Expression and distribution of GPR55 and GPR119 during the development of rat testis

Abstract

G Protein-Coupled Receptors, GPR55 and GPR119 are widely distributed throughout the body and exert important biological functions. However, little is known about their roles in testis. This study aimed to examine the expression and distribution of GPR55 and GPR119 during the development of the rat testis. Sixty male Sprague Dawley rats (180–240 g) were divided into 10 groups as 7, 14, 21, 28, 35, 42, 49, 56, 63, and 70 postnatal days of age (PND) (six animals per group). The testicular expression of GPR55 and GPR119 has been investigated by immunohistochemistry, Western blot, and quantitative RT-PCR methods. We observed that GPR55 and GPR119 are expressed throughout the rat testis development from PND 7 to 70. However, no difference was observed between the groups in terms of expression levels, except for GPR55 mRNA expression in the group of PND 7. Immunohistochemistry analysis showed that GPR55 is expressed in spermatids and spermatocytes in the mid-term tubules and spermatocytes in the late-stage tubules in groups of PND 56, 63, and 70. For GPR119, very intense positivity was observed only in spermatids in the mid-term (stage VII-VIII) tubules in the groups of PND 56, 63, and 70. No significant difference was observed in the number of GPR55 and GPR119 positive cells in testes from PND 56 through PND 70. Taken together, both GPR55 and GPR119 receptors are expressed throughout the rat testis development (PND 7 to 70). These results suggest that GPR55 and GPR119 are involved in the modulation of male reproductive function.

Keywords

• Expression
• GPR55
• GRP119
• Rat
• Testis

References

1. Amoako AA, Marczylo EL, Willets JM, et al (2011): Differential expression of the orphan G-protein coupled receptor Gpr55 in human spermatozoa. 67th Annual Meeting of the American Society for Reproductive Medicine, Orlando, FL, United States, 15-19 October 2011. Philadelphia, PA, United States: Elsevier Inc.
2. Amoako AA, Willets JM, Marczylo TH, et al (2011): Activation of GPR55 by palmitoylethanolamide increases human sperm motility. 58th Annual Scientific Meeting of the Society for Gynecologic Investigation (SGI), Miami Beach, FL, United States, 16-19 March 2011. Thousand Oaks, CA, United States: Sage Publications.
3. Amoako AA, Marczylo TH, Elson J, et al (2014): Relationship between seminal plasma levels of anandamide congeners palmitoylethanolamide and oleoylethanolamide and semen quality. Fertil Steril, 102, 1260-1267.
4. Andradas C, Caffarel MM, Perez-Gomez E, et al (2011): The orphan G protein-coupled receptor GPR55 promotes cancer cell proliferation via ERK. Oncogene, 30, 245-252.
5. Catanzaro G, Battista N, Rossi G, et al (2011): Effect of capacitation on the endocannabinoid system of mouse sperm. Mol Cell Endocrinol, 343, 88-92.
6. Cherif H, Argaw A, Cécyre B, et al (2015): Role of GPR55 during axon growth and target innervation. Eneuro, 2, 1-20.
7. Chiurchiù V, Lanuti M, De Bardi M, et al (2015): The differential characterization of GPR55 receptor in human peripheral blood reveals a distinctive expression in monocytes and NK cells and a proinflammatory role in these innate cells. Int Immunol, 27, 153-160.
8. Chu ZL, Carroll C, Alfonso J, et al (2008): A role for intestinal endocrine cell-expressed g protein-coupled receptor 119 in glycemic control by enhancing glucagon-like Peptide-1 and glucose-dependent insulinotropic Peptide release. Endocrinology, 149, 2038-2047.

9. Cobellis G, Cacciola G, Scarpa D, et al (2006): Endocannabinoid system in frog and rodent testis: type-1 cannabinoid receptor and fatty acid amide hydrolase activity in male germ cells. Biol Reprod, 75, 82-89.
10. Creasy DM (1997): Evaluation of testicular toxicity in safety evaluation studies: the appropriate use of spermatogenic staging. Toxicol Pathol, 25, 119–131.
11. Fujimoto GI, Morrill GA, O’Connell ME, et al (1982): Effects of cannabinoids given orally and reduced appetite on the male rat reproductive system. Pharmacology, 24, 303–313.
12. Fyfe MC, McCormac JG, Overton HA, et al (2008): GPR119 agonists as potential new oral agents for the treatment of type 2 diabetes and obesity. Expert Opin Drug Discov, 3, 403-413.
13. Godlewski G, Offertáler L, Wagner JA, et al (2009): Receptors for acylethanolamides—GPR55 and GPR119. Prostaglandins Other Lipid Mediat, 89, 105-111.
14. Gorzalka BB, Dang SS (2012): Minireview: Endocannabinoids and Gonadal Hormones: Bidirectional Interactions in Physiology and Behavior. Endocrinology, 153, 1016-1024.
15. Grimaldi P, Orlando P, Di Siena S, et al (2009): The endocannabinoid system and pivotal role of the CB2 receptor in mouse spermatogenesis. Proc Natl Acad Sci USA, 106, 11131–11136.
16. Grimaldi P, Di Giacomo D, Geremia R (2013) The endocannabinoid system and spermatogenesis. Front Endocrinol, 4, 192.
17. Acharyya S (2021). Immune and endocrine aspects of the testis and its relation to male infertility. Chem Biol Lett, 8, 144-161.
18. Henstidge CM, Balenga NA, Ford LA, et al (2009): The GPR55 ligand L‐α‐lysophosphatidylinositol promotes RhoA‐dependent Ca2+ signaling and NFAT activation. The FASEB Journal, 23, 183-193.
19. Hiley CR, Kaup SS (2007): GPR55 and the vascular receptors for cannabinoids. Br J Pharmacol, 152, 559-561.
20. Huan Y, Jiang Q, Li G, et al (2017): The dual DPP4 inhibitor and GPR119 agonist HBK001 regulates glycemic control and beta cell function ex and in vivo. Sci Rep, 7, 1-11.
21. Im DS (2021): GPR119 and GPR55 as Receptors for Fatty Acid Ethanolamides, Oleoylethanolamide and Palmitoylethanolamide. Int J Mol Sci, 22, 1034.
22. Im JH, Kang KW, Kim SY, et al (2018): GPR119 agonist enhances gefitinib responsiveness through lactate-mediated inhibition of autophagy. J Exp Clin Cancer Res, 37, 1-15.
23. Imbernon M, Whyte L, Diaz-Arteaga A, et al (2014): Regulation of GPR55 in rat white adipose tissue and serum LPI by nutritional status, gestation, gender and pituitary factors. Mol Cell Endocrinol, 383, 159-169.
24. Irving A, Abdulrazzaq G, Chan SL, et al (2017): Cannabinoid receptor-related orphan G protein-coupled receptors. Adv Pharmacol, 80, 223-247.
25. Kargl J, Brown AJ, Andersen L, et al (2013): A selective antagonist reveals a potential role of G protein–coupled receptor 55 in platelet and endothelial cell function. J Pharmacol Exp Ther, 346, 54-66.
26. Khanehzad M, Abbaszadeh R, Holakuyee M, et al (2021): FSH regulates RA signaling to commit spermatogonia into differentiation pathway and meiosis. Reprod Biol Endocrinol, 19, 1-19.
27. Kremshofer J, Siwetz M, Berghold VM, et al (2015): A role for GPR55 in human placental venous endothelial cells. Histochem Cell Biol, 144, 49-58.
28. Lauckner JE, Jensen JB, Chen HY, et al (2008): GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci USA, 105, 2699-2704.
29. Lewis SEM, Paro R, Borriello L, et al (2012): Long‐term use of HU210 adversely affects spermatogenesis in rats by modulating the endocannabinoid system. Int J Androl, 35, 731–740.
30. Maccarrone M, Barboni B, Paradisi A, et al (2005): Characterization of the endocannabinoid system in boar spermatozoa and implications for sperm capacitation and acrosome reaction. J Cell Sci, 118, 4393–4404.
31. Maccarrone M, Rapino C, Francavilla F, et al (2021): Cannabinoid signalling and effects of cannabis on the male reproductive system. Nat Rev Urol, 18, 19-32.
32. Marichal-Cancino BA, Fajardo-Valdez A, Ruiz-Contreras AE, et al (2017): Advances in the Physiology of GPR55 in the Central Nervous System. Curr Neuropharmacol, 15, 771–778.
33. Murphy LL, Steger RW, Smith S, et al (1990): Effects of delta-9-tetrahydrocannabinol, cannabinol and cannabidiol, alone and in combinations, on luteinizing hormone and prolactin release and on hypothalamic neurotransmitters in the male rat. Neuroendocrinology, 52, 316-321.
34. Odori S, Hosoda K, Tomita T, et al (2013): GPR119 expression in normal human tissues and islet cell tumors: evidence for its islet-gastrointestinal distribution, expression in pancreatic beta and alpha cells, and involvement in islet function. Metabolism, 62, 70-78.
35. Oka S, Kimura S, Toshida T, et al (2010): Lysophosphatidylinositol induces rapid phosphorylation of p38 mitogen-activated protein kinase and activating transcription factor 2 in HEK293 cells expressing GPR55 and IM-9 lymphoblastoid cells. J Biochem, 147, 671-678.
36. Overton HA, Fyfe MCT, Reynet C (2008): GPR119, a novel G protein‐coupled receptor target for the treatment of type 2 diabetes and obesity. Br J Pharmacol, 153, 76-81.
37. Patil KC, McPherson L, Daly CJ (2015): Co-localization of alpha1-adrenoceptors and GPR55: a novel prostate cancer paradigm? J Pharm Pharmacol, 6, 212-220.
38. Payne KS, Mazur DJ, Hotaling JM, et al (2019): Cannabis and male fertility: a systematic review. J Urol, 202, 674–681.
39. Pertwee RG, Howlett AC, Abood ME, et al (2010): International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB1 and CB2. Pharmacol Rev, 62, 588-631.
40. Ryberg E, Larsson N, Sjögren S, et al (2007): The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol, 152, 1092-1101.
41. Sakamoto Y, Inoue H, Kawakami S, et al (2006): Expression and distribution of Gpr119 in the pancreatic islets of mice and rats: predominant localization in pancreatic polypeptide-secreting PP-cells. Biochem Biophys Res Commun, 351, 474-480.
42. Shi QX, Yang LK, Shi WL, et al (2017): The novel cannabinoid receptor GPR55 mediates anxiolytic-like effects in the medial orbital cortex of mice with acute stress. Mol Brain, 10, 1-11.
43. Soga T, Ohishi T, Matsui T, et al (2005): Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor. Biochem Biophys Res Commun, 326, 744-751.
44. Staton PC, Hatcher JP, Walker DJ, et al (2008): The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain. Pain, 139, 225-236.
45. Sugiura T, Kondo S, Sukagawa A, et al (1996): Enzymatic synthesis of anandamide, an endogenous cannabinoid receptor ligand, through N-acylphosphatidylethanolamine pathway in testis: involvement of Ca2+-dependent transacylase and phosphodiesterase activities. Biochem Biophys Res Commun, 218, 113-117.
46. Wenger T, Ledent C, Csernus V, et al (2001): The central cannabinoid receptor inactivation suppresses endocrine reproductive functions. Biochem Biophys Res Commun, 284, 363–368.
47. Whyte LS, Ryberg E, Sims NA, et al (2009): The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo. Proc Natl Acad Sci USA, 106, 16511-16516.
48. Yang H, Zhou J, Lehmann C (2016): GPR55–a putative “type 3” cannabinoid receptor in inflammation. J Basic Clin Physiol Pharmacol, 27, 297-302.
49. Yu Y, Fuscoe JC, Zhao C, el al (2014): A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages. Nat Commun, 5, 1-11.
50. Zhang X, Maor Y, Wang JF, et al (2010): Endocannabinoid‐like N‐arachidonoyl serine is a novel pro‐angiogenic mediator. Br J Pharmacol, 160, 1583-1594.
51. Zhao J, Zhao Y, Hu Y, et al (2021): Targeting the GPR119/incretin axis: a promising new therapy for metabolic-associated fatty liver disease. Cell Mol Biol Lett, 26, 1-28.