title: The induction of congenital spinal deformities in mice by maternal carbon monoxide exposure.
abstract: Carbon monoxide (CO) has been shown to be teratogenic in mice. High altitude hypoxia has also been shown to induce congenital vertebral anomalies in mice. The purpose of this study was to investigate the effect of maternal hypoxia owing to CO exposure and the production of congenital spinal deformities in the offspring. Sixty DBA-1J mice were bred using polygamous timed breeding methods. Pregnant females were exposed to 200, 400, or 600 ppm CO using a custom-designed gas blender system. Seven-hour exposures were performed on day 8.5, 9.5, or 10.5 of the 21-day gestation cycle. The neonates were euthanized at birth; the specimens were fixed, eviscerated, and radiographed. Congenital spinal deformities were observed (wedge, hemi, fused, and missing vertebrae; fused ribs) and were located in all regions of the spine. There was a statistically significant difference in the number of spinal deformities between all groups, with no defects in the controls and a 77% incidence at 600 ppm (p < 0.0001). There was no apparent correlation between the time of exposure and defect location. The most sensitive time of gestation was 9.5 days. We identified an animal model of congenital spinal deformities that compares favorably with the evidence of human congenital spinal deformities in cases of maternal exposure to CO and other gas and chemical fumes.
authors.affiliation: Section of Orthopaedic Surgery, School of Medicine, School of Public Health, University of Michigan, Ann Arbor, USA. rloder@shrinenet.org
authors.forename: R T
authors.initials: RT
authors.lastname: Loder
authors.forename: M J
authors.initials: MJ
authors.lastname: Hernandez
authors.forename: A L
authors.initials: AL
authors.lastname: Lerner
authors.forename: D J
authors.initials: DJ
authors.lastname: Winebrener
authors.forename: S A
authors.initials: SA
authors.lastname: Goldstein
authors.forename: R N
authors.initials: RN
authors.lastname: Hensinger
authors.forename: C Y
authors.initials: CY
authors.lastname: Liu
authors.forename: M A
authors.initials: MA
authors.lastname: Schork
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000633:toxicity*; D003627:Data Interpretation, Statistical; D005260:Female; D005865:Gestational Age; D006801:Humans; D000860:Hypoxia / Q000150:complications; D018811:Maternal Exposure; D051379:Mice; D008811:Mice, Inbred DBA; D009139:Musculoskeletal Abnormalities / Q000139:chemically induced* / Q000000981:diagnostic imaging; D011247:Pregnancy; D011248:Pregnancy Complications; D011859:Radiography; D013131:Spine / Q000002:abnormalities* / Q000000981:diagnostic imaging; D013997:Time Factors
chemical_list: D002248:Carbon Monoxide