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Updated: May 20, 2026

Measuring Sperm Guidance and Motility within the Caenorhabditis elegans Hermaphrodite Reproductive Tract
Published on: June 6, 2019
Autocrine regulation of human sperm motility by the met-enkephalin opioid peptide
Nerea Subirán1, Luz Candenas, Francisco M Pinto
1Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country, Leioa, Bizkaia. nerea.subiran@ehu
Objective:
To verify the presence of protein precursor pro-enkephalin (PENK) and met-enkephalin in human spermatozoa and to characterize the effects of exogenous and endogenous enkephalins on sperm motility.
Design:
We carried out expression assays for met-enkephalin and its protein precursor PENK by reverse transcription-polymerase chain reaction (RT-PCR), 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.
Setting:
Assisted reproduction unit and academic research laboratory.
Patient(S):
Semen from 50 normozoospermic healthy human donors.
Intervention(S):
Spermatozoa isolated from semen on discontinuous Percoll gradient (40%-80%) followed by a swim-up was used for all techniques.
Main Outcome Measure(S):
Immunoblotting blots, indirect immunofluorescence antibody assays, RT-PCR blots, flow cytometry plots, and percentage of motile sperm.
Result(S):
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.
Conclusion(S):
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 factor fertility and could be useful as an emerging target for male contraception.
Insights
Met-enkephalin and its precursor PENK are present in human sperm, influencing motility. This opioid system regulation offers new insights into male fertility and potential male contraception targets.
Area of Science:
- Reproductive Biology
- Molecular Endocrinology
- Sperm Physiology
Background:
- The role of endogenous peptides in sperm function is not fully understood.
- Opioid peptides, like enkephalins, are known to have diverse physiological roles.
Purpose of the Study:
- To investigate the presence of met-enkephalin and its precursor pro-enkephalin (PENK) in human spermatozoa.
- To determine the impact of endogenous and exogenous enkephalins on sperm motility.
Main Methods:
- Expression analysis using RT-PCR, Western blot, and immunofluorescence.
- Sperm motility assessment after incubation with enzyme inhibitors and naloxone.
- Met-enkephalin secretion analysis via flow cytometry.
Main Results:
- Met-enkephalin and PENK were detected in the head of human sperm cells.
- Endogenous met-enkephalin enhanced sperm motility.
- Exogenous met-enkephalin exhibited a biphasic effect on motility, suggesting receptor subtype involvement.
Conclusions:
- Met-enkephalin acts as an endogenous mediator of human sperm motility.
- This autocrine regulation by the opioid system impacts male factor fertility.
- The findings suggest potential targets for male contraception development.
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