Intermittent hypoxia in neonatal rodents affects facial bone growth

Abstract

Preterm human infants often show periodic breathing (PB) or apnea of prematurity (AOP), breathing patterns which are accompanied by intermittent hypoxia (IH). We examined cause-effect relationships between transient IH and reduced facial bone growth using a rat model. Neonatal pups from 14 timed pregnant Sprague-Dawley rats were randomly assigned to an IH condition, with oxygen altering between 10% and 21% every 4 min for 1 h immediately after birth, or to a litter-matched control group. The IH pups were compared with their age- and sex-matched control groups in body weight (WT), size of facial bones and nor-epinephrine (NE) levels in blood at 3, 4, and 5-weeks. Markedly increased activity of osteoclasts in sub-condylar regions of 3-week-old IH-treated animals appeared, as well as increased numbers of sympathetic nerve endings in the same region of tissue sections. Male IH-pups showed significantly higher levels of NE levels in sera at 3, 4 as well as 5-week-old time points. NE levels in 4- and-5-week-old female pups did not differ significantly. Intercondylar Width, Mandible Length and Intermolar Width measures consistently declined after IH insults in 3- and 4-week-old male as well as female animals. Three-week-old male IH-pups only showed a significantly reduced (p < 0.05) body weight compared to those of 3-week controls. However, female IH-pups were heavier than age-matched controls at all 3 time-points. Trabecular bone configuration, size of facial bones, and metabolism are disturbed after an IH challenge 1 h immediately after birth. The findings raise the possibility that IH, introduced by breathing patterns such as PB or AOP, induce significantly impaired bone development and metabolic changes in human newborns. The enhanced NE outflow from IH exposure may serve a major role in deficient bone growth, and may affect bone and other tissue influenced by that elevation.

Gestational intermittent hypoxia reduces mandibular growth with decreased Sox9 expression and increased Hif1a expression in male offspring rats

“…A previous study in a rat gestational IH model focused on the different negative effects between male and female offspring ( Wilson et al, 2022 ), which indicated that exposure to IH during pregnancy can mediate the developmental programming of both cortical and subcortical pathways, resulting in long-term negative consequences for male offspring compared with female offspring. Pae et al, 2011 ; Pae and Harper, 2023 ) revealed that IH exposure for 1 h immediately after birth causes higher nor-epinephrine levels in the blood and disturbance of mandibular bone remodeling for at least the first five postnatal weeks in male neonatal rats, in contrast to female pups. They also suggested that both bone deficiencies and potential metabolic alterations are sex-specific.…”