Testis tumours, including germ cell and stromal cell tumours, are the most common types of cancer in men between the ages of 15 and 35. The incidence of testis tumours is approximately four new cases per 100,000 men per year in Canada (CCS, 2017). Importantly, this prevalence has increased by a factor of three over the past four decades. Several risk factors have been identified, including cryptorchidism (undescended testis), carcinoma in situ, contralateral tumour history and infertility. Very rare in the general population, Leydig cell tumours represent only 1%-3% of all cases of testicular tumours in men (Al-Agha & Axiotis, 2007). In rats, the prevalence of Leydig cell tumours is more common and ranges from 5.3% for the Sprague-Dawley to 76.8% for the F344 strain. However, there is a detection bias in favour of rats where the diagnosis of Leydig cell tumours is based on histological evaluation. In humans, such diagnosis is generally based on palpation and development of symptoms such as gynaecomastia or fertility problems (Cook et al., 1999). In addition, others have questioned the rarity of Leydig cell tumours and suggest that they are more common with an incidence of 18% of all surgically removed testicular cancers (Leonhartsberger et al., 2011). Indeed,
Gap junctions made by connexins within the adult testis are essential for communication between Sertoli cells and for spermatogenesis. Sertoli cells play an important role in supporting germ cells differentiation and maturation into spermatozoa. Connexin43 (Cx43) is the most abundant and important connexin of the testis. We have shown previously that the expression of
Cx43
is being regulated by SOX and AP-1 transcription factors in Sertoli cells. However, additional regulatory elements being able to recruit orphan nuclear receptors may be involved. Since SOX and SF-1 transcription factors have been shown to cooperate to regulate gene expression in Sertoli cells, we wondered if such mechanism could be involved in the activation of
Cx43
expression. Thus, the activity of the
Cx43
promoter was measured by co-transfections of luciferase reporter plasmid constructs with different expression vectors for transcription factors in the TM4 Sertoli cell line. The recruitment of SF-1 to the proximal region of the
Cx43
promoter was evaluated by chromatin immunoprecipitation. Our results indicate that SOX8 and SF-1, as well as SOX9 and Nur77, cooperate to activate the expression of
Cx43
and that SF-1 is being recruited to the −132 to −26 bp region of the
Cx43
promoter. These results allow us to have a better understanding of the mechanisms regulating
Cx43
expression and could explain some disturbances in communication between Sertoli cells responsible for impaired fertility.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.