At genomic DNA levels, ZBTB43 safeguards genomic integrity by regulating de novo DNA methylation at CG-containing purine–pyrimidine repeats, removing Z-DNA, and preventing DNA double-strand breaks in mouse prospermatogonia.375 It is interesting that ZBTB43 expression is also involved in cancer stemness in humans.376 In addition, male reproductive aging is associated with the capacity decline of SSC niche,363,377 thus, older males are often accompanied by a decrease in reproductive function. This evidence concerns the gene ZBTB43 and cancer.