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Anandamide modulates human sperm motility: implications for men with asthenozoospermia and oligoasthenoteratozoospermia.
Hum Reprod. 2013 Aug; 28(8):2058-66.HR

Abstract

STUDY QUESTION

What are the levels of anandamide (N-arachidonoylethanolamide, AEA) in human seminal plasma and how are these related to abnormal spermatozoa?

SUMMARY ANSWER

Seminal plasma AEA levels were lower in men with asthenozoospermia and oligoasthenoteratozoospermia compared with normozoospermic men.

WHAT IS KNOWN ALREADY

AEA, a bioactive lipid, synthesized from membrane phospholipids may signal through cannabinoid receptors (CB1 and CB2) to regulate human sperm functions and male reproduction by modulating sperm motility, capacitation and the acrosome reaction in vitro. Local AEA levels are regulated by the synthetic and degradative enzymes, NAPE-PLD and FAAH, respectively. How the deregulation of this endogenous signalling pathway affects human sperm function(s) is not clear.

STUDY DESIGN, SIZE AND DURATION

This was a cross-sectional study of 86 men presenting at an infertility clinic for semen analysis over a period of 2 years.

PARTICIPANTS/MATERIALS, SETTING, METHODS

AEA was quantified, by ultra-high performance liquid chromatography-tandem mass spectrometry, in seminal plasma from 86 volunteers. Using qRT-PCR, CB1, CB2, NAPE-PLD and FAAH transcript levels were determined in spermatozoa from men with normozoospermia, asthenozoospermia, oligoasthenoteratozoospermia and teratozoospermia. Normal spermatozoa were exposed in vitro to methanadamide (meth-AEA) to determine its effect on sperm motility, viability and mitochondrial activity.

MAIN RESULTS AND THE ROLE OF CHANCE

Seminal plasma AEA levels (mean ± SEM) were significantly lower in men with asthenozoospermia (0.080 ± 0.01 nM; P < 0.05) or oligoasthenoteratozoospermia (0.083 ± 0.01 nM; P < 0.05) compared with normozoospermic men (0.198 ± 0.03 nM). In addition, the levels of spermatozoal CB1 mRNA were significantly decreased in men with asthenozoospermia (P < 0.001) or oligoasthenoteratozoospermia (P < 0.001) compared with normozoospermic controls. Supra-physiological levels of meth-AEA decreased sperm motility and viability, probably through CB1-mediated inhibition of mitochondrial activity.

LIMITATIONS, REASONS FOR CAUTION

The inhibitory effect of meth-AEA was only shown in vitro and may not reflect what happens in vivo.

WIDER IMPLICATIONS OF THE FINDINGS

As the regulation of the endocannabinoid system appears to be necessary for the preservation of normal sperm function and male fertility, there may be implications for the adverse reproductive consequences of marijuana use. Exocannabinoids, such as Δ(9)-THC, are likely to compete with endocannabinoids at the cannabinoid receptors, upsetting the finely balanced endocannabinoid signalling system. The importance of the endocannabinoid system makes it an attractive target for pharmacological interventions to control male fertility.

STUDY FUNDING/COMPETING INTEREST(S)

This work was funded in part by miscellaneous educational funds from the University Hospitals of Leicester National Health Services Trust to support the Endocannabinoid Research Laboratory of University of Leicester. The authors declare no competing interests.

Authors+Show Affiliations

Endocannabinoid Research Group, Reproductive Science Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester LE2 7LX, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23697839

Citation

Amoako, A A., et al. "Anandamide Modulates Human Sperm Motility: Implications for Men With Asthenozoospermia and Oligoasthenoteratozoospermia." Human Reproduction (Oxford, England), vol. 28, no. 8, 2013, pp. 2058-66.
Amoako AA, Marczylo TH, Marczylo EL, et al. Anandamide modulates human sperm motility: implications for men with asthenozoospermia and oligoasthenoteratozoospermia. Hum Reprod. 2013;28(8):2058-66.
Amoako, A. A., Marczylo, T. H., Marczylo, E. L., Elson, J., Willets, J. M., Taylor, A. H., & Konje, J. C. (2013). Anandamide modulates human sperm motility: implications for men with asthenozoospermia and oligoasthenoteratozoospermia. Human Reproduction (Oxford, England), 28(8), 2058-66. https://doi.org/10.1093/humrep/det232
Amoako AA, et al. Anandamide Modulates Human Sperm Motility: Implications for Men With Asthenozoospermia and Oligoasthenoteratozoospermia. Hum Reprod. 2013;28(8):2058-66. PubMed PMID: 23697839.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anandamide modulates human sperm motility: implications for men with asthenozoospermia and oligoasthenoteratozoospermia. AU - Amoako,A A, AU - Marczylo,T H, AU - Marczylo,E L, AU - Elson,J, AU - Willets,J M, AU - Taylor,A H, AU - Konje,J C, Y1 - 2013/05/21/ PY - 2013/5/24/entrez PY - 2013/5/24/pubmed PY - 2014/3/4/medline KW - anandamide KW - endocannabinoid system KW - male infertility KW - seminal plasma KW - spermatozoa SP - 2058 EP - 66 JF - Human reproduction (Oxford, England) JO - Hum Reprod VL - 28 IS - 8 N2 - STUDY QUESTION: What are the levels of anandamide (N-arachidonoylethanolamide, AEA) in human seminal plasma and how are these related to abnormal spermatozoa? SUMMARY ANSWER: Seminal plasma AEA levels were lower in men with asthenozoospermia and oligoasthenoteratozoospermia compared with normozoospermic men. WHAT IS KNOWN ALREADY: AEA, a bioactive lipid, synthesized from membrane phospholipids may signal through cannabinoid receptors (CB1 and CB2) to regulate human sperm functions and male reproduction by modulating sperm motility, capacitation and the acrosome reaction in vitro. Local AEA levels are regulated by the synthetic and degradative enzymes, NAPE-PLD and FAAH, respectively. How the deregulation of this endogenous signalling pathway affects human sperm function(s) is not clear. STUDY DESIGN, SIZE AND DURATION: This was a cross-sectional study of 86 men presenting at an infertility clinic for semen analysis over a period of 2 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: AEA was quantified, by ultra-high performance liquid chromatography-tandem mass spectrometry, in seminal plasma from 86 volunteers. Using qRT-PCR, CB1, CB2, NAPE-PLD and FAAH transcript levels were determined in spermatozoa from men with normozoospermia, asthenozoospermia, oligoasthenoteratozoospermia and teratozoospermia. Normal spermatozoa were exposed in vitro to methanadamide (meth-AEA) to determine its effect on sperm motility, viability and mitochondrial activity. MAIN RESULTS AND THE ROLE OF CHANCE: Seminal plasma AEA levels (mean ± SEM) were significantly lower in men with asthenozoospermia (0.080 ± 0.01 nM; P < 0.05) or oligoasthenoteratozoospermia (0.083 ± 0.01 nM; P < 0.05) compared with normozoospermic men (0.198 ± 0.03 nM). In addition, the levels of spermatozoal CB1 mRNA were significantly decreased in men with asthenozoospermia (P < 0.001) or oligoasthenoteratozoospermia (P < 0.001) compared with normozoospermic controls. Supra-physiological levels of meth-AEA decreased sperm motility and viability, probably through CB1-mediated inhibition of mitochondrial activity. LIMITATIONS, REASONS FOR CAUTION: The inhibitory effect of meth-AEA was only shown in vitro and may not reflect what happens in vivo. WIDER IMPLICATIONS OF THE FINDINGS: As the regulation of the endocannabinoid system appears to be necessary for the preservation of normal sperm function and male fertility, there may be implications for the adverse reproductive consequences of marijuana use. Exocannabinoids, such as Δ(9)-THC, are likely to compete with endocannabinoids at the cannabinoid receptors, upsetting the finely balanced endocannabinoid signalling system. The importance of the endocannabinoid system makes it an attractive target for pharmacological interventions to control male fertility. STUDY FUNDING/COMPETING INTEREST(S): This work was funded in part by miscellaneous educational funds from the University Hospitals of Leicester National Health Services Trust to support the Endocannabinoid Research Laboratory of University of Leicester. The authors declare no competing interests. SN - 1460-2350 UR - https://www.unboundmedicine.com/medline/citation/23697839/Anandamide_modulates_human_sperm_motility:_implications_for_men_with_asthenozoospermia_and_oligoasthenoteratozoospermia_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/det232 DB - PRIME DP - Unbound Medicine ER -