Chronic prenatal hypoxia impairs cochlear development, a mechanism involving connexin26 expression and promoter methylation.

Chronic prenatal hypoxia is a damaging to fetal development and may have various consequences, including hearing loss. Connexin 26 (Cx26) is one of the major protein subunits required for gap junction formation, and has an important role in maintaining homeostasis in the cochlea and normal hearing. Cx26 mutation and expression abnormality are closely associated with inherited nonsyndromic deafness, but the association between Cx26 and prenatal hypoxia is less established. The present study aimed to examine Cx26 expression and aberrant methylation the Cx26 promoter region in the cochlea from rats exposed to chronic prenatal hypoxia. Hematoxylin and eosin staining demonstrated that the number of hair cells in the organ of Corti were less in the hypoxia group. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis revealed that protein and mRNA levels of Cx26 were decreased in the hypoxia group compared with the control group. Further bisulfite sequencing analysis revealed that prenatal hypoxia significantly increased the methylation status of the promoter region of the Cx26 gene. These results demonstrate that chronic prenatal hypoxia caused hearing impairment, and suggest that promoter region hypermethylation and expression downregulation of Cx26 underlie the mechanism of action.