Respiratory instability in neonatal rats after exposure to gestational intermittent hypoxia

Abstract

Sleep disordered breathing (SDB) during pregnancy is a growing concern because it causes adverse outcomes for infant offspring. Recently, our lab developed a rat model of SDB during pregnancy in which pregnant dams were exposed to gestational intermittent hypoxia (GIH; 15 episodes/hr of 10.5% oxygen for 8h daily from days 10-20 of pregnancy). Control dams were exposed in parallel to gestational intermittent normoxia (GNX). We found that male (but not female) GIH offspring had increased apneas in adulthood compared to their GNX control counterparts. Thus, in this study, we tested the hypothesis that GIH would increase respiratory instability (i.e. increase the number of apneas) in neonatal male, not female, offspring. Plethysmography was performed on GIH and GNX male and female pups at postnatal (P) days 0, 10, and 15, and the number of apneas was quantified. An apnea was defined as two missed breaths (2x the average period between breaths). Preliminary data suggest that apnea frequency was sexually dimorphic and changed both with development and treatment. At P10 and P15 male GIH offspring had more apneas compared to GNX offspring (p<0.05). However, at P0, male GIH offspring (16 ± 2.4 apneas/10m) had surprisingly fewer apneas compared to GNX offspring (28 ± 1.9 apneas/10m). In female offspring in contrast, there was no difference in apnea frequency between GIH and GNX treatment at P0, but at P10 and P15 respectively, female GIH offspring (17 ± 2.8 and 9 ± 2.3 apneas/10m) had more apneas compared to their GNX counterparts (8 ± 1.2 and 2.9 ± 0.57 apneas/10m). Apnea frequency decreased with increasing age in both sexes, regardless of GIH and GNX treatment. Together, as expected, these results suggest that the increased apnea phenotype observed in the adult GIH male emerges as early as postnatal day 10. Unexpected however is the observation that female neonatal GIH offspring also experience respiratory instability in during the postnatal period despite its absence in adult female GIH offspring. Studies are currently underway to better understand the mechanisms underlying these sex differences in respiratory neural control, and the protective responses utilized by adult female GIH offspring to mitigate these respiratory deficits induced by intermittent hypoxia exposure in utero. R01 HL142752 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.