Inhibition of sperm motility in male macaques with EP055, a potential non-hormonal male contraceptive

Michael G. O’Rand, Katherine G. Hamil, Tiffany Adevai, Mary Zelinski

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    Men have two practical choices for contraception; the condom which has a high typical use failure rate or vasectomy. New male hormonal and non-hormonal contraceptives are under development that target either the production of sperm (spermatogenesis) or the delivery of sperm. One particular target is the sperm protein EPPIN, which is present on the surface of human spermatozoa. EP055 is a small organic compound that targets EPPIN on the surface of sperm and inhibits motility. EP055 was tested in cynomolgus (Macaca fascicularis) males to determine its plasma half-life after intravenous (i.v.) infusion of a single dose and for binding to its target tissues. Our initial study demonstrated a plasma half-life for EP055 of 10.6 minutes. In a second study examination of macaque testis, epididymis, and plasma after i.v. infusion of a single dose of compound EP055 (63.25 mg/kg) demonstrated that EP055 was detected in testis and epididymis two hours and six hours post-infusion. We initiated a trial in rhesus (Macaca mulatta) males to assess the availability of EP055 in semen and its effect on sperm motility as a measure of the drug’s efficacy. Four macaques were infused with a low dose (75–80 mg/kg) followed by a recovery period and a subsequent high dose (125–130 mg/kg) of EP055. After high dose administration, sperm motility fell to approximately 20% of pretreatment levels within 6 hours post-infusion; no normal motility was observed at 30 hours post-infusion. Recovery of sperm motility was obvious by 78 hours post-infusion; with full recovery in all animals by 18 days post-infusion. EP055 has the potential to be a male contraceptive that would provide a reversible, short-lived pharmacological alternative.

    Original languageEnglish (US)
    Article numbere0195953
    JournalPLoS One
    Volume13
    Issue number4
    DOIs
    StatePublished - Apr 1 2018

    Fingerprint

    Male Contraceptive Agents
    contraceptives
    Sperm Motility
    Macaca
    sperm motility
    Spermatozoa
    spermatozoa
    Plasmas
    Recovery
    Epididymis
    dosage
    Intravenous Infusions
    epididymis
    Half-Life
    Testis
    half life
    Contraceptive Agents
    testes
    Organic compounds
    Vasectomy

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)

    Cite this

    Inhibition of sperm motility in male macaques with EP055, a potential non-hormonal male contraceptive. / O’Rand, Michael G.; Hamil, Katherine G.; Adevai, Tiffany; Zelinski, Mary.

    In: PLoS One, Vol. 13, No. 4, e0195953, 01.04.2018.

    Research output: Contribution to journalArticle

    O’Rand, Michael G. ; Hamil, Katherine G. ; Adevai, Tiffany ; Zelinski, Mary. / Inhibition of sperm motility in male macaques with EP055, a potential non-hormonal male contraceptive. In: PLoS One. 2018 ; Vol. 13, No. 4.
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    abstract = "Men have two practical choices for contraception; the condom which has a high typical use failure rate or vasectomy. New male hormonal and non-hormonal contraceptives are under development that target either the production of sperm (spermatogenesis) or the delivery of sperm. One particular target is the sperm protein EPPIN, which is present on the surface of human spermatozoa. EP055 is a small organic compound that targets EPPIN on the surface of sperm and inhibits motility. EP055 was tested in cynomolgus (Macaca fascicularis) males to determine its plasma half-life after intravenous (i.v.) infusion of a single dose and for binding to its target tissues. Our initial study demonstrated a plasma half-life for EP055 of 10.6 minutes. In a second study examination of macaque testis, epididymis, and plasma after i.v. infusion of a single dose of compound EP055 (63.25 mg/kg) demonstrated that EP055 was detected in testis and epididymis two hours and six hours post-infusion. We initiated a trial in rhesus (Macaca mulatta) males to assess the availability of EP055 in semen and its effect on sperm motility as a measure of the drug’s efficacy. Four macaques were infused with a low dose (75–80 mg/kg) followed by a recovery period and a subsequent high dose (125–130 mg/kg) of EP055. After high dose administration, sperm motility fell to approximately 20{\%} of pretreatment levels within 6 hours post-infusion; no normal motility was observed at 30 hours post-infusion. Recovery of sperm motility was obvious by 78 hours post-infusion; with full recovery in all animals by 18 days post-infusion. EP055 has the potential to be a male contraceptive that would provide a reversible, short-lived pharmacological alternative.",
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