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

• Autores: Nayyab, Saman; Gervasi, María G.; Tourzani, Darya A.; Caraballo, Diego Alfredo; Jha, Kula N.; Teves, Maria E.; Cui, Wei; Georg, Gunda I.; Visconti, Pablo E.; Salicioni, Ana M.
• Año de publicación: 2021
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: EVOLUTION; FERTILIZATION; INTRONLESS GENE; KINASES; NONHORMONAL MALE CONTRACEPTIVE; SPERM; SPERMATOGENESIS; TESTIS-SPECIFIC; TSSK3
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: Nayyab, Saman. University of Massachussets; Estados Unidos
Fil: Gervasi, María G.. University of Massachussets; Estados Unidos
Fil: Tourzani, Darya A.. University of Massachussets; Estados Unidos
Fil: Caraballo, Diego Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina
Fil: Jha, Kula N.. No especifíca;
Fil: Teves, Maria E.. University of Virginia; Estados Unidos
Fil: Cui, Wei. University of Massachussets; Estados Unidos
Fil: Georg, Gunda I.. University of Minnesota; Estados Unidos
Fil: Visconti, Pablo E.. University of Massachussets; Estados Unidos
Fil: Salicioni, Ana M.. University of Massachussets; Estados Unidos