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Nayyab S, Gervasi MG, Tourzani DA, et al. TSSK3, a novel target for male contraception, is required for spermiogenesis. Mol Reprod Dev. 2021;88(11):718-730doi: 10.1002/mrd.23539.
Nayyab, S., Gervasi, M. G., Tourzani, D. A., Caraballo, D. A., Jha, K. N., Teves, M. E., Cui, W., Georg, G. I., Visconti, P. E., & Salicioni, A. M. (2021). TSSK3, a novel target for male contraception, is required for spermiogenesis. Molecular reproduction and development, 88(11), 718-730. https://doi.org/10.1002/mrd.23539
Nayyab, Saman, et al. "TSSK3, a novel target for male contraception, is required for spermiogenesis." Molecular reproduction and development vol. 88,11 (2021): 718-730. doi: https://doi.org/10.1002/mrd.23539
Nayyab S, Gervasi MG, Tourzani DA, Caraballo DA, Jha KN, Teves ME, Cui W, Georg GI, Visconti PE, Salicioni AM. TSSK3, a novel target for male contraception, is required for spermiogenesis. Mol Reprod Dev. 2021 Nov;88(11):718-730. doi: 10.1002/mrd.23539. Epub 2021 Oct 08. PMID: 34623009.
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Mol Reprod Dev. 2021 Nov;88(11):718-730. doi: 10.1002/mrd.23539. Epub 2021 Oct 08.

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

Molecular reproduction and development

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

Affiliations

  1. Department of Veterinary & Animal Sciences, University of Massachusetts-Amherst, Amherst, Massachusetts, USA.
  2. Department of Molecular and Cellular Biology Graduate Program, University of Massachusetts-Amherst, Amherst, Massachusetts, USA.
  3. Biotechnology Training Program, University of Massachusetts-Amherst, Amherst, Massachusetts, USA.
  4. Instituto de Ecología, Genética y Evolución (IEGEBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
  5. Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
  6. Division of Biotechnology Review and Research IV, Office of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
  7. Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia, USA.
  8. Animal Models Core Facility, Institute for Applied Life Sciences (IALS), University of Massachusetts-Amherst, Amherst, Massachusetts, USA.
  9. Department of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, University of Minnesota, Minneapolis, Minnesota, USA.

PMID: 34623009 DOI: 10.1002/mrd.23539

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.

© 2021 Wiley Periodicals LLC.

Keywords: TSSK3; evolution; fertilization; intronless gene; kinases; nonhormonal male contraceptive; sperm; spermatogenesis; testis-specific

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