The hypoxic microenvironment of
cryptorchidism is an important factor in the impairment and
fibrosis of Sertoli cells which result in blood-testis barrier (BTB) destruction and spermatogenesis loss. Recent studies have shown that
melatonin, a well-known pineal
hormone exerts beneficial effects against pathological
fibrosis in a various of organs. However, it is still unknown whether
melatonin can regulate
hypoxia-induced
fibrosis of Sertoli cells. In this study we evaluate
melatonin levels, and its synthesizing
enzymes, AANAT and
HIOMT expression patterns in canine
cryptorchidism and contralateral normal testis. Results show abdominal testes presented low
melatonin levels and AANAT and
HIOMT expression compared with testes located in the scrotum. Moreover, we established a
hypoxia-induced
fibrosis model in canine Sertoli cells induced by
cobalt chloride (CoCl2) and found that
melatonin inhibited the EMT markers expression and ECM production as well as Hif-1α expression of Sertoli cells in a dose-dependent manner. Furthermore, use of Lificiguat (synonyms YC-1, Hif-1α inhibitor) to interfere with the Hif-1α pathway showed a similar effect with
melatonin suppression of the
fibrosis in Sertoli cells. The results indicate that
melatonin supplementation can alleviate the
fibrosis process of Sertoli cells caused by
hypoxia, which is associated with regulating the inhibition of Hif-1α signaling.