Affiliation:
1. The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Hunan Normal University School of Medicine, Changsha 410013, China
2. The Research Center of Reproduction and Translational Medicine of Hunan Province, Changsha 410013, China
3. The Manufacture-Based Learning & Research Demonstration Center for Human Reproductive Health New Technology of Hunan Normal University, Changsha 410013, China
Abstract
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 Zbtb40 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 Zbtb40+/− male mice were significantly lower than in WT mice. Mating tests indicated that Zbtb40+/− male mice were able to mate normally, but they failed to produce any pups. Notably, sperm of Zbtb40+/− 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.
Funder
National Nature Science Foundation of China
Major Scientific and Technological Projects
Key Grant of Research and Development in Hunan Province
Developmental Biology and Breeding
High Level Talent Gathering Project in Hunan Province
Natural Science Foundation of Hunan Province of China
Health Commission Foundation of Hunan Province
Cited by
3 articles.
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