Orchidectomy exacerbates respiratory instability induced by intermittent hypoxia in C57BL6/J mice

Abstract

IntroductionSleep apnea (SA) is characterized by obstructions of the airways or cessation of breathing during sleep leading to intermittent hypoxia (IH). In rodents, exposure to IH induces strong oxidative stress in the peripheral chemoreceptors (the main oxygen sensors inducing cardiorespiratory responses to IH), which increase their activity leading to instability of the respiratory control system, ultimately increasing the frequency of apnea during sleep. In human, patients with SA have low circulating testosterone levels and the severity of SA in overweight patients is negatively correlated with testosterone levels. However, testosterone can reduce oxidative stress in certain animal and clinical models. We therefore tested the hypothesis that testosterone modulates the respiratory instability induced by HI.MethodWe used intact (Sham) or orchidectomized (ORX) C57BL/6J male mice exposed for 14 days to IH (12h / day, 10 cycles / h, 6% nadir oxygen) or in normoxia (Nx). We used whole body plethysmography on freely behaving and non‐anesthetized mice to measure the frequency of apneas and sighs as well as the length of the apneas during sleep. The antioxidant activity of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were then measured in plasma.ResultsIH increases the frequency of post‐sigh apneas as well as the length of post‐sigh and spontaneous apneas in Sham and ORX mice. In ORX‐IH mice, the length of post‐sigh apneas was further increased, and there was a higher proportion of multiple apneas after a single sigh. In Nx mice, GPx activity was increased by ORX, this effect was not present in mice exposed to IH.ConclusionThe lack of testosterone in ORX mice amplifies the effects of IH on respiratory stability during sleep and alters the regulation of GPx activity in plasma. Further studies are needed to better understand the underlying mechanism