Apocynin and raisanberine alleviate intermittent hypoxia induced abnormal StAR and 3β-HSD and low testosterone by suppressing endoplasmic reticulum stress and activated p66Shc in rat testes

We hypothesized that hypoxia induced testicular damage is mediated by an activated NADPH oxidase (NOX), therefore, APO (apocynin) an inhibitor of NOX and raisanberine (RS), a calcium influx inhibitor were tested if they could attenuate hypoxic toxicity to the testis. Male Sprague-Dawley rats were exposed to hypoxia (10 ± 0.5% O2) for 17 d and intervened with APO and RS in the last 6 d. Histological changes and expression of pro-inflammation factors were evaluated in vivo. Biomarkers in isolated Leydig cells incubated with H2O2 were also assayed in vitro. Hypoxic rats displayed lower serum testosterone and higher LH and FSH. Upregulation of p22/p47phox, NOX2, MMP9, PERK and p66Shc was associated with downregulation of StAR, 3β-HSD and Cx43 in the hypoxia testis, revealed by Western blot and immunohistochemical assay, respectively. APO and RS at least partially normalize hypoxia caused male hypogonadism by suppressing ER stress, and p66Shc in testes.

► Hypoxia exposed in rats causes low testosterone and high LH and FSH in serum.
► Downregulated StAR and 3β-HSD were found relating to NOX activation in testes.
► The testicular changes are due to an increase in pro-inflammatory factors.
► Upregulation of PERK, p66SHc and Nox2 and downregulation of Cx43 were found.
► These changes are blunted by apocynin and raisanberine, a Ca2+ influx inhibitor.