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Cannabis et fertilité masculine

Cannabis and male fertility

Basic and Clinical Andrology volume 20, pages 123–130 (2010)Cite this article

Résumé

Le cannabis est la drogue récréative la plus utilisée dans le monde. Une des inquiétudes majeures de l’exposition au cannabis concerne son effet négatif sur la fonction reproductive. La découverte du système endocannabinnoïde, composé de multiples ligands endogènes lipidiques, leurs récepteurs et leurs enzymes métaboliques, a permis de mettre en évidence l’importance de la signalisation de ce système dans de multiples événements de la reproduction. Dans cet article, nous nous proposons de passer en revue la littérature sur l’impact du cannabis dans la fonction reproductive masculine. Nous aborderons les études réalisées chez l’homme et chez l’animal, et enfin nous discuterons les limites et perspectives des études envisageables pour évaluer les effets du cannabis sur la fertilité masculine.

Abstract

Cannabis is the most used recreational drug in the world. One of the major concerns of exposure to the cannabis is its negative effect on the reproductive function. The discovery of the endocannabinoid system, composed of multiple endogenous lipid ligands, their receptors and their metabolic enzymes, highlights the importance of the signaling pathways of this system in multiple events of reproduction. The objective of this study is to review the impact of the cannabis on male reproductive function. The limits and the perspective possible studies to evaluate the effects of the cannabis on male fertility are discussed in this study on the basis of the studies carried out on men and animals.

Références

  1. Park B, McPartland JM, Glass M (2004) Cannabis, cannabinoids and reproduction. Prostaglandins Leukot Essent Fatty Acids 70:189–97

    Article  PubMed  CAS  Google Scholar 

  2. Davitian C, Uzan M, Tigaizin A, et al (2006) Consommation maternelle de cannabis et retard de croissance intra-utérin. Gynecol Obstet Fertil 34:632–7

    Article  PubMed  CAS  Google Scholar 

  3. Zajicek J, Fox P, Sanders H, et al (2003) Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet 362:1517–26

    Article  PubMed  CAS  Google Scholar 

  4. Gaoni Y, Mechoulam R (1971) The isolation and structure of delta-1-tetrahydrocannabinol and other neutral cannabinoids from hashish. J Am Chem Soc 93:217–24

    Article  PubMed  CAS  Google Scholar 

  5. Hirst RA, Lambert DG, Notcutt WG (1998) Pharmacology and potential therapeutic uses of cannabis. Br J Anaesth 81:77–84

    Article  PubMed  CAS  Google Scholar 

  6. Matsuda LA, Lolait SJ, Brownstein MJ, et al (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–4

    Article  PubMed  CAS  Google Scholar 

  7. Munro S, Thomas KL, Abu-Shaar M (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61–5

    Article  PubMed  CAS  Google Scholar 

  8. McAllister SD, Glass M (2002) CB(1) and CB(2) receptormediated signalling: a focus on endocannabinoids. Prostaglandins Leukot Essent Fatty Acids 66:161–71

    Article  PubMed  CAS  Google Scholar 

  9. Herkenham M, Lynn AB, Little MD, et al (1990) Cannabinoid receptor localization in brain. Proc Natl Acad Sci USA 87:1932–6

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  10. Glass M, Dragunow M, Faull RL (1997) Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience 77:299–318

    Article  PubMed  CAS  Google Scholar 

  11. McPartland JM, Pruitt PL (1999) Side effects of pharmaceuticals not elicited by comparable herbal medicines: the case of tetrahydrocannabinol and marijuana. Altern Ther Health Med 5:57–62

    PubMed  CAS  Google Scholar 

  12. 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 105:2699–704

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Maccarrone M (2009) Endocannabinoids: friends and foes of reproduction. Prog Lipid Res 48:344–54

    Article  PubMed  CAS  Google Scholar 

  14. Devane WA, Hanus L, Breuer A, et al (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:1946–9

    Article  PubMed  CAS  Google Scholar 

  15. Mechoulam R, Ben-Shabat S, Hanus L, et al (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 50:83–90

    Article  PubMed  CAS  Google Scholar 

  16. Hanus L, Abu-Lafi S, Fride E, et al (2001) 2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor. Proc Natl Acad Sci USA 98:3662–5

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  17. Porter AC, Sauer JM, Knierman MD, et al (2002) Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. J Pharmacol Exp Ther 301:1020–4

    Article  PubMed  CAS  Google Scholar 

  18. Schuel H, Burkman LJ, Lippes J, et al (2002) N-Acylethanolamines in human reproductive fluids. Chem Phys Lipids 121:211–27

    Article  PubMed  CAS  Google Scholar 

  19. Maccarrone M (2009) Endocannabinoids and reproductive endocrinology. Curr Opin Investig Drugs 10:305–10

    PubMed  CAS  Google Scholar 

  20. Di Marzo V (2008) Targeting the endocannabinoid system: to enhance or reduce? Nat Rev Drug Discov 7:438–55

    Article  PubMed  Google Scholar 

  21. Lynskey M, Hall W (2000) The effects of adolescent cannabis use on educational attainment: a review. Addiction 95:1621–30

    Article  PubMed  CAS  Google Scholar 

  22. Sugiura T, Kobayashi Y, Oka S, Waku K (2002) Biosynthesis and degradation of anandamide and 2-arachidonoylglycerol and their possible physiological significance. Prostaglandins Leukot Essent Fatty Acids 66:173–92

    Article  PubMed  CAS  Google Scholar 

  23. Fride E (2002) Endocannabinoids in the central nervous system-an overview. Prostaglandins Leukot Essent Fatty Acids 66:221–33

    Article  PubMed  CAS  Google Scholar 

  24. Di Marzo V, Fontana A, Cadas H, et al (1994) Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 372:686–91

    Article  PubMed  Google Scholar 

  25. Kozak KR, Rowlinson SW, Marnett LJ (2000) Oxygenation of the endocannabinoid, 2-arachidonylglycerol, to glyceryl prostaglandins by cyclooxygenase-2. J Biol Chem 275:33744–9

    Article  PubMed  CAS  Google Scholar 

  26. Bornheim LM, Kim KY, Chen B, Correia MA (1995) Microsomal cytochrome P450-mediated liver and brain anandamide metabolism. Biochem Pharmacol 50:677–86

    Article  PubMed  CAS  Google Scholar 

  27. Battista N, Pasquariello N, Di Tommaso M, Maccarrone M (2008) Interplay between endocannabinoids, steroids and cytokines in the control of human reproduction. J Neuroendocrinol 20 Suppl 1:82–9

    Google Scholar 

  28. Lewis SE, Maccarrone M (2009) Endocannabinoids, sperm biology and human fertility. Pharmacol Res 60:126–31

    Article  PubMed  CAS  Google Scholar 

  29. Wenger T, Toth BE, Juaneda C, et al (1999) The effects of cannabinoids on the regulation of reproduction. Life Sci 65:695–701

    Article  PubMed  CAS  Google Scholar 

  30. Agirregoitia E, Carracedo A, Subiran N, et al (2009) The CB(2) cannabinoid receptor regulates human sperm cell motility. Fertil Steril

  31. Walker WH, Cheng J (2005) FSH and testosterone signaling in Sertoli cells. Reproduction 130:15–28

    Article  PubMed  CAS  Google Scholar 

  32. Pentikainen V, Erkkila K, Suomalainen L, et al (2000) Estradiol acts as a germ cell survival factor in the human testis in vitro. J Clin Endocrinol Metab 85:2057–67

    PubMed  CAS  Google Scholar 

  33. McDonald CA, Millena AC, Reddy S, et al (2006) Follicle-stimulating hormone-induced aromatase in immature rat Sertoli cells requires an active phosphatidylinositol 3-kinase pathway and is inhibited via the mitogen-activated protein kinase signaling pathway. Mol Endocrinol 20:608–18

    Article  PubMed  CAS  Google Scholar 

  34. Maccarrone M, Cecconi S, Rossi G, et al (2003) Anandamide activity and degradation are regulated by early postnatal aging and follicle-stimulating hormone in mouse Sertoli cells. Endocrinology 144:20–8

    Article  PubMed  CAS  Google Scholar 

  35. Rossi G, Gasperi V, Paro R, et al (2007) Follicle-stimulating hormone activates fatty acid amide hydrolase by protein kinase A and aromatase-dependent pathways in mouse primary Sertoli cells. Endocrinology 148:1431–9

    Article  PubMed  CAS  Google Scholar 

  36. Puffenbarger RA (2005) Molecular biology of the enzymes that degrade endocannabinoids. Curr Drug Targets CNS Neurol Disord 4:625–31

    Article  PubMed  CAS  Google Scholar 

  37. Chang MC, Berkery D, Schuel R, et al (1993) Evidence for a cannabinoid receptor in sea urchin sperm and its role in blockade of the acrosome reaction. Mol Reprod Dev 36:507–16

    Article  PubMed  CAS  Google Scholar 

  38. 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 118:4393–404

    Article  PubMed  CAS  Google Scholar 

  39. Rossato M, Ion Popa F, Ferigo M, et al (2005) Human sperm express cannabinoid receptor Cb1, the activation of which inhibits motility, acrosome reaction and mitochondrial function. J Clin Endocrinol Metab 90:984–91

    Article  PubMed  CAS  Google Scholar 

  40. Ricci G, Cacciola G, Altucci L, et al (2007) Endocannabinoid control of sperm motility: the role of epididymus. Gen Comp Endocrinol 153:320–2

    Article  PubMed  CAS  Google Scholar 

  41. O’Connell M, McClure N, Powell LA, et al (2003) Differences in mitochondrial and nuclear DNA status of high-density and lowdensity sperm fractions after density centrifugation preparation. Fertil Steril 79 Suppl 1:754–62

    Google Scholar 

  42. Sarafian TA, Kouyoumjian S, Khoshaghideh F, et al (2003) Delta-9-tetrahydrocannabinol disrupts mitochondrial function and cell energetics. Am J Physiol Lung Cell Mol Physiol 284: L298–L306

    Article  PubMed  CAS  Google Scholar 

  43. Gervasi MG, Rapanelli M, Ribeiro ML, et al (2009) The endocannabinoid system in bull sperm and bovine oviductal epithelium: role of anandamide in sperm-oviduct interaction. Reproduction 137:403–14

    Article  PubMed  CAS  Google Scholar 

  44. Sun X, Wang H, Okabe M, et al (2009) Genetic loss of Faah compromises male fertility in mice. Biol Reprod 80:235–42

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  45. Wang H, Dey SK, Maccarrone M (2006) Jekyll and Hyde: two faces of cannabinoid signaling in male and female fertility. Endocr Rev 27:427–48

    Article  PubMed  CAS  Google Scholar 

  46. Kolodny RC, Masters WH, Kolodner RM, Toro G (1974) Depression of plasma testosterone levels after chronic intensive marihuana use. N Engl J Med 290:872–4

    Article  PubMed  CAS  Google Scholar 

  47. Hembree WC, 3rd, Nahas GG, Zeidenberg P, Huang HF (1978) Changes in human spermatozoa associated with high dose marihuana smoking. Adv Biosci 22-3:429–39

    Google Scholar 

  48. Mendelson JH, Kuehnle J, Ellingboe J, Babor TF (1974) Plasma testosterone levels before, during and after chronic marihuana smoking. N Engl J Med 291:1051–5

    Article  PubMed  CAS  Google Scholar 

  49. Whan LB, West MC, McClure N, Lewis SE (2006) Effects of delta-9-tetrahydrocannabinol, the primary psychoactive cannabinoid in marijuana, on human sperm function in vitro. Fertil Steril 85:653–60

    Article  PubMed  CAS  Google Scholar 

  50. Wenger T, Rettori V, Snyder GD, et al (1987) Effects of delta-9-tetrahydrocannabinol on the hypothalamic-pituitary control of luteinizing hormone and follicle-stimulating hormone secretion in adult male rats. Neuroendocrinology 46:488–93

    Article  PubMed  CAS  Google Scholar 

  51. Ayalon D, Nir I, Cordova T, et al (1977) Acute effect of delta1-tetrahydrocannabinol on the hypothalamo-pituitary-ovarian axis in the rat. Neuroendocrinology 23:31–42

    Article  PubMed  CAS  Google Scholar 

  52. Besch NF, Smith CG, Besch PK, Kaufman RH (1977) The effect of marihuana (delta-9-tetrahydrocannabinol) on the secretion of luteinizing hormone in the ovariectomized rhesus monkey. Am J Obstet Gynecol 128:635–42

    PubMed  CAS  Google Scholar 

  53. Smith CG, Besch NF, Smith RG, Besch PK (1979) Effect of tetrahydrocannabinol on the hypothalamic-pituitary axis in the ovariectomized rhesus monkey. Fertil Steril 31:335–9

    PubMed  CAS  Google Scholar 

  54. List A, Nazar B, Nyquist S, Harclerode J (1977) The effects of delta-9-tetrahydrocannabinol and cannabidiol on the metabolism of gonadal steroids in the rat. Drug Metab Dispos 5:268–72

    PubMed  CAS  Google Scholar 

  55. Harclerode J, Nyquist SE, Nazar B, Lowe D (1978) Effects of cannabis on sex hormones and testicular enzymes of the rodent. Adv Biosci 22-3:395–405

    Google Scholar 

  56. Jakubovic A, McGeer EG, McGeer PL (1979) Effects of cannabinoids on testosterone and protein synthesis in rat testis Leydig cells in vitro. Mol Cell Endocrinol 15:41–50

    Article  PubMed  CAS  Google Scholar 

  57. Husain S, Lame M, De Boer B (1979) Rat testicular tissue glucose metabolism in the presence of delta-9-tetrahydrocannabinol. Proc West Pharmacol Soc 22:355–8

    PubMed  CAS  Google Scholar 

  58. Merari A, Barak A, Plaves M (1973) Effects of 1(2) -tetrahydrocannabinolon copulation in the male rat. Psychopharmacologia 28:243–6

    Article  PubMed  CAS  Google Scholar 

  59. Corcoran ME, Amit Z, Malsbury CW, Daykin S (1974) Reduction in copulatory behavior of male rats following hashish injections. Res Commun Chem Pathol Pharmacol 7:779–82

    PubMed  CAS  Google Scholar 

  60. Schuel H, Chang MC, Berkery D, et al (1991) Cannabinoids inhibit fertilization in sea urchins by reducing the fertilizing capacity of sperm. Pharmacol Biochem Behav 40:609–15

    Article  PubMed  CAS  Google Scholar 

  61. Zimmerman AM, Zimmerman S, Raj AY (1978) Effects of cannabinoids on spermatogenesis in mice. Adv Biosci 22-3:407–18

    Google Scholar 

  62. Perez LE, Smith CG, Asch RH (1981) delta-9-tetrahydrocannabinol inhibits fructose utilization and motility in human, rhesus monkey and rabbit sperm in vitro. Fertil Steril 35:703–5

    PubMed  CAS  Google Scholar 

  63. Shahar A, Bino T (1974) In vitro effects of delta-9-tetrahydrocannabinol (THC) on bull sperm. Biochem Pharmacol 23:1341–2

    Article  PubMed  CAS  Google Scholar 

  64. WHO (1999) WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. Cambridge University Press, Cambridge (UK)

    Google Scholar 

  65. Donnelly ET, Lewis SE, McNally JA, Thompson W(1998) In vitro fertilization and pregnancy rates: the influence of sperm motility and morphology on IVF outcome. Fertil Steril 70:305–14

    Article  PubMed  CAS  Google Scholar 

  66. Cordier S (1995) Environnement et santé une relation difficile à étudier. Actualité et dossier en santé publique 13:3–6

    Google Scholar 

  67. Perry MJ (2008) Effects of environmental and occupational pesticide exposure on human sperm: a systematic review. Hum Reprod Update 14:233–42

    Article  PubMed  CAS  Google Scholar 

  68. Grotenhermen F (2003) Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet 42:327–60

    Article  PubMed  CAS  Google Scholar 

  69. Mura P (2000) La recherche et le dosage des cannabinoïdes pourquoi et comment ? Rev Fr Lab 322:31–3

    Google Scholar 

  70. Battista N, Rapino C, Di Tommaso M, et al (2008) Regulation of male fertility by the endocannabinoid system. Mol Cell Endocrinol 286:S17–S23

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Laboratoire de biochimie-hormonologie, CHU de Pointe-à-Pitre, BP 465, F-97159, Pointe-à-Pitre cedex, Guadeloupe

    Y. Alj, M. Demonlis & J. Bangou

  2. Centre caribéen de médecine de la reproduction, CHU de Pointe-à-Pitre, F-97159, Pointe-à-Pitre cedex, Guadeloupe

    L. Pavili, X. Dellis & G. Joguet

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  1. Y. Alj
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  2. M. Demonlis
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Correspondence to Y. Alj.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Alj, Y., Demonlis, M., Pavili, L. et al. Cannabis et fertilité masculine. Basic Clin. Androl. 20, 123–130 (2010). https://doi.org/10.1007/s12610-010-0075-2

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Basic and Clinical Andrology

ISSN: 2051-4190