Orchiectomy exacerbates sleep-disordered breathing induced by intermittent hypoxia in mice

Ganouna-Cohen, Gauthier; Marcouiller, François; Bairam, Aïda; Joseph, Vincent

doi:10.1016/j.resp.2023.104052

Cited by 3 publications

(1 citation statement)

References 37 publications

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“…It should nonetheless be emphasized that reports from the literature show that variability of physiological or biological parameters in female mice is not different than what is observed in males, and sometimes even lower, across a wide range of variables [ 15 , 16 ], and ignoring potential variability associated with the estrous cycle is perfectly acceptable in preclinical studies. While repeating the experiments in ovariectomized female mice is warranted to understand the roles of ovarian hormones and their interaction with DIO, the roles of testosterone in males on respiratory and metabolic responses in SDB should not be overlooked [ 17 , 18 ]. Fourthly, sleep studies were conducted for only 6 hours during the light phase.…”

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Sleep apnea and diet-induced obesity—the female advantage on the spotlight

Badran

Joseph

2023

Sleep

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confidence: 99%

Sleep apnea and diet-induced obesity—the female advantage on the spotlight

Badran

Joseph

2023

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Concomitant effects of orchiectomy and intermittent hypoxia on hepatic oxidative stress, expression of flavin-containing monooxygenases and transcriptomic profile in mice

Cohen

Marcouiller

Joly-Beauparlant

et al. 2023

Preprint

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Intermittent hypoxia induces oxidative stress and alters hepatic metabolism, likely underlying the association of sleep apnea with non-alcoholic fatty liver disease. In male patients with sleep apnea, metabolic or liver diseases, the levels of testosterone are reduced, and in patients with metabolic diseases, low levels of testosterone are associated with oxidative stress. To assess potential interactions between testosterone and IH on hepatic oxidative stress we used sham-operated or orchiectomized (ORX) mice exposed to normoxia (Nx) or IH (6% O2, 12 cycles/h, 12h/day) for 2 weeks. The activity of prooxidant (NADPH oxidase: NOX), antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase: SOD, Cat, GPx), lipid peroxidation (MDA concentration) and the total concentration of glutathione (GSH) were measured in liver. IH induced a prooxidant profile of enzyme activity (lower SOD activity and higher NOX/SOD and NOX/Cat activity ratio) without altering hepatic MDA and GSH content. Using RNA sequencing followed by a pathway enrichment analysis we identified putative hepatic genes underlying the interactions between IH and testosterone. ORX and IH altered the expression of genes involved in oxidoreductase activities, cytochromes dependent pathways, and glutathione metabolism. Among the genes upregulated in ORX-IH mice, the flavin-containing monooxygenases (FMO) are particularly relevant since these are potent hepatic antioxidant that could help prevent overt oxidative stress in ORX-IH mice.

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Loss of testosterone induces postprandial insulin resistance and increases the expression of the hepatic antioxidant flavin‐containing monooxygenases in mice exposed to intermittent hypoxia

Ganouna‐Cohen,

Marcouiller,

Blachot‐Minassian

et al. 2024

Acta Physiologica

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AimWe tested the hypothesis that low testosterone alters the effects of intermittent hypoxia (IH) on glucose homeostasis, hepatic oxidative stress, and transcriptomic profile in male mice.MethodsWe used sham‐operated or orchiectomized (ORX) mice exposed to normoxia (Nx) or IH for 2 weeks. We performed fasting insulin and glucose tolerance tests and assessed fasting and postprandial insulin resistance with the HOMA‐IR. The activity of hepatic prooxidant (NADPH oxidase—NOX), antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase—SOD, Cat, GPx), lipid peroxidation (MDA concentration), and the total concentration of glutathione (GSH) were measured under postprandial conditions. mRNA sequencing and pathway enrichment analyses were used to identify hepatic genes underlying the interactions between IH and testosterone.ResultsIn Sham mice, IH improves fasting insulin sensitivity and glucose tolerance, while there are no effects of IH in ORX mice. In ORX mice, IH induces postprandial hyperinsulinemia, insulin resistance, and a prooxidant profile of enzyme activity (low SOD activity) without altering hepatic MDA and GSH content. ORX and IH altered the expression of genes involved in oxidoreductase activities, cytochromes‐dependent pathways, and glutathione metabolism. Among the genes upregulated in ORX‐IH mice, the flavin‐containing monooxygenases (FMO) are particularly relevant since these are potent hepatic antioxidants that could help prevent overt oxidative stress in ORX‐IH mice.ConclusionLow levels of testosterone in male mice exposed to IH induce post‐prandial hyperinsulinemia and insulin resistance and determine the mechanisms by which the liver handles IH‐induced oxidative stress.

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Orchiectomy exacerbates sleep-disordered breathing induced by intermittent hypoxia in mice

Cited by 3 publications

References 37 publications

Sleep apnea and diet-induced obesity—the female advantage on the spotlight

Sleep apnea and diet-induced obesity—the female advantage on the spotlight

Concomitant effects of orchiectomy and intermittent hypoxia on hepatic oxidative stress, expression of flavin-containing monooxygenases and transcriptomic profile in mice

Loss of testosterone induces postprandial insulin resistance and increases the expression of the hepatic antioxidant flavin‐containing monooxygenases in mice exposed to intermittent hypoxia

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