TSSK3, a novel target for male contraception, is required for spermiogenesis

Saman Nayyab, María G. Gervasi, Darya A. Tourzani, Diego A. Caraballo, Kula N. Jha, Maria E. Teves, Wei Cui, Gunda I. Georg, Pablo E. Visconti, Ana M. Salicioni

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

We have previously shown that members of the family of testis-specific serine/threonine kinases (TSSKs) are post-meiotically expressed in testicular germ cells and in mature sperm in mammals. The restricted post-meiotic expression of TSSKs as well as the importance of phosphorylation in signaling processes strongly suggest that TSSKs have an important role in germ cell differentiation and/or sperm function. This prediction has been supported by the reported sterile phenotype of the TSSK6 knock-out (KO) mice and of the double TSSK1/TSSK2 KO. The aim of this study was to develop KO mouse models of TSSK3 and to validate this kinase as a target for the development of a male contraceptive. We used CRISPR/Cas9 technology to generate the TSSK3 KO allele on B6D2F1 background mice. Male heterozygous pups were used to establish three independent TSSK3 KO lines. After natural mating of TSSK3 KO males, females that presented a plug (indicative of mating) were monitored for the following 24 days and no pregnancies or pups were found. Sperm numbers were drastically reduced in all three KO lines and, remarkably, round spermatids were detected in the cauda epididymis of KO mice. From the small population of sperm recovered, severe morphology defects were detected. Our results indicate an essential role of TSSK3 in spermiogenesis and support this kinase as a suitable candidate for the development of novel nonhormonal male contraceptives.

Original languageEnglish (US)
Pages (from-to)718-730
Number of pages13
JournalMolecular Reproduction and Development
Volume88
Issue number11
Early online dateOct 8 2021
DOIs
StatePublished - Oct 8 2021

Bibliographical note

Funding Information:
This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development 5P50HD093540 (to P.E.V. and G.I.G.); and by the Male Contraceptive Initiative Sokal Award MCI # 2020‐304 (to P.E.V.) and a Trainee Fellowship MCI # 2020‐B02 (to S.N). The authors would also like to thank NIH for partial support from National Research Service Award T32 GM108556 (Biotechnology Training Program funding to D.A.T.). The VCU Massey Cancer Center Microscopy Core Facility is partially supported by the NIH‐NCI Cancer Center Support Grant P30 CA016059.

Publisher Copyright:
© 2021 Wiley Periodicals LLC

Keywords

  • TSSK3
  • evolution
  • fertilization
  • intronless gene
  • kinases
  • nonhormonal male contraceptive
  • sperm
  • spermatogenesis
  • testis-specific

Fingerprint

Dive into the research topics of 'TSSK3, a novel target for male contraception, is required for spermiogenesis'. Together they form a unique fingerprint.

Cite this