Estrogen is related with the low morbidity associated with obstructive sleep apnea hypopnea syndrome (OSAS) in women, but the underlying mechanisms remain largely unknown. In this study, we examined the relationship between OSAS and estrogen related receptor-α (ERR-α). We found that the expression levels of ERR-α and Myh7 were both downregulated in palatopharyngeal tissues from OSAS patients. In addition, we report that ERR-α is dynamically expressed during differentiation of C2C12 myoblasts. Knockdown of ERR-α via instant siRNA resulted in reduced expression of Myh7, but not Myh4. Furthermore, differentiation of C2C12 cells under 3% chronic intermittent hypoxia, a model resembling human OSAS, was impaired and accompanied by a obvious reduction in Myh7 expression levels. Moreover, activation of ERR-α with 17β-estradiol (E2) increased the expression of Myh7, whereas pretreatment with the ERR-α antagonist XCT790 reversed the E2-induced slow fiber-type switch. A rat ovariectomy model also demonstrated the switch to fast fiber type. Collectively, our findings suggest that ERR-α is involved in estrogen-mediated OSAS by regulating Myhc-slow expression. The present study illustrates an important role of the estrogen/ERR-α axis in the pathogenesis of OSAS, and may represent an attractive therapeutic target, especially in postmenopausal women.

Background: The Valsalva maneuver (VM) is widely used in daily life, and has been reported to cause high intraocular pressure (IOP). This study aimed to assess changes in IOP, the Schlemm's canal (SC), autonomic nervous system activity, and iridocorneal angle morphology in healthy individuals during different phases of the VM. Methods: The high frequency (HF) of heart rate (HR) variability, the ratio of low frequency power (LF) and HF (LF/HF), heart rate (HR), IOP, systolic (SBP) and diastolic blood pressure (DBP), the area of SC (SCAR), pupil diameter (PD), and some iridocorneal angle parameters (AOD500, ARA750, TIA500 and TISA500) were measured in 29 young healthy individuals at baseline, phase 2, and phase 4 of the VM. SBP and DBP were measured to calculate mean arterial pressure (MAP) and mean ocular perfusion pressure (MOPP). HF and the LF/HF ratio were recorded using Kubios HR variability premium software to evaluate autonomic nervous system activity. The profiles of the anterior chamber were captured by a Spectralis optical coherence tomography device (anterior segment module). Results: Compared with baseline values, in phase 2 of the VM, HR, LF/HF, IOP (15.1 ± 2.7 vs. 18.8 ± 3.5 mmHg, P < 0.001), SCAR (mean) (7712.112 ± 2992.14 vs. 8921.12 ± 4482.79 μm 2 , P = 0.039), and PD increased significantly, whereas MOPP, AOD500, TIA500, and TISA500 decreased significantly. In phase 4, DBP, MAP, AOD500, ARA750, TIA500and TISA500 were significantly lower than baseline value, while PD and HF were remarkably larger than baseline. The comparison between phase 2 and phase 4 showed that HR, IOP (18.8 ± 3.5 vs. 14.7 ± 2.9 mmHg, P < 0.001) and PD decreased significantly from phase 2 to phase 4, but there were no significant differences in other parameters. Conclusions: The expansion and collapse of the SC in different phases of the VM may arise from changes in autonomic nervous system activity. Further, the effects of the VM on IOP may be attributed to changes in blood flow and ocular anatomy. Trial registration: This observational study was approved by the ethics committee of Tongji Hospital (Registration Number: ChiCTR-OON-16007850, Date: 01.28.2016).

Purpose To estimate the outflow facility coefficient (C) as a function of Schlemm's canal cross-sectional area (SCAR) in healthy subjects using noninvasive oculopression tonometry (OPT). Methods In 25 healthy volunteers, intraocular pressure (IOP) decay values were recorded by a ophthalmodynamometer, with a fixed external force (0.15 N) on the inferior-temporal eyelid, every 10 seconds, for four minutes, and again after a 30-minute rest. Schlemm's canal profile images and IOP were obtained pre-procedurally (baseline), immediately (T0), and at 1-minute intervals post-procedurally (T1, T2, T3, and T4). C was calculated for different IOPs. The SCAR, coronal, and the meridional diameter of Schlemm's canal were calculated. Results Mean C 0 for the maximum IOP was 0.020 ± 0.017 µL/min/mm Hg; mean C was 0.018 ± 0.0071 and 0.058 ± 0.0146 µL/min/mm Hg at 40 and 20 mm Hg, respectively. C was nonlinearly dependent on the IOP ( R 2 = 0.945). The SCAR was 5440 ± 3140.82, 3947.6 ± 2246.8, and 5375.7 ± 2662.7 µm 2 at baseline, T0, and T4, respectively. The coronal diameter of SC decreased significantly from the baseline (33.02 ± 11.3 µm) to T0 (26.6 ± 9.37 µm) and recovered at T4 (32.3 ± 9.53 µm). The SCAR and IOP correlated significantly throughout ( R 2 = 0.9944; P < 0.001). C0 significantly correlated with the SCAR at baseline and with changes in the SCAR and IOP from T0 to T4. Conclusions Schlemm's canal dimensions are responsible for the IOP-dependent mechanical forces, and these changes appear to directly affect outflow facility.