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Spermatogenesis is a complex and elaborate differentiation process and is vital for male fertility. Sertoli cells play a major role in fertility and induce spermatogenesis by protecting, nourishing, and supporting germ cells. It has been speculated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could directly affect the male reproductive system, and therefore heredity and fertility. The similarity of SARS-CoV-2 to SARS-CoV could confirm this hypothesis because both viruses use angiotensin-converting enzyme (ACE2) as the receptor to enter human cells. ACE2 is expressed by Sertoli cells and other testicular cells, therefore COVID-19 has the potential to impair fertility by destroying Sertoli cells. This hypothesis should be evaluated and confirmed by monitoring fertility in patients with COVID-19.

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KLF4 is a transcription factor involved in proliferation, differentiation, apoptosis and somatic cell reprogramming; thus, it has a critical role in accurate spermatogenesis. Currently, how KLF4 regulates the Wnt cascade has been discussed and suggested that this connection be related to TERT and Ctnnb1, but its regulatory mechanisms are still very vague. Contrary to the data of many researchers who have identified KLF4 as a factor in maintaining stemness, we have stated that KLF4 is a differentiating factor that its expression increases during spermatogenesis. Furthermore, we show how the regulatory loops of KLF4, TERT and Ctnnb1 through the Wnt pathway is age-dependent. Data collected during immunohistochemistry, immunocytochemistry and Fluidigm real-time RT-PCR besides in silico analyzes indicate that the performance of KLF4 is context-dependent.