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Published on: November 2, 2015
Intermittent hypoxia in neonatal rodents affects facial bone growth
Eung-Kwon Pae1, Ronald M Harper2
1Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Maryland, Baltimore, MA, United States of America.
Insights
Intermittent hypoxia (IH) in newborns, caused by periodic breathing or apnea of prematurity, impairs facial bone development and metabolism. This is linked to increased norepinephrine levels, potentially affecting bone growth in infants.
Area of Science:
- Developmental biology
- Neonatal physiology
- Bone biology
Background:
- Preterm infants often experience periodic breathing (PB) or apnea of prematurity (AOP), leading to intermittent hypoxia (IH).
- The impact of transient IH on facial bone development in newborns is not fully understood.
Purpose of the Study:
- To investigate the cause-effect relationship between transient intermittent hypoxia and reduced facial bone growth in a neonatal rat model.
- To explore the role of norepinephrine in mediating these effects.
Main Methods:
- Neonatal Sprague-Dawley rat pups were exposed to IH (oxygen cycling 10-21% every 4 min for 1 hour post-birth) or control conditions.
- Body weight, facial bone dimensions (intercondylar width, mandible length, intermolar width), and serum norepinephrine levels were measured at 3, 4, and 5 weeks.
- Osteoclast activity and sympathetic nerve endings in sub-condylar regions were assessed.
Main Results:
- IH exposure led to increased osteoclast activity and sympathetic nerve endings in the sub-condylar region.
- Male IH-pups exhibited significantly higher norepinephrine levels at all time points.
- Facial bone dimensions were consistently reduced in IH-exposed animals, while body weight showed sex-specific differences.
- Trabecular bone configuration and metabolism were disturbed following IH exposure.
Conclusions:
- Transient intermittent hypoxia in early life significantly impairs facial bone development and alters metabolism.
- Enhanced norepinephrine outflow following IH exposure may play a crucial role in deficient bone growth.
- Findings suggest a potential mechanism linking breathing patterns in preterm infants to impaired bone development.
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.
