Skip to main content

Expression of prostaglandin (PG) D synthase lipocalin and hematopoietic type and PG D receptor during restart of spermatogenesis following downregulation using a slow release GnRH agonist implant in the dog

Abstract

Prostaglandin D and the associated prostaglandin D synthases (PGDS) and receptor (DP) are considered to be involved in spermatogenesis. However, the interplay of the PGDS-DP system in male reproduction is far from being understood. The expression of PGDS lipocalin (L) and hematopoietic (H) type and DP was studied in the GnRH agonist–downregulated canine testis (week, w 0) and during recrudescence of spermatogenesis after implant removal (w 3, 6, 9, 12). H-PGDS, L-PGDS and DP were present in the adult (CG), juvenile (JG) and downregulated canine testis at the mRNA level. PGDS immunohistochemistry revealed positive staining in the cytoplasm of Leydig cells (LCs) of all samples i.e., no difference between groups. mRNA expression (ratio) of L-, H-PGDS and DP did not differ between groups w 0–12 and CG. In contrast, significant differences were found for L-PGDS (p = 0.0388), H-PGDS (p < 0.001) and DP (p < 0.001) for the groups at downregulation (w0, suprelorin group, SG, profact group, PRG) compared with the control groups (JG, CG). L-PGDS expression was lowest in JG, whereas H-PGDS was significantly lower in CG compared with JG and at downregulation (p < 0.001 to p < 0.01). The highest ratio for H-PGDS and DP was observed in the dogs treated with buserelin acetate (PRG). Our data show that the PGDS-DP system is expressed in juvenile and adult canine testes and that downregulation of the testicular endocrine and germinative function significantly affects H-PGDS, L-PGDS and DP mRNA expression indicating a role in the regulation of spermatogenesis.

This is a preview of subscription content, access via your institution.

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

References

  1. Baker P, O'Shaughnessy P (2001) Expression of prostaglandin D synthetase during development in the mouse testis. Reproduction 122(4):553–559. https://doi.org/10.1530/rep.0.1220553

    CAS  Article  PubMed  Google Scholar 

  2. Chaudhary LR, Stocco DM (1990) An in vitro cell model system to study the action of retinoids on Leydig cell steroidogenesis. Biochem Int 21(6):1033–1042

    CAS  PubMed  Google Scholar 

  3. Chaudhary LR, Hutson JC, Stocco DM (1989) Effect of retinol and retinoic acid on testosterone production by rat Leydig cells in primary culture. Biochem Biophys Res Commun 158(2):400–406

    CAS  Article  Google Scholar 

  4. Chen D-Y, Zhu M-Y, Cui Y-D, Huang T-H (2007) Relationship between contents of lipocalin-type prostaglandin D synthase on the surface of infertility sperm and in seminal plasma. Biochemistry (Mosc.) 72(2):215–218

    CAS  Article  Google Scholar 

  5. Fouchécourt S, Dacheux F, Dacheux JL (1999) Glutathione-independent prostaglandin D2 synthase in ram and stallion epididymal fluids. Origin and regulation. Biol Reprod 60(3):558–566

    Article  Google Scholar 

  6. Frungieri MB, Calandra RS, Mayerhofer A, Matzkin ME (2015) Cyclooxygenase and prostaglandins in somatic cell populations of the testis. Reproduction 149(4):R169–R180. https://doi.org/10.1530/REP-14-0392

    CAS  Article  PubMed  Google Scholar 

  7. Fuchs A-R, Chantharaksri U (1981) Prostaglandin F2α regulation of LH-stimulated testosterone production in rat testis1. Biol Reprod 25(3):492–501. https://doi.org/10.1095/biolreprod25.3.492

    CAS  Article  PubMed  Google Scholar 

  8. Gentil M, Hoffmann B, Spang A, Failing K, Goericke-Pesch S (2012) Restart of steroidogenesis in dogs during recrudescence of testicular function following downregulation with a GnRH-agonist implant. Cell Tissue Res 350(3):513–523. https://doi.org/10.1007/s00441-012-1506-5

    CAS  Article  PubMed  Google Scholar 

  9. Gerena RL, Irikura D, Urade Y, Eguchi N, Chapman DA, Killian GJ (1998) Identification of a fertility-associated protein in bull seminal plasma as lipocalin-type prostaglandin D synthase. Biol Reprod 58(3):826–833

    CAS  Article  Google Scholar 

  10. Gerena RL, Eguchi N, Urade Y, Killian GJ (2000a) Stage and region-specific localization of lipocalin-type prostaglandin D synthase in the adult murine testis and epididymis. J Androl 21(6):848–854

    CAS  PubMed  Google Scholar 

  11. Gerena RL, Irikura D, Eguchi N, Urade Y, Killian GJ (2000b) Immunocytochemical localization of lipocalin-type prostaglandin D synthase in the bull testis and epididymis and on ejaculated sperm1. Biol Reprod 62(3):547–556. https://doi.org/10.1095/biolreprod62.3.547

    CAS  Article  PubMed  Google Scholar 

  12. Goericke-Pesch S, Spang A, Schulz M, Ozalp G, Bergmann M, Ludwig C, Hoffmann B (2009) Recrudescence of spermatogenesis in the dog following downregulation using a slow release GnRH agonist implant. Reprod Dom Anim 44(Suppl 2):302–308. https://doi.org/10.1111/j.1439-0531.2009.01378.x

    Article  Google Scholar 

  13. Goericke-Pesch S, Gentil M, Spang A, Kowalewski MP, Failing K, Hoffmann B (2013) Status of the down-regulated canine testis using two different GNRH agonist implants in comparison with the juvenile testis. Reproduction 146(6):517–526. https://doi.org/10.1530/REP-13-0195

    CAS  Article  PubMed  Google Scholar 

  14. Griswold MD (2016) Spermatogenesis: the commitment to meiosis. Physiol Rev 96(1):1–17. https://doi.org/10.1152/physrev.00013.2015

    CAS  Article  PubMed  Google Scholar 

  15. Hoffmann B, Büsges F, Baumgärtner W (2004) Immunohistochemical detection of CD4-, CD8- and MHC II-expressing immune cells and endoglin in the canine corpus luteum at different stages of dioestrus. Reprod Dom Anim 39(6):391–395. https://doi.org/10.1111/j.1439-0531.2004.00520.x

    CAS  Article  Google Scholar 

  16. Jin G, Guo L, Zhang Y, Xue Y, Zhang X, Wang X, Wang D, Li B, Zhao P, Xu F, Cheng J (2017) Expression and localization of lipocalin-type-prostaglandin D synthase in the goat testis, epididymis and sperm. Small Rum Res 154:1–4. https://doi.org/10.1016/j.smallrumres.2017.06.020

    Article  Google Scholar 

  17. Kanaoka Y, Urade Y (2003) Hematopoietic prostaglandin D synthase. Prostaglandins Leukot Essent Fat Acids 69(2–3):163–167

    CAS  Article  Google Scholar 

  18. Kanaoka Y, Ago H, Inagaki E, Nanayama T, Miyano M, Kikuno R, Fujii Y, Eguchi N, Toh H, Urade Y, Hayaishi O (1997) Cloning and crystal structure of hematopoietic prostaglandin D synthase. Cell 90(6):1085–1095

    CAS  Article  Google Scholar 

  19. Kanaoka Y, Fujimori K, Kikuno R, Sakaguchi Y, Urade Y, Hayaishi O (2000) Structure and chromosomal localization of human and mouse genes for hematopoietic prostaglandin D synthase. Conservation of the ancestral genomic structure of sigma-class glutathione S-transferase. Eur J Biochem 267(11):3315–3322

    CAS  Article  Google Scholar 

  20. Körber H, Goericke-Pesch S (2018) Expression of PTGS2, PGFS and PTGFR during downregulation and restart of spermatogenesis following GnRH agonist treatment in the dog. Cell Tissue Res. https://doi.org/10.1007/s00441-018-2915-x

    Article  Google Scholar 

  21. Matsuoka T, Hirata M, Tanaka H, Takahashi Y, Murata T, Kabashima K, Sugimoto Y, Kobayashi T, Ushikubi F, Aze Y, Eguchi N, Urade Y, Yoshida N, Kimura K, Mizoguchi A, Honda Y, Nagai H, Narumiya S (2000) Prostaglandin D2 as a mediator of allergic asthma. Science (New York, NY) 287(5460):2013–2017

    CAS  Article  Google Scholar 

  22. Moniot B, Declosmenil F, Barrionuevo F, Scherer G, Aritake K, Malki S, Marzi L, Cohen-Solal A, Georg I, Klattig J, Englert C, Kim Y, Capel B, Eguchi N, Urade Y, Boizet-Bonhoure B, Poulat F (2009) The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation. Development 136(11):1813–1821. https://doi.org/10.1242/dev.032631

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Moniot B, Farhat A, Aritake K, Declosmenil F, Nef S, Eguchi N, Urade Y, Poulat F, Boizet-Bonhoure B (2011) Hematopoietic prostaglandin D synthase (H-Pgds) is expressed in the early embryonic gonad and participates to the initial nuclear translocation of the SOX9 protein. Dev dyn 240(10):2335–2343. https://doi.org/10.1002/dvdy.22726

    CAS  Article  PubMed  Google Scholar 

  24. Moniot B, Ujjan S, Champagne J, Hirai H, Aritake K, Nagata K, Dubois E, Nidelet S, Nakamura M, Urade Y, Poulat F, Boizet-Bonhoure B (2014) Prostaglandin D2 acts through the Dp2 receptor to influence male germ cell differentiation in the foetal mouse testis. Development 141(18):3561–3571. https://doi.org/10.1242/dev.103408

    CAS  Article  PubMed  Google Scholar 

  25. Nagata N, Urade Y (2012) Sleep-wake regulation by prostaglandin D2 and adenosine. Brain Nerve 64(6):621–628

    CAS  PubMed  Google Scholar 

  26. O'Shaughnessy PJ, Willerton L, Baker PJ (2002) Changes in Leydig cell gene expression during development in the mouse. Biol Reprod 66(4):966–975

    CAS  Article  Google Scholar 

  27. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29(9):e45

    CAS  Article  Google Scholar 

  28. Rossitto M, Ujjan S, Poulat F, Boizet-Bonhoure B (2015) Multiple roles of the prostaglandin D2 signaling pathway in reproduction. Reproduction 149(1):R49–R58. https://doi.org/10.1530/REP-14-0381

    CAS  Article  PubMed  Google Scholar 

  29. Saito S, Tsuda H, Michimata T (2002) Prostaglandin D2 and reproduction. Am J Reprod Immunol 47(5):295–302

    Article  Google Scholar 

  30. Samy ET, Li JC, Grima J, Lee WM, Silvestrini B, Cheng CY (2000) Sertoli cell prostaglandin D2 synthetase is a multifunctional molecule. Its expression and regulation. Endocrinology 141(2):710–721. https://doi.org/10.1210/endo.141.2.7329

    CAS  Article  PubMed  Google Scholar 

  31. Schell C, Frungieri MB, Albrecht M, Gonzalez-Calvar SI, Köhn FM, Calandra RS, Mayerhofer A (2007) A prostaglandin D2 system in the human testis. Fertil Steril 88(1):233–236. https://doi.org/10.1016/j.fertnstert.2006.11.100

    CAS  Article  PubMed  Google Scholar 

  32. Sorrentino C, Silvestrini B, Braghiroli L, Chung SS, Giacomelli S, Leone MG, Xie Y, Sui Y, Mo M, Cheng CY (1998) Rat prostaglandin D2 synthetase. Its tissue distribution, changes during maturation, and regulation in the testis and epididymis. Biol Reprod 59(4):843–853

    CAS  Article  Google Scholar 

  33. Tanaka T, Urade Y, Kimura H, Eguchi N, Nishikawa A, Hayaishi O (1997) Lipocalin-type prostaglandin D synthase (beta-trace) is a newly recognized type of retinoid transporter. J Biol Chem 272(25):15789–15795

    CAS  Article  Google Scholar 

  34. Tanaka Y, Takizawa M, Igimi S, Amano F (2004) Enhanced release of prostaglandin D2 during re-incubation of RAW 264.7 macrophage-like cells after treatment of both lipopolysaccharide and non-steroidal anti-inflammatory drugs. Biol Pharm Bull 27(7):985–991

    CAS  Article  Google Scholar 

  35. Tokugawa Y, Kunishige I, Kubota Y, Shimoya K, Nobunaga T, Kimura T, Saji F, Murata Y, Eguchi N, Oda H, Urade Y, Hayaishi O (1998) Lipocalin-type prostaglandin D synthase in human male reproductive organs and seminal plasma. Biol Reprod 58(2):600–607

    CAS  Article  Google Scholar 

  36. Ueno R, Honda K, Inoue S, Hayaishi O (1983) Prostaglandin D2, a cerebral sleep-inducing substance in rats. Proc Natl Acad Sci 80(6):1735–1737. https://doi.org/10.1073/pnas.80.6.1735

    CAS  Article  PubMed  Google Scholar 

  37. Ujihara M, Urade Y, Eguchi N, Hayashi H, Ikai K, Hayaishi O (1988) Prostaglandin D2 formation and characterization of its synthetases in various tissues of adult rats. Arch Biochem Biophys 260(2):521–531

    CAS  Article  Google Scholar 

  38. Urade Y, Eguchi N (2002) Lipocalin-type and hematopoietic prostaglandin D synthases as a novel example of functional convergence. Prostaglandins other Lipid Mediat 68-69:375–382

    CAS  Article  Google Scholar 

  39. Urade Y, Hayaishi O (2000a) Biochemical, structural, genetic, physiological, and pathophysiological features of lipocalin-type prostaglandin D synthase. Biochim Biophys Acta 1482(1–2):259–271

    CAS  Article  Google Scholar 

  40. Urade Y, Hayaishi O (2000b) Prostaglandin D synthase. Structure and function. Vitam Horm 58:89–120

    CAS  Article  Google Scholar 

  41. Welter H, Köhn FM, Mayerhofer A (2011) Mast cells in human testicular biopsies from patients with mixed atrophy. Increased numbers, heterogeneity, and expression of cyclooxygenase 2 and prostaglandin D2 synthase. Fertil Steril 96(2):309–313. https://doi.org/10.1016/j.fertnstert.2011.05.035

    CAS  Article  PubMed  Google Scholar 

  42. Winnall WR, Ali U, O'Bryan MK, Hirst JJ, Whiley PAF, Muir JA, Hedger MP (2007) Constitutive expression of prostaglandin-endoperoxide synthase 2 by somatic and spermatogenic cells is responsible for prostaglandin E2 production in the adult rat testis. Biol Reprod 76(5):759–768. https://doi.org/10.1095/biolreprod.106.053124

    CAS  Article  PubMed  Google Scholar 

  43. Zhu H, Ma H, Ni H, Ma X-H, Mills N, Yang Z-M (2004) Expression and regulation of lipocalin-type prostaglandin d synthase in rat testis and epididymis. Biol Reprod 70(4):1088–1095. https://doi.org/10.1095/biolreprod.103.022079

    CAS  Article  Google Scholar 

Download references

Acknowledgments

The financial support of the project by the Dr. Jutta & Dr. Georg Bruns Stiftung is gratefully acknowledged. The authors also would like to thank Dr. Gabi Itter (Sanofi-Aventis, Frankfurt) for providing the beagle dogs and Intervet Pharma R&D, Angers Technopole, France, for provision of the Gonazon® implant. Finally, we are thankful to those people who took the dogs in their custody for their great collaboration.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Sandra Goericke-Pesch.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Statement of the welfare of animals

All applicable national and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted.

Animal experimentation had been approved by the respective authority (permit no. AZ V54-19c20/15c GI18/14, Regierungspräsidium Gießen).

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Körber, H., Goericke-Pesch, S. Expression of prostaglandin (PG) D synthase lipocalin and hematopoietic type and PG D receptor during restart of spermatogenesis following downregulation using a slow release GnRH agonist implant in the dog. Cell Tissue Res 378, 359–370 (2019). https://doi.org/10.1007/s00441-019-03059-x

Download citation

Keywords

  • L-PGDS
  • H-PGDS
  • Prostaglandin
  • Slow release GnRH agonist implant