during AI and mating in multiparous sows. Reproduction in Domestic Animals, 37, 242.

[22]   Madej, A., Lang, A., Brandt, Y., Kindahl, H., Madsen, M. T. and Einarsson, S. (2005) Factors regulating ovarian function in pigs. Domestic Animal Endocrinology, 29, 347-361. doi:10.1016/j.domaniend.2005.02.030

[23]   Norrby, M., Madsen, M.T., Alexandersen, C.B., Kindahl, H. and Madej, A. (2007) Plasma concentrations of cortisol and PGF2α metabolite in Danish sows during mating, and intrauterine and conventional insemination. Acta Veterinaria Scandinavica, 49, 36. doi:10.1186/1751-0147-49-36

[24]   Varilova, T., Semenkova, H., Horak, P., Madera, M., Pacakova, V., Ticha, M. and Stulik, K. (2006) Affinity liquid chromatography and capillary electrophoresis of seminal plasma proteins. Journal of Separation Science, 29, 1110-1115. doi:10.1002/jssc.200500405

[25]   Zhang, Z., Paria, B.C. and Davis, D.L. (1991) Pig endometrial cells in primary culture: Morphology, secretion of prostaglandins and proteins, and effects of pregnancy. Journal of Animal Science, 69, 3005-3015.

[26]   Uzumcu, M., Braileanu, G.T., Carnahan, K.G., Ludwig, T.E. and Mirando, M.A. (1998) Oxytocin-stimulated phosphoinositide hydrolysis and prostaglandin f secretion by luminal epithelial, glandular epithelial, and stromal cells from pig endometrium. I. Response of cyclic pigs on day 16 postestrus. Biology of Reproduction, 59, 1259-1265. doi:10.1095/biolreprod59.5.1259

[27]   Guseva, N.V., Knight, S.T., Whittimore, J.D. and Wyrick, P.B. (2003) Primary cultures of female swine genital epithelial cells in vitro: A new approach for the study of hormonal modulation of chlamydia infection. Infection and Immunity, 71, 4700-4710. doi:10.1128/IAI.71.8.4700-4710.2003

[28]   Blitek, A. and Ziecik, A.J. (2004) Prostaglandins F-2 alpha and E-2 secretion by porcine epithelial and stromal endometrial cells on different days of the oestrous cycle. Reproduction in Domestic Animals, 39, 340-346. doi:10.1111/j.1439-0531.2004.00523.x

[29]   Dernfalk, J., Persson Waller, K. and Johannisson, A. (2007) The xMAP (TM) technique can be used for detection of the inflammatory cytokines IL-1 beta, IL-6 and TNF-alpha bovine samples. Veterinary Immunology and Immunopathology, 118, 40-49. doi:10.1016/j.vetimm.2007.04.004

[30]   Calvete, J. J., Raida, M., Gentzel, M., Urbanke, C., Sanz, L. and TÖpfer-Petersen, E. (1997) Isolation and characterization of heparin and phosphorylcholine-binding proteins of boar and stallion seminal plasma. Primary structure of porcine pB1. FEBS Letters, 407, 201-206. doi:10.1016/S0014-5793(97)00344-X

[31]   Strzezek, J. (2002) Secretory activity of boar seminal vesicle glands. Reproductive Biology, 2, 243-266.

[32]   Calvete, J.J., Mann, K., Schafer, W., Raida, M., Sanz, L. and Topferpetersen, E. (1995) Boar spermadhesin PSP-II: Location of posttranslational modifications, heterodimer formation with PSP-I glycoforms and effect of dimerization on the ligand-binding capabilities of the subunits. FEBS Letters, 365, 179-182. doi:10.1016/0014-5793(95)00452-F

[33]   Manaskova, P., Liberda, J., Ticha, M. and Jonakova, V. (2002) Isolation of non-heparin-binding and heparin binding proteins of boar prostate. Journal of Chromato graphy B—Analytical Technologies in the Biomedical and Life Sciences, 770, 137-143. doi:10.1016/S0378-4347(01)00480-7

[34]   Basu, S. (2007) Novel cyclooxygenase-catalyzed bioactive prostaglandin F2α from physiology to new principles in inflammation. Medicinal Research Reviews, 27, 435-468. doi:10.1002/med.20098

[35]   Serhan, C.N., Chiang, N. and Van Dyke, T.E. (2008) Re solving inflammation: Dual anti-inflammatory and pro resolution lipid mediators. Nature Reviews Immunology, 8, 349-361. doi:10.1038/nri2294

[36]   Taylor, U., Zerbe, H., Seyfert, H.M., Rath, D., Baulain, U., Langner, K.F.A. and Schuberth, H.J. (2009) Porcine spermatozoa inhibit post-breeding cytokine induction in uterine epithelial cells in vivo. Animal Reproduction Science, 115, 279-289. doi:10.1016/j.anireprosci.2008.11.019

[37]   Aloe, S., Weber, F., Behr, B., Sauter-Louis, C. and Zerbe, H. (2012) Modulatory effects of bovine seminal plasma on uterine inflammatory processes. Reproduction in Domestic Animals, 47, 12-19. doi:10.1111/j.1439-0531.2011.01792.x

[38]   Hansen, C., Madej, M. and Madej, A. (2013) Profile of seminal plasma proteins in relation to boars fertility—A pilot study. Program and Abstract Book, 9th International Conference on Pig Reproduction in Olsztyn, Poland, 9-12 June 2013, 149.

[39]   Kaczmarek, M.M., Krawczynski, K. and Filant, J. (2013) Seminal plasma affects prostaglandin synthesis and an giogenesis in the porcine uterus. Biology of Reproduction, 88, 72.

[40]   Li, J.C., Yamaguchi, S. and Funahashi, H. (2012) Boar seminal plasma or hen’s egg yolk decrease the in-vitro chemotactic and phagocytotic activities of neutrophils when co-incubated with boar or bull sperm. Theriogenology, 77, 73-80. doi:10.1016/j.theriogenology.2011.07.018

[41]   Caballero, I., Parrilla, I., Alminana, C., del Olmo, D., Ro ca, J., Martínez, E.A. and Vázquez, J.M. (2012) Seminal plasma proteins as modulators of the sperm function and their application in sperm biotechnologies. Reproduction in Domestic Animals, 47, 12-21. doi:10.1111/j.1439-0531.2012.02028.x

[42]   Kimura, A. and Kishimoto, T. (2010) IL-6: Regulator of Treg/Th17 balance. European Journal of Immunology, 40, 1830-1835. doi:10.1002/eji.201040391

[43]   Gutsche, S., von Wolff, M., Strowitzki, T. and Thaler, C.J. (2003) Seminal plasma induces mrna expression of IL-10, IL-6 and LIF in endometrial epithelial cells in vitro. Molecular Human Reproduction, 9, 785-791. doi:10.1093/molehr/gag095

[44]   von Wolff, M., Nowak, O., Pinheiro, R.M. and Strowitzki, T. (2007) Seminal plasma—Immunomodulatory potential in men with normal and abnormal sperm count. European Journal of Obstetrics Gynecology and Reproductive Bio logy, 134, 73-78. doi:10.1016/j.ejogrb.2007.01.009

[45]   Østrup, E., Bauersachs, S., Blum, H., Wolf, E. and Hyttel, P. (2010) Differential endometrial gene expression in pre gnant and nonpregnant sows. Biology of Reproduction, 83, 277-285. doi:10.1095/biolreprod.109.082321

[46]   Bersinger, N., Günthert, A., McKinnon, B., Johann, S. and Mueller, M. (2011) Dose-response effect of inter leukin (IL)-1β, tumour necrosis factor (TNF)-α, and inter feron-γ on the in vitro production of epithelial neutrophil activating peptide-78 (ENA-78), IL-8, and IL-6 by human endometrial stromal cells. Archives of Gynecology and Obstetrics, 283, 1291-1296. doi:10.1007/s00404-010-1520-3

[47]   Lee, H.Y., Acosta, T.J., Tanikawa, M., Sakumoto, R., Komiyama, J., Tasaki, Y., Piskula, M., Skarzynski, D.J., Tetsuka, M. and Okuda, K. (2007) The role of glucocor ticoid in the regulation of prostaglandin biosynthesis in non-pregnant bovine endometrium. Journal of Endocrinology, 193, 127-135. doi:10.1677/joe.1.06975

[48]   Einspanier, R., Krause, I., Calvete, J.J., TÖfper-Petersen, E., Klostermeyer, H. and Karg, H. (1994) Bovine seminal plasma ASFP: Localization of disulfide bridges and detection of three different isoelectric forms. FEBS Letters, 344, 61-64. doi:10.1016/0014-5793(94)00362-9

[49]   Reinert, M., Calvete, J.J., Sanz, L., Mann, K. and TÖpfer Petersen, E. (1996) Primary structure of stallion seminal plasma protein HSP-7, a zona-pellucida-binding protein of the spermadhesin family. European Journal of Biochemistry, 242, 636-640. doi:10.1111/j.1432-1033.1996.0636r.x

[50]   Lusignan, M.F., Bergeron, A., Crete, M.H., Lazure, C. and Manjunath, P. (2007) Induction of epididymal boar sperm capacitation by pB1 and BSP-A1/-A2 proteins, members of the BSP protein family. Biology of Repro duction, 76, 424-432. doi:10.1095/biolreprod.106.055624