Zbtb40 Deficiency Leads to Morphological and Phenotypic Abnormalities of Spermatocytes and Spermatozoa and Causes Male Infertility

• Published in: Cells (Basel, Switzerland) Vol. 12; no. 9; p. 1264
• Main Authors: Cui, Yinghong, Zhou, Mingqing, He, Quanyuan, He, Zuping
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26.04.2023; MDPI
• Subjects: Animals; Apoptosis; Biosynthesis; Body weight; DNA-Binding Proteins - genetics; Double-strand break repair; Epididymis; Evolution; Fertility; Flagella; Gene regulation; Gene therapy; Genes; Humans; Infertility; Infertility, Male - genetics; Male; male infertility; Mice; Mice, Knockout; Morphology; Mutation; Physical characteristics; Proteins; Semen; Sex chromosomes; Sperm; Spermatids; Spermatocytes; Spermatogenesis; Spermatozoa; telomere length; Telomeres; Testes; Testis; Zbtb40 knockout; ZBTB40 mutation; spermatocytes; spermatids; ZBTB40 mutation; Zbtb40 knockout; male infertility; telomere length
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12091264

Studies on the gene regulation of spermatogenesis are of unusual significance for maintaining male reproduction and treating male infertility. Here, we have demonstrated, for the first time, that a loss of ZBTB40 function leads to abnormalities in the morphological and phenotypic characteristics of mouse spermatocytes and spermatids as well as male infertility. We revealed that Zbtb40 was expressed in spermatocytes of mouse testes, and it was co-localized with γH2AX in mouse secondary spermatocytes. Interestingly, spermatocytes of knockout mice had longer telomeres, compromised double-strand break (DSB) repair in the sex chromosome, and a higher apoptosis ratio compared to wild-type (WT) mice. The testis weight, testicular volume, and cauda epididymis body weight of the male mice were significantly lower than in WT mice. Mating tests indicated that male mice were able to mate normally, but they failed to produce any pups. Notably, sperm of mice showed flagellum deformities and abnormal acrosome biogenesis. Furthermore, a ZBTB40 mutation was associated with non-obstructive azoospermia. Our results implicate that ZBTB40 deficiency leads to morphological and phenotypic abnormalities of spermatocytes and spermatids and causes male infertility. This study thus offers a new genetic mechanism regulating mammalian spermatogenesis and provides a novel target for gene therapy in male infertility.