Kruppel-like factor 4 expression in normal and pathological human testes

Abstract

Krüppel-like factor 4 (KLF4) is a transcription factor involved in many cellular and developmental processes such as terminal differentiation of cells and carcinogenesis. Mice lacking KLF4 die post-natally due to skin barrier deficiencies and exhibit several additional cellular defects. The adult rodent testis expresses high levels of Klf4 mRNA. Using in situ hybridization, we previously localized most of the Klf4 mRNA to round spermatids in mice. Moreover, in rodent Sertoli cells, Klf4 is strongly inducible by FSH. Here, we show by northern blot analysis that the human testis also strongly expresses KLF4. Applying immunohistochemistry, we localized KLF4 protein to the nuclei of round spermatids during normal spermatogenesis stages II–IV. Analysing round spermatid maturation arrests, strong cytoplasmic staining could be seen in two samples. We failed to detect KLF4 in human Sertoli cells. Most human Leydig cells expressed KLF4 at high levels in the nucleus. However, some individual Leydig cells lacked KLF4, suggesting different functional states of the Leydig cells. The strong expression of KLF4 in the human testis and the importance of KLF4 in several mouse tissues suggest a significant role for KLF4 in the human testis. A first hint at a role for KLF4 during spermiogenesis could be the altered subcellular localization of the protein during arrested spermiogenesis.