Effects of intrauterine intermittent hypoxia on skeletal muscle in offspring rats

Abstract

Gestational intermittent hypoxia (IH), a hallmark of OSA, alters the offspring's respiratory neural control and diaphragm contractile function. Thus, we aimed to investigate the effects of gestational IH on the muscle development and metabolism of geniohyoid (GH), which is innervated by the respiratory-related hypoglossal nerve and plays a role in tongue traction and suckling, in male offspring rats compared with masseter (MAS), the largest masticatory muscle. Pregnant Sprague-Dawley rats were exposed to IH (3-min periods of 4–21% O2) compared to Normoxia for 8 hours/day during gestational days 7–20. GH and MAS from 35-day-old male offspring (n = 6 /group) were analyzed. Data were statistically analyzed with Welch's t-test. Gestational IH reduced type IIA fiber size in GH, but not in MAS. Western blot analysis showed that gestational IH induced significant downregulation of PGC1ɑ protein in GH, but not in MAS. Moreover, optic atrophy 1 and mitofusin-2 proteins, Mitochondrial ATP synthase subunit alpha, and transcriptional factor A (TFAM) were decreased while mitochondrial fission 1 protein levels were increased in the GH of gestational IH-offspring. Our results suggest mitochondrial metabolism impairment and oxidative myofibers alteration of the GH from gestational IH-preadolescent offspring, owing to the susceptibility of GH mitochondria to gestational IH which might be influenced by hypoglossal nerve innervation.