Intermittent Hypoxia Induces Impaired Craniofacial and Muscular Growths in Rats

Objectives: An altered pattern of maxillofacial growth is observed in cases of pediatric obstructive sleep apnea syndrome (POSA). Impaired function and morphology of the tongue are associated with POSA, and intermittent hypoxia (IH) is a main characteristic. The aim of this study was to examine changes in dentofacial growth and tongue musculature in growing rats exposed to IH.
Methods: Seven-week-old rats were exposed to IH at a rate of 20 cycles/h (nadir of 4% O₂ to peak of 21% O₂ with 0% CO₂) for 8 h/day for 6 weeks. Linear measurements on cephalometric radiographs were used to compare the maxillofacial growth of IH and sham-operated rats. Both study models and micro-computed tomography (micro-CT) images of jaws were obtained to examine the dental arch morphology and measure the tongue size. Immunoblots of the tongue and geniohyoid muscles for Akt/mTOR signaling were obtained to check the pathway of muscular hypertrophy.

Results: According to the cephalometric analysis, the gonial angle (-4.4%, p < 0.05) and the ramus (-5.5%, p < 0.05) were smaller in the mandibles of the IH rats compared to the controls, even though both groups had equal increases in body weight. The morphometric analysis of dentition showed a significantly wider mandibular dental arch (M1, +6.4%; M2, +4.5%) and a narrower maxillary arch (M2, -3.2%; M3, -2.9%) in the IH group compared to the control group. The relative width of the tongue compared to the mandible significantly increased in the IH rats (+6.8%, p < 0.05). Immunoblots showed activation of Akt phosphorylation in both the tongue and geniohyoid muscles in the IH rats, but not in the gastrocnemius muscle.
Conclusions: This study is the first to demonstrate retarded maxillofacial growth with morphological discrepancy of the dental arch under IH. We used Akt/mTOR signaling to identify muscular hypertrophy of the tongue induced by IH.