Skip to main content
Log in

Immunohistochemical localization of beta defensins in the endometrium of rat uterus during the postpartum involution period

  • Original Article
  • Published:
Veterinary Research Communications Aims and scope Submit manuscript

Abstract

β-Defensins are small cationic molecules that have antimicrobial actions against bacteria, fungi and viruses and contribute to mucosal immune responses at epithelial sites. The female reproductive tract is an important site of defensin production. This study was conducted to determine the possible changes in proportions and localization of β-defensin 1-4 in the rat uterus at the 1st, 3th, 5th, 10th and 15th days of postpartum and at the period of diestrus using immunohistochemical techniques. In the present study, it was determined that β-defensin 1-4 were generally found in all structural components of the endometrium (luminal and glandular epithelium, stromal cells and blood vessels) in both the nucleus and the cytoplasm of cells during the involution period and diestrus. Suprisingly, immunoreaction of β-defensin 2 was also observed in the lateral membrane of the luminal and glandular epithelial cells on the 10th day of involution and immunostaining of β-defensin 4 was also localized in the apical membrane of the luminal and glandular epithelial cells. The current study demonstrated β-defensin 1-4 immunoreactivities in the endothelium of blood vessels were stronger throughout the involution period. Although β-defensins 2 and 3 were localized in both the nuclei and the cytoplasm of endothelial cells, β-defensins 1 and 4 were present in only cytoplasm. These results show that the most component of rat endometrium expresses human β-defensin 1-4 in a involution-dependent manner. Therefore it may be asserted that these molecules constitute a organised protection to prevent uterus from probable infections during the involution process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Agerberth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L, Kiessling R, Jornvall H, Wigzell H, Gudmundsson GH (2000) The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood 96:3086–3093

    PubMed  CAS  Google Scholar 

  • Ashkar AA, Di Santo JP, Croy BA (2000) Interferon gamma contributes to initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal murine pregnancy. J Exp Med 192:259–270

    Article  PubMed  CAS  Google Scholar 

  • Bals R, Wang X, Zasloff M, Wilson JM (1998a) The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway luminal. Proc Natl Acad Sci USA 95:9541–9546

    Article  PubMed  CAS  Google Scholar 

  • Bals R, Wang X, Wu Z, Freeman T, Bafna V, Zasloff M, Wilson JM (1998b) Human β-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. J Clin Invest 102:874–880

    Article  PubMed  CAS  Google Scholar 

  • Bevins CL (2006) Paneth cell defensins: key effector molecules of innate immunity. Biochem Soc Trans 34:263–266

    Article  PubMed  CAS  Google Scholar 

  • Bhat S, Bick RJ, Poindexter BJ, Buja M, Milner SM (2006) Perinuclear and nuclear localization of Human Beta Defensin 1 and 2. The Wound Healing Society, 16th Annual Meeting. Scottsdale, AZ. April. Wound Repair Regen 14:A54

    Google Scholar 

  • Bhat S, Bick R, Poindexter BJ, Lawyer C, Milner SM (2007) Nuclear localization of human beta defensin 1 and 2. Proc Amer Burn Assoc, 39th Annual Meeting. San Diego, CA. March. J Burn Care Res 28(2 Suppl):S115

    Google Scholar 

  • Bick RJ, Poindexter BJ, Buja LM, Lawyer CH, Milner SM, Bhat S (2007) Nuclear localization of HBD1 in human keratinocytes. J Burns Wounds 7:25–32

    Google Scholar 

  • Butmarc J, Yufit T, Carson P, Falanga V (2004) Human beta-defensin-2 expression is increased in chronic wounds. Wound Repair Regen 12:439–443

    Article  PubMed  Google Scholar 

  • Dale BA, Krisanaprakornkit S (2001) Defensin antimicrobial peptides in the oral cavity. J Oral Pathol Med 30:321–327

    Article  PubMed  CAS  Google Scholar 

  • Das S, Vince GS, Lewis-Jones I, Bates MD, Gazvani R (2007) The expression of human alpha and beta defensin in the endometrium and their effects on implantation. J Assist Reprod Genet 24:533–539

    Article  PubMed  CAS  Google Scholar 

  • De Falco G, Bagella L, Claudio PP, De Luca A, Fu Y, Calabretta B, Sala A, Giordano A (2000) Physical interaction between CDK9 and B-Myb results in suppression of B-Myb gene autoregulation. Oncogene 19:373–379

    Article  PubMed  Google Scholar 

  • Dhaliwal GS, Murray RD, Woldehiwet Z (2001) Some aspects of immunology of the bovine uterus related to treatments for endometritis. Anim Reprod Sci 67:135–152

    Article  PubMed  CAS  Google Scholar 

  • Dorschner RA, Pestonjamasp VK, Tamakuwala S, Ohtake T, Rudisill J, Nizet V, Agerberth B, Gudmundsson GH, Gallo RL (2001) Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A Streptococcus. J Investig Dermatol 117:91–97

    Article  PubMed  CAS  Google Scholar 

  • Dubuc J, Duffield TF, Leslie KE, Walton JS, LeBlanc SJ (2010) Risk factors for postpartum uterine diseases in dairy cows. J Dairy Sci 93:5764–5771

    Article  PubMed  CAS  Google Scholar 

  • Fellermann K, Stange EF (2001) Defensins innate immunity at the epithelial frontier. Eur J Gastroenterol Hepatol 13:771–776

    Article  PubMed  CAS  Google Scholar 

  • Feng Y, Pan X, Huang N, Feng Y, Wu Q, Wang B (2003) The human beta-defensins expression in female genital tract and pregnancy-related tissues. Sichuan Da Xue Xue Bao Yi Xue Ban 34:217–219

    PubMed  CAS  Google Scholar 

  • Fleming DC, King AE, Critchley HOD, Williams ARW, Kelly RW (2003) Hormonal contraception can suppress natural antimicrobial gene transcription in human endometrium. Fertil Steril 76:856–863

    Article  Google Scholar 

  • Ganz T (2004) Defensins: antimicrobial peptides of vertebrates. C R Biol 327:539–549

    Article  PubMed  CAS  Google Scholar 

  • Ganz T, Selsted ME, Lehrer RI (1990) Defensins. Eur J Hematol 44:1–8

    Article  CAS  Google Scholar 

  • Hajurka J, Macak V, Hura V (2005) Influence of health status of reproductive organs on uterine involution in dairy cows. Bull Vet Inst Pulawy 49:53–58

    Google Scholar 

  • Harder J, Bartels J, Christophers E, Schroder JM (2001) Isolation and characterization of human beta-defensin-3, a novel human inducible peptide antibiotic. J Biol Chem 276:5707–5713

    Article  PubMed  CAS  Google Scholar 

  • Henell F, Ericsson JLE, Glaumann H (1982) An electron microscopic study of the post-partum involution of the rat uterus with a note on apparent crinophagy of collagen. Virchows Archiv B Cell Pathol Zell-Pathol 41:271–287

    Article  Google Scholar 

  • Huh WK, Oono T, Shirafuji Y, Akiyama H, Arata J, Sakaguchi M, Huh NH, Iwatsuki K (2002) Dynamic alteration of human beta-defensin 2 localization from cytoplasm to intercellular space in psoriatic skin. J Mol Med (Berl) 80:678–684

    Article  CAS  Google Scholar 

  • Huttner KM, Bevins CL (1999) Antimicrobial peptides as mediators of epithelial host defense. Pediatr Res 45:785–794

    Article  PubMed  CAS  Google Scholar 

  • Jiao Y, Sun Z, Lee T, Fusco FR, Kimble TD, Meade CA, Cuthberston S, Reiner A (1999) A simple and sensitive antigen retrieval method for free-floating and slide-mounted tissue sections. J Neurosci Methods 93:149–162

    Article  PubMed  CAS  Google Scholar 

  • Kaiser V, Diamond G (2000) Expression of mammalian defensin genes. J Leukoc Biol 68:779–784

    PubMed  CAS  Google Scholar 

  • King AE, Critchley HO, Kelly RW (2003a) Innate immune defences in the human endometrium. Reprod Biol Endocrinol 1:116

    Article  PubMed  Google Scholar 

  • King AE, Fleming DC, Critchley HO, Kelly RW (2003b) Differential expression of the natural antimicrobials, beta-defensins 3 and 4 in human endometrium. J Reprod Immunol 59:1–16

    Article  PubMed  CAS  Google Scholar 

  • King AE, Paltoo A, Kelly RW, Sallenave JM, Bocking AD, Challis CR (2007) Expression of natural antimicrobials by human placenta and fetal membranes. Placenta 28:161–169

    Article  PubMed  CAS  Google Scholar 

  • Klagsbrun M, D’Amore PA (1991) Regulators of angiogenesis. Annu Rev Physiol 53:217–239

    Article  PubMed  CAS  Google Scholar 

  • Koczulla R, von Degenfeld G, Kupatt C, Krötz F, Zahler S, Gloe T, Issbrücker K, Unterberger P, Zaiou M, Lebherz C, Karl A, Raake P, Pfosser A, Boekstegers P, Welsch U, Hiemstra PS, Vogelmeier C, Gallo RL, Clauss M, Bals R (2003) An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J Clin Invest 111:1665–1672

    Google Scholar 

  • Lehrer RI (2007) Multispecific myeloid defensins. Curr Opin Hematol 14:16–21

    Article  PubMed  CAS  Google Scholar 

  • Li WW, Talcott KE, Zhai AW, Kruger EA, Li VW (2005) The role of therapeutic angiogenesis in tissue repair and regeneration. Adv Skin Wound Care 18:491–500

    Article  PubMed  Google Scholar 

  • Li J, Raghunath M, Tan D, Lareu RR, Chen Z, Beuerman RW (2006) Defensins HNP1 and HBD2 stimulation of wound-associated responses in human conjunctival fibroblasts. Invest Ophthalmol Vis Sci 47:3811–3819

    Article  PubMed  Google Scholar 

  • Luenser K, Ludwig A (2005) Variability and evolution of bovine β-defensin genes. Genes Immun 6:115–122

    Article  PubMed  CAS  Google Scholar 

  • Manase K, Endo T, Chida M, Nagasawa K, Honnma H, Yamazaki K, Kitajima Y, Goto T, Kanaya M, Hayashi T, Mitaka T, Saito T (2006) Coordinated elevation of membrane type 1-matrix metalloproteinase and matrix metalloproteinase-2 expression in rat uterus during postpartum involution. Reprod Biol Endocrinol 4:32. doi:10.1186/1477-7827-4-32

    Article  PubMed  Google Scholar 

  • McCray PB Jr, Bentley L (1997) Human airway epithelia express a beta-defensin. Am J Respir Cell Mol Biol 16:343–349

    PubMed  CAS  Google Scholar 

  • McNamara NA, Van R, Tuchin OS, Fleiszig SM (1999) Ocular luminal epithelia express mRNA for human beta defensin-2. Exp Eye Res 69:483–490

    Article  PubMed  CAS  Google Scholar 

  • Niyonsaba F, Ushio H, Nakano N, Ng W, Sayama K, Hashimoto K, Nagaoka I, Okumura K, Ogawa H (2007) Antimicrobial peptides human β-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokines. J Invest Dermatol 127:594–604

    Article  PubMed  CAS  Google Scholar 

  • Ohara T, Morishita T, Suzuki H, Masaoka T, Nagata H, Hibi T (2004) Pathophysiological role of human beta-defensins 2 in gastric mucosa. Int J Mol Med 14:1023–1027

    PubMed  CAS  Google Scholar 

  • Pantelis A, Wenghoefer M, Haas S, Merkelbach-Bruse S, Pantelis D, Jepsen S, Bootz F, Winter J (2009) Down regulation and nuclear localization of humanβ-defensin-1 in pleomorphic adenomas of salivary glands. Oral Oncol 45:526–530

    Article  PubMed  CAS  Google Scholar 

  • Poindexter BJ (2005) Immunofluorescence deconvolution microscopy and image reconstruction of human defensins in normal and burned skin. J Burns Wounds 4:101–111

    Google Scholar 

  • Quayle AJ (2002) The innate and early immune response to pathogen challenge in the female genital tract and the pivotal role of epithelial cells. J Reprod Immunol 57:61–79

    Article  PubMed  CAS  Google Scholar 

  • Quayle AJ, Porter EM, Nussbaum AA, Wang YM, Brabec C, Yip KP, Mok SC (1998) Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract. Am J Pathol 152:1247–1258

    PubMed  CAS  Google Scholar 

  • Reynolds LP (1986) Utero-ovarian interactions during early pregnancy: role of conceptus-induced vasodilation. J Anim Sci 2:47–61

    Google Scholar 

  • Reynolds LP, Killilea SD, Redmer DA (1992) Angiogenesis in the female reproductive system. FASEB J 6:886–892

    PubMed  CAS  Google Scholar 

  • Salamonsen LA (2003) Tissue injury and repair in the female human reproductive tract. Reproduction 125:301–311

    Article  PubMed  CAS  Google Scholar 

  • Sheldon IM (2004) The postpartum uterus. Vet Clin N Am Food Anim Pract 20:569–591

    Article  Google Scholar 

  • Sheldon IM, Dobson H (2004) Postpartum uterine health in cattle. Anim Reprod Sci 82–83:295–306

    Article  PubMed  Google Scholar 

  • Singh J, Murray RD, Mshelia G, Woldehiwet Z (2008) The immune status of the bovine uterus during the peripartum period. Vet J 175:301–309

    Article  PubMed  CAS  Google Scholar 

  • Soboll G, Shen L, Wira CR (2006a) Expression of Toll-like receptors (TLR) and responsiveness to TLR agonists by polarized mouse uterine epithelial cells in culture. Biol Reprod 75:131–139

    Article  PubMed  CAS  Google Scholar 

  • Soboll G, Schaefer TM, Wira CR (2006b) Effect of Toll-like receptor (TLR) agonists on TLR and microbicide expression in uterine and vaginal tissues of the mouse. Am J Reprod Immunol 55:434–446

    Article  PubMed  CAS  Google Scholar 

  • Svinarich DM, Wolf NA, Gomez R, Gonik B, Romero R (1997) Detection of human defensin 5 in reproductive tissues. Am J Obstet Gynecol 176:470–475

    Article  PubMed  CAS  Google Scholar 

  • Valore EV, Park CH, Quayle AJ, Wiles KR, McCray PB Jr, Ganz T (1998) Human β-defensin-1: an antimicrobial peptide of urogenital tissues. J Clin Invest 101:1633–1642

    Article  PubMed  CAS  Google Scholar 

  • Wenghoefer M, Pantelis A, Dommisch H, Götz W, Reich R, Bergé S, Martini M, Allam JP, Jepsen S, Merkelbach-Bruse S, Fischer HP, Novak N, Winter J (2008) Nuclear HBD1 accumulation in malignant salivary gland tumours. BMC Cancer 8:290–297

    Article  PubMed  CAS  Google Scholar 

  • Wira CR, Grant-Tschudy KS, Crane-Godreau MA (2005) Epithelial cells in the female reproductive tract: a central role as sentinels of immune protection. Am J Reprod Immunol 53:65–76

    Article  PubMed  CAS  Google Scholar 

  • Yanagi S, Ashitani J, Ishimoto H, Date Y, Mukae H, Chino N, Nakazato M (2005) Isolation of human β-defensin-4 in lung tissue and its increase in lower respiratory tract infection. Respir Res 4(6):110

    Google Scholar 

  • Yongming S, Amar AP, Guolong Z, Chris R, Frank B (2006) Bioinformatic and expression analysis of novel porcine β-defensins. Mamm Genome 17:332–339

    Article  Google Scholar 

  • Zanetti M (2004) Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol 75:39–48

    Article  PubMed  Google Scholar 

  • Zasloff M (2002) Antimicrobial peptides of multicellular organisms. Nature 415:389–395

    Article  PubMed  CAS  Google Scholar 

  • Zhao C, Wang I, Lehrer RI (1996) Widespread expression of beta-defensin HBD1 in human secretory glands and epithelial cells. FEBS Lett 396:319–322

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was summarized from Emel ALAN’s doctorate thesis and it was financially supported by Scientific Research Council of Erciyes University (Project No: TSD-08-624).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Narin Liman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alan, E., Liman, N. Immunohistochemical localization of beta defensins in the endometrium of rat uterus during the postpartum involution period. Vet Res Commun 36, 173–185 (2012). https://doi.org/10.1007/s11259-012-9529-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11259-012-9529-7

Keywords

Navigation