Kappa- opioid receptor regulates human sperm functions via SPANX-A/D protein family

Itziar Urizar-Arenaza*, Nerea Osinalde, Vyacheslav Akimov, Michele Puglia, Iraia Muñoa-Hoyos, Belén Gómez-Giménez, Marta Gianzo, Teresa Ganzabal, Blagoy Blagoev, Irina Kratchmarova, Nerea Subiran

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review


The kappa-opioid receptor (KOR) is involved in the regulation of the fertilizing capacity of human sperm. Recently, a testicular-specific protein family, SPANX-A/D, has also been found to be involved in regulating this process. In order to determine if KOR has a role in the regulation of sperm fertility through the SPANX-A/D protein family, we activated the kappa opioid receptor adding its selective agonist, U50488H to normozoospermic human spermatozoa. Then, we performed immunofluorescence assays and immunoprecipitation experiments followed by LC-MS/MS. According to our results, KOR activation may cause the translocation of SPANX-A/D into the nucleus of human spermatozoa. Phosphoproteomic studies show that KOR does not cause phosphorylation changes in SPANX-A/D residues. However, interactome assays demonstrate that KOR activation provokes changes in SPANX-A/D potential interactors involved in sperm motility, energy metabolism and nuclear processes. Taking these results into account, KOR may regulate human sperm fertility through SPANX-A/D protein family, modifying its subcellular location and interactions. Although further studies are needed, this finding could help us describing the molecular mechanisms underlying sperm fertility as well as developing new strategies for treating infertility.

Original languageEnglish
JournalReproductive Biology
Issue number3
Pages (from-to)300-306
Publication statusPublished - Sep 2020


  • Kappa-opioid receptor
  • SPANX-A/D protein family
  • Sperm fertility


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