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The cellular basis of hypoxia induced craniofacial malformations
Author(s) -
Smith Francis Joel,
Marcucio Ralph S,
Hu Diane,
Hallgrimsson Benedikt
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.307.6
Subject(s) - craniofacial , hypoxia (environmental) , chemistry , biology , genetics , oxygen , organic chemistry
Craniofacial anomalies can arise from genetic and/or environmental factors, including prenatal hypoxia. Recent clinical evidence correlates hypoxia to craniofacial malformations. We examined the cellular mechanisms underlying malformations induced by hypoxia. Chicken eggs were incubated in hypoxia (9%, 11%, or 13% O2) or normoxia (21% O2). Embryos (days 3 to 6) were photographed for morphological analysis. Early stage embryos (2 days) were analyzed for apoptosis via whole‐mount TUNEL staining. Later stage embryos (days 4 and 6) were sectioned in paraffin for analysis of cell proliferation (BrdU) and apoptosis (TUNEL). Quantitative analysis of facial shape variation was performed on images of embryos via geometric morphometrics. Hypoxia disrupted cell proliferation, and in early stage embryos, caused apoptosis of neural crest progenitor cells. Hypoxic embryos displayed a spectrum of craniofacial anomalies, from mild asymmetry and eye defects to more severe frontonasal and cephalic anomalies. Morphometrics showed significant abnormal facial shape variation in relation to centroid size and age among individuals in hypoxic groups and between hypoxic groups versus the normoxic population. Further work will explore effects of hypoxia on molecular signaling in development. Grant Funding Source : NIH/NIDCR R01 ‐ DE018234