Chronic sleep deprivation is associated with delayed puberty onset in rats, activation of proinflammatory cytokines and gut dysbiosis

Abstract

Chronic sleep deprivation (CSD) in adolescents has become a trend with adverse health outcomes. Previous studies have demonstrated that sleep deprivation causes inflammation, alters puberty onset, and changes the gut microbiome composition; however, the relationship between these is still unknown. Therefore, we hypothesized that CSD delays the onset of puberty via elevating proinflammatory cytokines and alter ation of gut microbiome composition. Using the modified multiple platform method, we conducted a 4-week CSD experiment in juvenile rats and assessed pubertal markers, antioxidant activity, cytokine levels, and gut microbiome profiles. CSD significantly reduces body weight, delays onset of puberty, and elevated antioxidant enzyme activities in both sexes. In the sleep-deprivation female (SDF) rats, plasma levels of lipopolysaccharide-binding protein (LBP), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were significantly elevated; mRNA levels of TNF-alpha and IL-1 beta were also significantly elevated in the colon and reproductive organs, respectively. In the sleep-deprivation male (SDM) rats, only plasma levels of IL-6 were elevated considerably; in addition, mRNA levels of IL-1 beta and TNF-alpha were also significantly elevated in the colon and reproductive organs, respectively. Gut microbiome analysis revealed that the predominant bacteria at the genus level were Muribaculaceae, Prevotellaceae UCG-001, and Ruminococcaceae UCG-005 in the SDF rats; Prevotellaceae NK3B31, Ruminococcaceae UCG-010, Eubacterium coprostanoligenes, and Shuttleworthia in the SDM rats. CSD rats with abundant genera were positively correlated with antioxidant enzyme activities and mRNA levels of proinflammatory cytokines. Overall, CSD is associated with delayed puberty onset, possibly via an increase in the expression levels of proinflammatory cytokines and altering the gut microbiome composition, indicating proinflammatory cytokines and gut microbiome play an important role in pubertal timing change. These findings may guide the future studies to intervene sleep deprivation-related delays in the onset of puberty.