Evidence that anandamide-signaling regulates human sperm functions required for fertilization

Herbert Schuel, Lani J. Burkman, Jack Lippes, Kent Crickard, Mary C. Mahony, Andrea Giuffrida, Robert P. Picone, Alexandros Makriyannis

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Ejaculated mammalian sperm require several hours exposure to secretions in female reproductive tracts, or incubation in appropriate culture medium in vitro, before acquiring the capacity to fertilize eggs. Arachidonylethanolamide (AEA), also known as anandamide, is a novel lipid-signal molecule that is an endogenous agonist (endocannabinoid) for cannabinoid receptors. We now report that AEA is present in human seminal plasma, mid-cycle oviductal fluid, and follicular fluid analyzed by high-performance liquid chromatography/mass spectrometry. Sperm are sequentially exposed to these reproductive fluids as they move from the vagina to the site of fertilization in the oviduct. Specific binding of the potent cannabinoid agonist [3H]CP-55,940 to human sperm was saturable (KD 9.71 ± 1.04 nM), suggesting that they express cannabinoid receptors. R-methanandamide [AM-356], a potent and metabolically stable AEA analog, and (-)Δ9 tetrahydrocannabinol (THC), the major psychoactive constituent of Cannabis, modulated capacitation and fertilizing potential of human sperm in vitro. AM-356 elicited biphasic effects on the incidence of hyperactivated sperm motility (HA) between 1 and 6 hr of incubation: at (2.5 nM) it inhibited HA, while at (0.25 nM) it stimulated HA. Both AM-356 and THC inhibited morphological alterations over acrosomal caps between 2 and 6 hr (IC50 5.9 ± 0.6 pM and 3.5 ± 1.5 nM, respectively). Sperm fertilizing capacity, measured in the Hemizona Assay, was reduced 50% by (1 nM) AM-356. These findings suggest that AEA-signaling may regulate sperm functions required for fertilization in human reproductive tracts, and imply that smoking of marijuana could impact these processes. This study has potential medical and public policy ramifications because of the incidence of marijuana abuse by adults in our society, previously documented reproductive effects of marijuana, and the ongoing debate about medicinal use of marijuana and cannabinoids.

Original languageEnglish (US)
Pages (from-to)376-387
Number of pages12
JournalMolecular Reproduction and Development
Volume63
Issue number3
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

Fingerprint

Fertilization
Spermatozoa
Cannabinoid Receptor Agonists
Dronabinol
Cannabis
Medical Marijuana
Marijuana Smoking
Marijuana Abuse
Cannabinoid Receptors
Follicular Fluid
Endocannabinoids
Oviducts
Cannabinoids
Sperm Motility
Incidence
Vagina
Public Policy
Semen
Eggs
Inhibitory Concentration 50

Keywords

  • Cannabinoid receptor
  • Eicosanoid
  • Endocannabinoid
  • Fertilization
  • Follicular fluid
  • N-acylethanolamides
  • Oviductal fluid
  • Seminal plasma
  • Sperm capacitation

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

Evidence that anandamide-signaling regulates human sperm functions required for fertilization. / Schuel, Herbert; Burkman, Lani J.; Lippes, Jack; Crickard, Kent; Mahony, Mary C.; Giuffrida, Andrea; Picone, Robert P.; Makriyannis, Alexandros.

In: Molecular Reproduction and Development, Vol. 63, No. 3, 01.11.2002, p. 376-387.

Research output: Contribution to journalArticle

Schuel, H, Burkman, LJ, Lippes, J, Crickard, K, Mahony, MC, Giuffrida, A, Picone, RP & Makriyannis, A 2002, 'Evidence that anandamide-signaling regulates human sperm functions required for fertilization', Molecular Reproduction and Development, vol. 63, no. 3, pp. 376-387. https://doi.org/10.1002/mrd.90021
Schuel, Herbert ; Burkman, Lani J. ; Lippes, Jack ; Crickard, Kent ; Mahony, Mary C. ; Giuffrida, Andrea ; Picone, Robert P. ; Makriyannis, Alexandros. / Evidence that anandamide-signaling regulates human sperm functions required for fertilization. In: Molecular Reproduction and Development. 2002 ; Vol. 63, No. 3. pp. 376-387.
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