Autocrine regulation of human sperm motility by the met-enkephalin opioid peptide

A novel role of the opioid system in the regulation of sperm function is demonstrated that shows that both exogenous and endogenous met-enkephalin can modulate sperm motility.

Nerea Subirán, Ph.D., Luz Candenas, Ph.D., Francisco M. Pinto, Ph.D., Ekaitz Agirregoitia,
Ph.D., Antonio Cejudo-Román, J.D., Jon Irazusta, Ph.D.

Volume 98, Issue 3, Pages 617-625.e3, September 2012


To verify the presence of protein precursor pro-enkephalin (PENK) and metenkephalin in human spermatozoa and to characterize the effects of exogenous and endogenous enkephalins on sperm motility.

We carried out expression assays for met-enkephalin and its protein precursor PENK by RTPCR, Western blot and immunofluorescence techniques in sperm cells and motility analysis after incubation of semen samples with met-enkephlin enzyme inhibitors and the opioid receptor antagonist naloxone. Met-enkephalin secretion was analyzed by flow cytometry.

Assisted reproduction unit and academic research laboratory.

Semen from 50 normozoospermic healthy human donors.

Spermatozoa isolated from semen on discontinuous Percoll gradient (40%-80%) followed by a swim-up were used for all techniques.

Main Outcome Measure(s):
Immunoblotting blots, indirect immunofluorescence antibody assays, RTPCR blots, flow cytometry plots, and percentage of motile sperm.

We found by RT-PCR and immunofluorescence that met-enkephalin and its protein precursor PENK are present in the head of human sperm cells. Endogenous met-enkephalin increased sperm motility, whereas the addition of exogenous met-enkephalin had a biphasic effect on motility, likely due to the activation of distinct receptor subtypes.

We provide evidence for a new role of met-enkephalin as an endogenous mediator of sperm motility. This autocrine regulation of sperm function by the opioid system represents a new mechanism of regulation of male fertility and could be useful as an emerging target for male contraception.

  • NicoGarrido

    I would like to congratulate the authors for their nice work, addressing the regulation of sperm motility in an elegant way.
    The authors manily dedicated the discussion and conclusions regarding the contraceptive aspects of these findings.
    From my viewpoint, given that I work in an assisted reproduction unit, and then, our main objective is bringing babies at home, the interpretation of the findings I do is the opposite.
    Among their findings they stated ” incubation with met-enkephalin for 3 hours was found to increase sperm motility in a dose-independent manner. This result is consistent with previous reports that met-enkephalin maintains sperm motility at long times”
    This could open new possibilities in the sperm handling medium composition, for instance in order to enhance sperm motility in samples dedicated to assisted reproduction procedures, aiming to improve the results.
    What do the authors think about this?
    Thanks a lot!

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