Advances in non-hormonal male contraception targeting sperm motility

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dc.contributor.authorMariani, Noemia A. P. [UNESP]
dc.contributor.authorSilva, Joana
dc.contributor.authorFardilha, Margarida
dc.contributor.authorSilva, Erick J. R. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionUniv Aveiro
dc.contributor.institutionUniv Porto
dc.date.accessioned2023-07-29T12:00:26Z
dc.date.available2023-07-29T12:00:26Z
dc.date.issued2023-05-04
dc.description.abstractBACKGROUND The high rates of unintended pregnancy and the ever-growing world population impose health, economic, social, and environmental threats to countries. Expanding contraceptive options, including male methods, are urgently needed to tackle these global challenges. Male contraception is limited to condoms and vasectomy, which are unsuitable for many couples. Thus, novel male contraceptive methods may reduce unintended pregnancies, meet the contraceptive needs of couples, and foster gender equality in carrying the contraceptive burden. In this regard, the spermatozoon emerges as a source of druggable targets for on-demand, non-hormonal male contraception based on disrupting sperm motility or fertilization. OBJECTIVE AND RATIONALE A better understanding of the molecules governing sperm motility can lead to innovative approaches toward safe and effective male contraceptives. This review discusses cutting-edge knowledge on sperm-specific targets for male contraception, focusing on those with crucial roles in sperm motility. We also highlight challenges and opportunities in male contraceptive drug development targeting spermatozoa. SEARCH METHODS We conducted a literature search in the PubMed database using the following keywords: 'spermatozoa', 'sperm motility', 'male contraception', and 'drug targets' in combination with other related terms to the field. Publications until January 2023 written in English were considered. OUTCOMES Efforts for developing non-hormonal strategies for male contraception resulted in the identification of candidates specifically expressed or enriched in spermatozoa, including enzymes (PP1 gamma 2, GAPDHS, and sAC), ion channels (CatSper and KSper), transmembrane transporters (sNHE, SLC26A8, and ATP1A4), and surface proteins (EPPIN). These targets are usually located in the sperm flagellum. Their indispensable roles in sperm motility and male fertility were confirmed by genetic or immunological approaches using animal models and gene mutations associated with male infertility due to sperm defects in humans. Their druggability was demonstrated by the identification of drug-like small organic ligands displaying spermiostatic activity in preclinical trials. WIDER IMPLICATIONS A wide range of sperm-associated proteins has arisen as key regulators of sperm motility, providing compelling druggable candidates for male contraception. Nevertheless, no pharmacological agent has reached clinical developmental stages. One reason is the slow progress in translating the preclinical and drug discovery findings into a drug-like candidate adequate for clinical development. Thus, intense collaboration among academia, private sectors, governments, and regulatory agencies will be crucial to combine expertise for the development of male contraceptives targeting sperm function by (i) improving target structural characterization and the design of highly selective ligands, (ii) conducting long-term preclinical safety, efficacy, and reversibility evaluation, and (iii) establishing rigorous guidelines and endpoints for clinical trials and regulatory evaluation, thus allowing their testing in humans.en
dc.description.affiliationSao Paulo State Univ, Inst Biosci Botucatu, Dept Biophys & Pharmacol, BR-18618689 Botucatu, SP, Brazil
dc.description.affiliationUniv Aveiro, Inst Biomed iBiMED, Dept Med Sci, P-3810193 Aveiro, Portugal
dc.description.affiliationUniv Aveiro, QOPNA, Aveiro, Portugal
dc.description.affiliationUniv Aveiro, Dept Chem, LAQV, Aveiro, Portugal
dc.description.affiliationUniv Porto, Inst Biomed Sci Abel Salazar ICBAS, Multidisciplinary Res Biomed UMIB, Porto, Portugal
dc.description.affiliationUnespSao Paulo State Univ, Inst Biosci Botucatu, Dept Biophys & Pharmacol, BR-18618689 Botucatu, SP, Brazil
dc.format.extent25
dc.identifierhttp://dx.doi.org/10.1093/humupd/dmad008
dc.identifier.citationHuman Reproduction Update. Oxford: Oxford Univ Press, 25 p., 2023.
dc.identifier.doi10.1093/humupd/dmad008
dc.identifier.issn1355-4786
dc.identifier.urihttp://hdl.handle.net/11449/245625
dc.identifier.wosWOS:000980057900001
dc.language.isoeng
dc.publisherOxford Univ Press
dc.relation.ispartofHuman Reproduction Update
dc.sourceWeb of Science
dc.subjectspermatozoon
dc.subjection channels
dc.subjecttransmembrane proteins
dc.subjectenzymes
dc.subjectdrug development
dc.subjectcontraception
dc.titleAdvances in non-hormonal male contraception targeting sperm motilityen
dc.typeArtigo
dcterms.licensehttp://www.oxfordjournals.org/access_purchase/self-archiving_policyb.html
dcterms.rightsHolderOxford Univ Press
unesp.author.orcid0000-0001-7459-9173[3]

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