Skip to main content

Advertisement

SpringerLink
Log in

TRPV1 in male reproductive system: focus on sperm function

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The transient receptor potential vanilloid 1 (TRPV1) is a receptor used to perceive external noxious stimuli and participates in the regulation of various pathophysiological mechanisms in vivo by integrating multiple signals. The explosive growth in knowledge of TRPV1 stemmed from research on neuronal pain and heat sensation over the last decades and is being expanded tremendously in peripheral tissue research. The discovery that TRPV1 is functionally active in male animal and human reproductive tissues have attracted increasing attention in recent years. Indeed, many studies have indicated that TRPV1 is an endocannabinoid receptor that mediates Anandamide’s regulation of sperm function. Other characteristics of the TRPV1 channel itself, such as calcium penetration and temperature sensitivity, have also been investigated, especially the possibility that TRPV1 could act as a mediator for sperm thermotaxis. In addition, some reproductive diseases appear to be related to the protective effects of TRPV1 on oxidative stress and heat stress. A better understanding of TRPV1 in these areas should provide strategies for tackling male infertility. This paper is the first to review the expression and mechanism of TRPV1 in the male reproductive system from molecular and cellular perspectives. A focus is given on sperm function, including calcium homeostasis, crosstalk with endocannabinoid system, participation in cholesterol-related sperm maturation, and thermotaxis, hoping to capture the current situation of this rapidly developing field.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The datasets analyzed during the current study are available in the PDB database and GEO database, https://www.rcsb.org/structure/7L2O, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4818, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4193.

References

  1. Suarez SS, Pacey AA (2006) Sperm transport in the female reproductive tract. Hum Reprod Update 12:23–37. https://doi.org/10.1093/humupd/dmi047

    Article  CAS  PubMed  Google Scholar 

  2. Sun H, Gong TT, Jiang YT, Zhang S, Zhao YH, Wu QJ (2019) Global, regional, and national prevalence and disability-adjusted life-years for infertility in 195 countries and territories, 1990–2017: results from a global burden of disease study, 2017. Aging 11:10952–10991. https://doi.org/10.18632/aging.102497

    Article  PubMed  PubMed Central  Google Scholar 

  3. Miller D, Vukina J (2020) Recent advances in clinical diagnosis and treatment of male factor infertility. Postgrad Med 132:28–34. https://doi.org/10.1080/00325481.2020.1830589

    Article  PubMed  Google Scholar 

  4. Agarwal A, Baskaran S, Parekh N, Cho CL, Henkel R, Vij S, Arafa M, Panner Selvam MK, Shah R (2021) Male infertility. Lancet 397:319–333. https://doi.org/10.1016/s0140-6736(20)32667-2

    Article  PubMed  Google Scholar 

  5. Yang F, Zheng J (2017) Understand spiciness: mechanism of TRPV1 channel activation by capsaicin. Protein Cell 8:169–177. https://doi.org/10.1007/s13238-016-0353-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Muller C, Morales P, Reggio PH (2019) Cannabinoid ligands targeting TRP channels. Front Mol Neurosci. https://doi.org/10.3389/fnmol.2018.00487

    Article  PubMed  PubMed Central  Google Scholar 

  7. Gracia Gervasi M, Osycka-Salut C, Caballero J, Vazquez-Levin M, Pereyra E, Billi S, Franchi A, Perez-Martinez S (2011) Anandamide capacitates bull spermatozoa through CB1 and TRPV1 activation. PLoS ONE. https://doi.org/10.1371/journal.pone.0016993

    Article  Google Scholar 

  8. Yan Y, Zhang B, Fu Q, Wu J, Liu R (2021) A fully integrated biomimetic microfluidic device for evaluation of sperm response to thermotaxis and chemotaxis. Lab Chip. https://doi.org/10.1039/d0lc00845a

    Article  PubMed  PubMed Central  Google Scholar 

  9. Voets T, Droogmans G, Wissenbach U, Janssens A, Flockerzi V, Nilius B (2004) The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels. Nature 430:748–754. https://doi.org/10.1038/nature02732

    Article  CAS  PubMed  Google Scholar 

  10. Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21:531–543. https://doi.org/10.1016/s0896-6273(00)80564-4

    Article  CAS  PubMed  Google Scholar 

  11. Nilius B, Szallasi A (2014) Transient receptor potential channels as drug targets: from the science of basic research to the art of medicine. Pharmacol Rev 66:676–814. https://doi.org/10.1124/pr.113.008268

    Article  CAS  PubMed  Google Scholar 

  12. Kaneko Y, Szallasi A (2014) Transient receptor potential (TRP) channels: a clinical perspective. Br J Pharmacol 171:2474–2507. https://doi.org/10.1111/bph.12414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Moran MM (2018) TRP channels as potential drug targets. Annu Rev Pharmacol Toxicol 58:309–329. https://doi.org/10.1146/annurev-pharmtox-010617-052832

    Article  CAS  PubMed  Google Scholar 

  14. Vandewauw I, De Clercq K, Mulier M, Held K, Pinto S, Van Ranst N, Segal A, Voet T, Vennekens R, Zimmermann K, Vriens J, Voets T (2018) A TRP channel trio mediates acute noxious heat sensing. Nature 555:662–666. https://doi.org/10.1038/nature26137

    Article  CAS  PubMed  Google Scholar 

  15. Cao E, Liao M, Cheng Y, Julius D (2013) TRPV1 structures in distinct conformations reveal activation mechanisms. Nature 504:113–118. https://doi.org/10.1038/nature12823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Liao M, Cao E, Julius D, Cheng Y (2013) Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 504:107–112. https://doi.org/10.1038/nature12822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Gao Y, Cao E, Julius D, Cheng Y (2016) TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action. Nature 534:347–351. https://doi.org/10.1038/nature17964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhang K, Julius D, Cheng Y (2021) Structural snapshots of TRPV1 reveal mechanism of polymodal functionality. Cell. https://doi.org/10.1016/j.cell.2021.08.012

    Article  PubMed  PubMed Central  Google Scholar 

  19. Stein RJ, Santos S, Nagatomi J, Hayashi Y, Minnery BS, Xavier M, Patel AS, Nelson JB, Futrell WJ, Yoshimura N, Chancellor MB, De Miguel F (2004) Cool (TRPM8) and hot (TRPV1) receptors in the bladder and male genital tract. J Urol 172:1175–1178. https://doi.org/10.1097/01.ju.0000134880.55119.cf

    Article  CAS  PubMed  Google Scholar 

  20. Maccarrone M, Barboni B, Paradisi A, Bernabo N, Gasperi V, Pistilli MG, Fezza F, Lucidi P, Mattioli M (2005) Characterization of the endocannabinoid system in boar spermatozoa and implications for sperm capacitation and acrosome reaction. J Cell Sci 118:4393–4404. https://doi.org/10.1242/jcs.02536

    Article  CAS  PubMed  Google Scholar 

  21. Auzanneau C, Norez C, Antigny F, Thoreau V, Jougla C, Cantereau A, Becq F, Vandebrouck C (2008) Transient receptor potential vanilloid 1 (TRPV1) channels in cultured rat Sertoli cells regulate an acid sensing chloride channel. Biochem Pharmacol 75:476–483. https://doi.org/10.1016/j.bcp.2007.09.004

    Article  CAS  PubMed  Google Scholar 

  22. Francavilla F, Battista N, Barbonetti A, Vassallo MRC, Rapino C, Antonangelo C, Pasquariello N, Catanzaro G, Barboni B, Maccarrone M (2009) Characterization of the endocannabinoid system in human spermatozoa and involvement of transient receptor potential vanilloid 1 receptor in their fertilizing ability. Endocrinology 150:4692–4700. https://doi.org/10.1210/en.2009-0057

    Article  CAS  PubMed  Google Scholar 

  23. Catanzaro G, Battista N, Rossi G, Di Tommaso M, Pucci M, Pirazzi V, Cecconi S, Maccarrone M (2011) Effect of capacitation on the endocannabinoid system of mouse sperm. Mol Cell Endocrinol 343:88–92. https://doi.org/10.1016/j.mce.2011.01.022

    Article  CAS  PubMed  Google Scholar 

  24. Majhi RK, Kumar A, Yadav M, Swain N, Kumari S, Saha A, Pradhan A, Goswami L, Saha S, Samanta L, Maity A, Nayak TK, Chattopadhyay S, Rajakuberan C, Kumar A, Goswami C (2013) Thermosensitive ion channel TRPV1 is endogenously expressed in the sperm of a fresh water teleost fish (Labeo rohita) and regulates sperm motility. Channels 7:483–492. https://doi.org/10.4161/chan.25793

    Article  PubMed  PubMed Central  Google Scholar 

  25. Majhi RK, Kumar A, Giri SC, Goswami C (2020) Differential expression and localization of TRPV channels in the mature sperm of anas platyrhynchos. Reprod Domest Anim 55:1619–1628. https://doi.org/10.1111/rda.13822

    Article  CAS  PubMed  Google Scholar 

  26. Grimaldi P, Orlando P, Di Siena S, Lolicato F, Petrosino S, Bisogno T, Geremia R, De Petrocellis L, Di Marzo V (2009) The endocannabinoid system and pivotal role of the CB2 receptor in mouse spermatogenesis. Proc Natl Acad Sci USA 106:11131–11136. https://doi.org/10.1073/pnas.0812789106

    Article  PubMed  PubMed Central  Google Scholar 

  27. Bernabo N, Pistilli MG, Mattioli M, Barboni B (2010) Role of TRPV1 channels in boar spermatozoa acquisition of fertilizing ability. Mol Cell Endocrinol 323:224–231. https://doi.org/10.1016/j.mce.2010.02.025

    Article  CAS  PubMed  Google Scholar 

  28. Darszon A, Nishigaki T, Beltran C, Treviño CL (2011) Calcium channels in the development, maturation, and function of spermatozoa. Physiol Rev 91:1305–1355. https://doi.org/10.1152/physrev.00028.2010

    Article  CAS  PubMed  Google Scholar 

  29. Lishko PV, Kirichok Y, Ren D, Navarro B, Chung JJ, Clapham DE (2012) The control of male fertility by spermatozoan ion channels. Annu Rev Physiol 74:453–475. https://doi.org/10.1146/annurev-physiol-020911-153258

    Article  CAS  PubMed  Google Scholar 

  30. Krasznai Z, Marian T, Izumi H, Damjanovich S, Balkay L, Tron L, Morisawa M (2000) Membrane hyperpolarization removes inactivation of Ca2+ channels, leading to Ca2+ influx and subsequent initiation of sperm motility in the common carp. Proc Natl Acad Sci USA 97:2052–2057. https://doi.org/10.1073/pnas.040558097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Nowicka-Bauer K, Szymczak-Cendlak M (2021) Structure and function of ion channels regulating sperm motility-an overview. Int J Mol Sci. https://doi.org/10.3390/ijms22063259

    Article  PubMed  PubMed Central  Google Scholar 

  32. Quill TA, Sugden SA, Rossi KL, Doolittle LK, Hammer RE, Garbers DL (2003) Hyperactivated sperm motility driven by CatSper2 is required for fertilization. Proc Natl Acad Sci USA 100:14869–14874. https://doi.org/10.1073/pnas.2136654100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Carlson AE, Westenbroek RE, Quill T, Ren D, Clapham DE, Hille B, Garbers DL, Babcock DF (2003) CatSper1 required for evoked Ca2+ entry and control of flagellar function in sperm. Proc Natl Acad Sci USA 100:14864–14868. https://doi.org/10.1073/pnas.2536658100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Negri L, Lattanzi R, Giannini E, Colucci M, Margheriti F, Melchiorri P, Vellani V, Tian H, De Felice M, Porreca F (2006) Impaired nociception and inflammatory pain sensation in mice lacking the prokineticin receptor PKR1: focus on interaction between PKR1 and the capsaicin receptor TRPV1 in pain behavior. J Neurosci 26:6716–6727. https://doi.org/10.1523/Jneurosci.5403-05.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. De Toni L, Garolla A, Menegazzo M, Magagna S, Di Nisio A, Sabovic I, Rocca MS, Scattolini V, Filippi A, Foresta C (2016) Heat sensing receptor TRPV1 Is a mediator of thermotaxis in human spermatozoa. PLoS ONE. https://doi.org/10.1371/journal.pone.0167622

    Article  PubMed  PubMed Central  Google Scholar 

  36. Wisnoskey BJ, Sinkins WG, Schilling WP (2003) Activation of vanilloid receptor type I in the endoplasmic reticulum fails to activate store-operated Ca2+ entry. Biochem J 372:517–528. https://doi.org/10.1042/BJ20021574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wen W, Que K, Zang C, Wen J, Sun G, Zhao Z, Li Y (2017) Expression and distribution of three transient receptor potential vanilloid(TRPV) channel proteins in human odontoblast-like cells. J Mol Histol 48:367–377. https://doi.org/10.1007/s10735-017-9735-2

    Article  CAS  PubMed  Google Scholar 

  38. Chen Y, Wang H, Wang F, Chen C, Zhang P, Song D, Luo T, Xu H, Zeng X (2020) Sperm motility modulated by Trpv1 regulates zebrafish fertilization. Theriogenology 151:41–51. https://doi.org/10.1016/j.theriogenology.2020.03.032

    Article  CAS  PubMed  Google Scholar 

  39. Gervasi MG, Osycka-Salut C, Sanchez T, Alonso CAI, Llados C, Castellano L, Franchi AM, Villalon M, Perez-Martinez S (2016) Sperm release from the oviductal epithelium depends on Ca2+ Influx upon activation of CB1 and TRPV1 by anandamide. J Cell Biochem 117:320–333. https://doi.org/10.1002/jcb.25273

    Article  CAS  PubMed  Google Scholar 

  40. Mundt N, Spehr M, Lishko PV (2018) TRPV4 is the temperature-sensitive ion channel of human sperm. Elife. https://doi.org/10.7554/eLife.35853

    Article  PubMed  PubMed Central  Google Scholar 

  41. Bahat A, Eisenbach M (2010) Human sperm thermotaxis is mediated by phospholipase C and inositol trisphosphate receptor Ca2+ channel. Biol Reprod 82:606–616. https://doi.org/10.1095/biolreprod.109.080127

    Article  CAS  PubMed  Google Scholar 

  42. Pacher P, Kogan NM, Mechoulam R (2020) Beyond THC and endocannabinoids. Annu Rev Pharmacol Toxicol 60:637–659. https://doi.org/10.1146/annurev-pharmtox-010818-021441

    Article  CAS  PubMed  Google Scholar 

  43. Maccarrone M, Bab R, Biro T, Cabral GA, Dey SK, Di Marzo V, Konje JC, Kunos G, Mechoulam R, Pacher P, Sharkey KA, Zimmer A (2015) Endocannabinoid signaling at the periphery: 50 years after THC. Trends Pharmacol Sci 36:277–296. https://doi.org/10.1016/j.tips.2015.02.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Lu H-C, Mackie K (2016) An introduction to the endogenous cannabinoid system. Biol Psychiat 79:516–525. https://doi.org/10.1016/j.biopsych.2015.07.028

    Article  CAS  PubMed  Google Scholar 

  45. Harclerode J, Nyquist SE, Nazar B, Lowe D (1978) Effects of cannabis on sex hormones and testicular enzymes of the rodent. Adv Biosci 22–23:395–405. https://doi.org/10.1016/b978-0-08-023759-6.50035-4

    Article  PubMed  Google Scholar 

  46. Schuel H, Burkman LJ, Lippes J, Crickard K, Forester E, Piomelli D, Giuffrida A (2002) N-Acylethanolamines in human reproductive fluids. Chem Phys Lipid 121:211–227. https://doi.org/10.1016/s0009-3084(02)00158-5

    Article  CAS  Google Scholar 

  47. Amoako AA, Marczylo TH, Lam PM, Willets JM, Derry A, Elson J, Konje JC (2010) Quantitative analysis of anandamide and related acylethanolamides in human seminal plasma by ultra performance liquid chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 878:3231–3237. https://doi.org/10.1016/j.jchromb.2010.09.024

    Article  CAS  PubMed  Google Scholar 

  48. Gervasi MG, Marczylo TH, Lam PM, Rana S, Franchi AM, Konje JC, Perez-Martinez S (2013) Anandamide levels fluctuate in the bovine oviduct during the oestrous cycle. PLoS ONE 8:e72521. https://doi.org/10.1371/journal.pone.0072521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Amoako AA, Marczylo TH, Elson J, Taylor AH, Willets JM, Konje JC (2014) Relationship between seminal plasma levels of anandamide congeners palmitoylethanolamide and oleoylethanolamide and semen quality. Fertil Steril 102:1260–1267. https://doi.org/10.1016/j.fertnstert.2014.07.767

    Article  CAS  PubMed  Google Scholar 

  50. Zufferey F, Donzé N, Rahban R, Senn A, Stettler E, Rudaz S, Nef S, Rossier MF (2020) Semen endocannabinoids are correlated to sperm quality in a cohort of 200 young Swiss men. Andrology 8:1126–1135. https://doi.org/10.1111/andr.12785

    Article  CAS  PubMed  Google Scholar 

  51. Amoako AA, Marczylo TH, Marczylo EL, Elson J, Willets JM, Taylor AH, Konje JC (2013) Anandamide modulates human sperm motility: implications for men with asthenozoospermia and oligoasthenoteratozoospermia. Hum Reprod 28:2058–2066. https://doi.org/10.1093/humrep/det232

    Article  CAS  PubMed  Google Scholar 

  52. Morris A (2019) The endocannabinoid system in human testes. Nat Rev Endocrinol 15:684–685. https://doi.org/10.1038/s41574-019-0271-x

    Article  CAS  PubMed  Google Scholar 

  53. Nielsen JE, Rolland AD, Rajpert-De Meyts E, Janfelt C, Jørgensen A, Winge SB, Kristensen DM, Juul A, Chalmel F, Jégou B, Skakkebaek NE (2019) Characterisation and localisation of the endocannabinoid system components in the adult human testis. Sci Rep 9:12866. https://doi.org/10.1038/s41598-019-49177-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Bovolin P, Cottone E, Pomatto V, Fasano S, Pierantoni R, Cobellis G, Meccariello R (2014) Endocannabinoids are involved in male vertebrate reproduction: regulatory mechanisms at central and gonadal level. Front Endocrinol 5:54. https://doi.org/10.3389/fendo.2014.00054

    Article  Google Scholar 

  55. Schuel H, Goldstein E, Mechoulam R, Zimmerman AM, Zimmerman S (1994) Anandamide (arachidonylethanolamide), a brain cannabinoid receptor agonist, reduces sperm fertilizing capacity in sea urchins by inhibiting the acrosome reaction. Proc Natl Acad Sci U S A 91:7678–7682. https://doi.org/10.1073/pnas.91.16.7678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lewis SEM, Rapino C, Di Tommaso M, Pucci M, Battista N, Paro R, Simon L, Lutton D, Maccarrone M (2012) Differences in the endocannabinoid system of sperm from fertile and infertile men. PLoS ONE. https://doi.org/10.1371/journal.pone.0047704

    Article  PubMed  PubMed Central  Google Scholar 

  57. Pistilli MG, Bernabo N, Lucidi P, Di Giacinto O, Di Pancrazio C, Paradisi A, Maccarrone M, Barboni B (2006) Role of the endogenous cannabinoid system on function of boar spermatozoa. Vet Res Commun 30:195–198. https://doi.org/10.1007/s11259-006-0039-3

    Article  Google Scholar 

  58. De Petrocellis L, Bisogno T, Maccarrone M, Davis JB, Finazzi-Agro A, Di Marzo V (2001) The activity of anandamide at vanilloid VR1 receptors requires facilitated transport across the cell membrane and is limited by intracellular metabolism. J Biol Chem 276:12856–12863. https://doi.org/10.1074/jbc.M008555200

    Article  PubMed  Google Scholar 

  59. Rossato M, Ion Popa F, Ferigo M, Clari G, Foresta C (2005) Human sperm express cannabinoid receptor Cb1, the activation of which inhibits motility, acrosome reaction, and mitochondrial function. J Clin Endocrinol Metab 90:984–991. https://doi.org/10.1210/jc.2004-1287

    Article  CAS  PubMed  Google Scholar 

  60. Bernabò N, Palestini P, Chiarini M, Maccarrone M, Mattioli M, Barboni B (2012) Endocannabinoid-binding CB1 and TRPV1 receptors as modulators of sperm capacitation. Commun Integr Biol 5:68–70. https://doi.org/10.4161/cib.18118

    Article  PubMed  PubMed Central  Google Scholar 

  61. Martínez-León E, Osycka-Salut C, Signorelli J, Kong M, Morales P, Pérez-Martínez S, Díaz ES (2019) Fibronectin modulates the endocannabinoid system through the cAMP/PKA pathway during human sperm capacitation. Mol Reprod Dev 86:224–238. https://doi.org/10.1002/mrd.23097

    Article  CAS  PubMed  Google Scholar 

  62. Osycka-Salut CE, Martinez-Leon E, Gervasi MG, Castellano L, Davio C, Chiarante N, Franchi AM, Ribeiro ML, Diaz ES, Perez-Martinez S (2020) Fibronectin induces capacitation-associated events through the endocannabinoid system in bull sperm. Theriogenology 153:91–101. https://doi.org/10.1016/j.theriogenology.2020.04.031

    Article  CAS  PubMed  Google Scholar 

  63. Chen J, Varga A, Selvarajah S, Jenes A, Dienes B, Sousa-Valente J, Kulik A, Veress G, Brain SD, Baker D, Urban L, Mackie K, Nagy I (2016) Spatial distribution of the cannabinoid type 1 and capsaicin receptors may contribute to the complexity of their crosstalk. Sci Rep. https://doi.org/10.1038/srep33307

    Article  PubMed  PubMed Central  Google Scholar 

  64. De Petrocellis L, Di Marzo V (2009) Role of endocannabinoids and endovanilloids in Ca2+ signalling. Cell Calcium 45:611–624. https://doi.org/10.1016/j.ceca.2009.03.003

    Article  CAS  PubMed  Google Scholar 

  65. Prescott ED, Julius D (2003) A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity. Science 300:1284–1288. https://doi.org/10.1126/science.1083646

    Article  CAS  PubMed  Google Scholar 

  66. Keber R, Rozman D, Horvat S (2013) Sterols in spermatogenesis and sperm maturation. J Lipid Res 54:20–33. https://doi.org/10.1194/jlr.R032326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Haidl G, Opper C (1997) Changes in lipids and membrane anisotropy in human spermatozoa during epididymal maturation. Hum Reprod 12:2720–2723. https://doi.org/10.1093/humrep/12.12.2720

    Article  CAS  PubMed  Google Scholar 

  68. Moon KH, Bunge RG (1970) Observations on the biochemistry of human semen. 4. cholesterol. Cholesterol Fertility and Sterility 21:80–000. https://doi.org/10.1016/s0015-0282(16)37272-7

    Article  CAS  PubMed  Google Scholar 

  69. Buffone MG, Verstraeten SV, Calamera JC, Doncel GF (2009) High cholesterol content and decreased membrane fluidity in human spermatozoa are associated with protein tyrosine phosphorylation and functional deficiencies. J Androl 30:552–558. https://doi.org/10.2164/jandrol.108.006551

    Article  CAS  PubMed  Google Scholar 

  70. Visconti PE, Galantino-Homer H, Ning XP, Moore GD, Valenzuela JP, Jorgez CJ, Alvarez JG, Kopf GS (1999) Cholesterol efflux-mediated signal transduction in mammalian sperm-beta-cyclodextrins initiate transmembrane signaling leading to an increase in protein tyrosine phosphorylation and capacitation. J Biol Chem 274:3235–3242. https://doi.org/10.1074/jbc.274.5.3235

    Article  CAS  PubMed  Google Scholar 

  71. Levitan I, Christian AE, Tulenko TN, Rothblat GH (2000) Membrane cholesterol content modulates activation of volume-regulated anion current in bovine endothelial cells. J Gen Physiol 115:405–416. https://doi.org/10.1085/jgp.115.4.405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Jansson ET, Trkulja CL, Ahemaiti A, Millingen M, Jeffries GDM, Jardemark K, Orwar O (2013) Effect of cholesterol depletion on the pore dilation of TRPV1. Mol Pain. https://doi.org/10.1186/1744-8069-9-1

    Article  PubMed  PubMed Central  Google Scholar 

  73. Liu M, Huang W, Wu D, Priestley JV (2006) TRPV1, but not P2X, requires cholesterol for its function and membrane expression in rat nociceptors. Eur J Neurosci 24:1–6. https://doi.org/10.1111/j.1460-9568.2006.04889.x

    Article  CAS  PubMed  Google Scholar 

  74. Botto L, Bernabò N, Palestini P, Barboni B (2010) Bicarbonate induces membrane reorganization and CBR1 and TRPV1 endocannabinoid receptor migration in lipid microdomains in capacitating boar spermatozoa. J Membr Biol 238:33–41. https://doi.org/10.1007/s00232-010-9316-8

    Article  CAS  PubMed  Google Scholar 

  75. De Toni L, Sabovic I, De Filippis V, Acquasaliente L, Peterle D, Guidolin D, Sut S, Di Nisio A, Foresta C, Garolla A (2021) Sperm cholesterol content modifies sperm function and TRPV1-mediated sperm migration. Int J Mol Sci. https://doi.org/10.3390/ijms22063126

    Article  PubMed  PubMed Central  Google Scholar 

  76. Picazo-Juarez G, Romero-Suarez S, Nieto-Posadas A, Llorente I, Jara-Oseguera A, Briggs M, McIntosh TJ, Simon SA, Ladron-de-Guevara E, Islas LD, Rosenbaum T (2011) Identification of a binding motif in the S5 Helix that confers cholesterol sensitivity to the TRPV1 Ion channel. J Biol Chem 286:24966–24976. https://doi.org/10.1074/jbc.M111.237537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Fantini J, Barrantes FJ (2013) How cholesterol interacts with membrane proteins: an exploration of cholesterol-binding sites including CRAC, CARC, and tilted domains. Front Physiol. https://doi.org/10.3389/fphys.2013.00031

    Article  PubMed  PubMed Central  Google Scholar 

  78. Hua T, Li X, Wu L, Iliopoulos-Tsoutsouvas C, Wang Y, Wu M, Shen L, Brust CA, Nikas SP, Song F, Song X, Yuan S, Sun Q, Wu Y, Jiang S, Grim TW, Benchama O, Stahl EL, Zvonok N, Zhao S, Bohn LM, Makriyannis A, Liu ZJ (2020) Activation and signaling mechanism revealed by cannabinoid receptor-gi complex structures. Cell 180(655–665):e18. https://doi.org/10.1016/j.cell.2020.01.008

    Article  CAS  Google Scholar 

  79. Hunter RHF, Nichol R (1986) A preovulatory temperature gradient between the isthmus and ampulla of pig oviducts during the phase of sperm storage. J Reprod Fertil 77:599–606. https://doi.org/10.1530/jrf.0.0770599

    Article  CAS  PubMed  Google Scholar 

  80. Bahat A, Tur-Kaspa I, Gakamsky A, Giojalas LC, Breitbart H, Eisenbach M (2003) Thermotaxis of mammalian sperm cells: a potential navigation mechanism in the female genital tract. Nat Med 9:149–150. https://doi.org/10.1038/nm0203-149

    Article  CAS  PubMed  Google Scholar 

  81. Bahat A, Eisenbach M, Tur-Kaspa I (2005) Periovulatory increase in temperature difference within the rabbit oviduct. Hum Reprod 20:2118–2121. https://doi.org/10.1093/humrep/dei006

    Article  PubMed  Google Scholar 

  82. Bahat A, Caplan SR, Eisenbach M (2012) Thermotaxis of human sperm cells in extraordinarily shallow temperature gradients over a wide range. PLoS ONE. https://doi.org/10.1371/journal.pone.0041915

    Article  PubMed  PubMed Central  Google Scholar 

  83. Eisenbach M, Giojalas LC (2006) Sperm guidance in mammals—an unpaved road to the egg. Nat Rev Mol Cell Biol 7:276–285. https://doi.org/10.1038/nrm1893

    Article  CAS  PubMed  Google Scholar 

  84. Vay L, Gu CJ, McNaughton PA (2012) The thermo-TRP ion channel family: properties and therapeutic implications. Br J Pharmacol 165:787–801. https://doi.org/10.1111/j.1476-5381.2011.01601.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. De Blas GA, Darszon A, Ocampo AY, Serrano CJ, Castellano LE, Hernandez-Gonzalez EO, Chirinos M, Larrea F, Beltran C, Trevino CL (2009) TRPM8, a versatile channel in human sperm. PLoS ONE. https://doi.org/10.1371/journal.pone.0006095

    Article  PubMed  PubMed Central  Google Scholar 

  86. Martinez-Lopez P, Trevino CL, Luis De la Vega-Beltran J, De Blas G, Monroy E, Beltran C, Orta G, Gibbs GM, O’Bryan MK, Darszon A (2011) TRPM8 in mouse sperm detects temperature changes and may influence the acrosome reaction. J Cell Physiol 226:1620–1631. https://doi.org/10.1002/jcp.22493

    Article  CAS  PubMed  Google Scholar 

  87. Kumar A, Majhi RK, Swain N, Giri SC, Kar S, Samanta L, Goswami C (2016) TRPV4 is endogenously expressed in vertebrate spermatozoa and regulates intracellular calcium in human sperm. Biochem Biophys Res Commun 473:781–788. https://doi.org/10.1016/j.bbrc.2016.03.071

    Article  CAS  PubMed  Google Scholar 

  88. Hamano K-i, Kawanishi T, Mizuno A, Suzuki M, Takagi Y (2016) Involvement of transient receptor potential vanilloid (TRPV) 4 in mouse sperm thermotaxis. J Reprod and Dev 62:415–422. https://doi.org/10.1262/jrd.2015-106

    Article  CAS  Google Scholar 

  89. Perez-Cerezales S, Boryshpolets S, Afanzar O, Brandis A, Nevo R, Kiss V, Eisenbach M (2015) Involvement of opsins in mammalian sperm thermotaxis. Sci Rep. https://doi.org/10.1038/srep16146

    Article  PubMed  PubMed Central  Google Scholar 

  90. Roy D, Levi K, Kiss V, Nevo R, Eisenbach M (2020) Rhodopsin and melanopsin coexist in mammalian sperm cells and activate different signaling pathways for thermotaxis. Sci Rep. https://doi.org/10.1038/s41598-019-56846-5

    Article  PubMed  PubMed Central  Google Scholar 

  91. Li Z, Liu W, Qiu T, Xie L, Chen W, Liu R, Lu Y, Mitchelson K, Wang J, Qiao J, Cheng J (2014) The construction of an interfacial valve-based microfluidic chip for thermotaxis evaluation of human sperm. Biomicrofluidics. https://doi.org/10.1063/1.4866851

    Article  PubMed  PubMed Central  Google Scholar 

  92. Jacobsen FM, Rudlang TM, Fode M, Østergren PB, Sønksen J, Ohl DA, Jensen CFS (2020) The impact of testicular torsion on testicular function. World J men’s Health 38:298–307. https://doi.org/10.5534/wjmh.190037

    Article  Google Scholar 

  93. Sarioglu A, Gedikoglu G, Bingol-Kologlu M, Buyukpamukcu N, Tanyel FC (2001) Capsaicin in albino rats prevents contralateral testis from the damaging effects posed by ipsilateral testis that underwent torsion. Eur Urol 40:469–72. https://doi.org/10.1159/000049818 (discussion 472-3)

    Article  CAS  PubMed  Google Scholar 

  94. Srinivasan K (2016) Biological activities of red pepper (Capsicum annuum) and its pungent principle capsaicin: a review. Crit Rev Food Sci Nutr 56:1488–1500. https://doi.org/10.1080/10408398.2013.772090

    Article  CAS  PubMed  Google Scholar 

  95. Perruzza D, Bernabò N, Rapino C, Valbonetti L, Falanga I, Russo V, Mauro A, Berardinelli P, Stuppia L, Maccarrone M, Barboni B (2018) Artificial neural network to predict varicocele impact on male fertility through testicular endocannabinoid gene expression profiles. Biomed Res Int 2018:3591086. https://doi.org/10.1155/2018/3591086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Hosseini M, Tavalaee M, Rahmani M, Eskandari A, Shaygannia E, Kiani-Esfahani A, Zohrabi D, Nasr-Esfahani MH (2020) Capsaicin improves sperm quality in rats with experimental varicocele. Andrologia 52:e13762. https://doi.org/10.1111/and.13762

    Article  CAS  PubMed  Google Scholar 

  97. Ghasemi M, Sadeghipour H, Mani AR, Tavakoli S, Hajrasouliha AR, Ebrahimi F, Dehpour AR (2006) Effect of anandamide on nonadrenergic noncholinergic-mediated relaxation of rat corpus cavernosum. Eur J Pharmacol 544:138–145. https://doi.org/10.1016/j.ejphar.2006.06.002

    Article  CAS  PubMed  Google Scholar 

  98. Ghasemi M, Sadeghipour H, Dehpour AR (2007) Anandamide improves the impaired nitric oxide-mediated neurogenic relaxation of the corpus cavernosum in diabetic rats: involvement of cannabinoid CB1 and vanilloid VR1 receptors. BJU Int 100:1385–1390. https://doi.org/10.1111/j.1464-410X.2007.07180.x

    Article  CAS  PubMed  Google Scholar 

  99. Osycka-Salut C, Gervasi MG, Pereyra E, Cella M, Ribeiro ML, Franchi AM, Perez-Martinez S (2012) Anandamide induces sperm release from oviductal epithelia through nitric oxide pathway in bovines. PLoS ONE 7:e30671. https://doi.org/10.1371/journal.pone.0030671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Park SG, Yon JM, Lin C, Gwon LW, Lee JG, Baek IJ, Lee BJ, Yun YW, Nam SY (2017) Capsaicin attenuates spermatogenic cell death induced by scrotal hyperthermia through its antioxidative and anti-apoptotic activities. Andrologia. https://doi.org/10.1111/and.12656

    Article  PubMed  Google Scholar 

  101. Mizrak SC, van Dissel-Emiliani FM (2008) Transient receptor potential vanilloid receptor-1 confers heat resistance to male germ cells. Fertil Steril 90:1290–1293. https://doi.org/10.1016/j.fertnstert.2007.10.081

    Article  CAS  PubMed  Google Scholar 

  102. Mizrak SC, Gadella BM, Erdost H, Ozer A, van Pelt AMM, van Dissel-Emiliani FMF (2008) Spermatogonial stem cell sensitivity to capsaicin: an in vitro study. Reprod Biol Endocrinol. https://doi.org/10.1186/1477-7827-6-52

    Article  PubMed  PubMed Central  Google Scholar 

  103. Siregar AS, Nyiramana MM, Kim E-J, Shin E-J, Kim C-W, Lee DK, Hong S-G, Han J, Kang D (2019) TRPV1 Is associated with testicular apoptosis in mice. J Anim Reprod Biotechnol 34:311–317

    Article  Google Scholar 

  104. Kumar A, Mishra AK, Singh V, Yadav S, Saxena A, Garg SK, Swain DK (2019) Molecular and functional insights into transient receptor potential vanilloid 1 (TRPV1) in bull spermatozoa. Theriogenology 128:207–217. https://doi.org/10.1016/j.theriogenology.2019.01.029

    Article  CAS  PubMed  Google Scholar 

  105. Rossi G, Gasperi V, Paro R, Barsacchi D, Cecconi S, Maccarrone M (2007) Follicle-stimulating hormone activates fatty acid amide hydrolase by protein kinase A and aromatase-dependent pathways in mouse primary sertoli cells. Endocrinology 148:1431–1439. https://doi.org/10.1210/en.2006-0969

    Article  CAS  PubMed  Google Scholar 

  106. Rossi G, Dufrusine B, Lizzi AR, Luzi C, Piccoli A, Fezza F, Iorio R, D’Andrea G, Dainese E, Cecconi S, Maccarrone M (2020) Bisphenol a deranges the endocannabinoid system of primary sertoli cells with an impact on inhibin B production. Int J Mol Sci. https://doi.org/10.3390/ijms21238986

    Article  PubMed  PubMed Central  Google Scholar 

  107. Pilutin A, Misiakiewicz-Has K, Kolasa A, Baranowska-Bosiacka I, Marchlewicz M, Wiszniewska B (2014) The immunoexpression of androgen receptor, estrogen receptors alpha and beta, vanilloid type 1 receptor and cytochrome p450 aromatase in rats testis chronically treated with letrozole, an aromatase inhibitor. Folia Histochem Cytobiol 52:206–217. https://doi.org/10.5603/fhc.2014.0024

    Article  PubMed  Google Scholar 

Download references

Funding

This work was supported by the Science and technology planning project of Jiangxi Provincial Health and Family Planning Commission Grant No. 20181729 and the Traditional Chinese Medicine Scientific and Technological Program of the Jiangxi Province Grant No. 2021A357.

Author information

Authors and Affiliations

  1. Institute of Life Science and School of Life Science, Nanchang University, No. 999 Xuefu Avenue, Honggutan District, Nanchang, 330031, Jiangxi, People’s Republic of China

    Wanglong Xiao & Ying Chen

  2. Key Laboratory of Reproductive Physiology and Pathology in Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China

    Ying Chen

Authors
  1. Wanglong Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ying Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

WL.X.: Conceptualization and initial draft. Y.C.: Design and supervision, critical revision and suggestions. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ying Chen.

Ethics declarations

Conflict of interest

The authors have no competing interests to declare that are relevant to the content of this article.

Ethical approval

It is not applicable.

Consent to participate

It is not applicable.

Consent for publication

It is not applicable.

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

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xiao, W., Chen, Y. TRPV1 in male reproductive system: focus on sperm function. Mol Cell Biochem 477, 2567–2579 (2022). https://doi.org/10.1007/s11010-022-04469-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-022-04469-2

Keywords

Search

Navigation