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Intrauterine fetal constraint induces chondrocyte apoptosis and premature ossification of the cranial base.

Abstract：

BACKGROUND:The spheno-occipital synchondrosis is an important growth center of the craniofacial skeleton and a primary site of malformation in syndromic forms of craniosynostosis. Clinical and laboratory investigations have demonstrated that premature closure of cranial vault sutures in nonsyndromic craniosynostosis is associated with characteristic alterations in cranial base morphology. However, a causal link between premature fusion of calvarial sutures and changes in the cranial base remains elusive. The purpose of these experiments was to test the hypothesis that intrauterine head constraint produces ultrastructural changes in the spheno-occipital synchondroses of fetal mice. METHODS:Fetal constraint was induced through uterine cerclage of six pregnant C57Bl/6 mice on the eighteenth day of gestation. Fetuses were harvested after growing to 24, 48, and 72 hours beyond the normal 20-day gestational period. Between six and nine fetuses were harvested at all time points in both treatment and control groups. The morphology and cell biology of the spheno-occipital synchondroses, in constrained fetuses and unconstrained controls, were examined using hematoxylin and eosin-stained sections. Chondrocyte apoptosis was examined using terminal deoxynucleotidyl transferase-mediated dUDP end-labeling assays and electron microscopy. RESULTS:In nonconstrained animals, the spheno-occipital synchondrosis demonstrated normal architecture and normal chondrocyte morphology at all time points. In contrast, intrauterine constraint resulted in a progressive disruption of the normal cellular architecture of the spheno-occipital synchondrosis over 72 hours, with premature ossification of the synchondrosis. Widespread chondrocyte apoptosis within the synchondrosial growth center was demonstrated by terminal deoxynucleotidyl transferase-mediated dUDP end-labeling assays and electron microscopy. CONCLUSION:These experiments confirm the ability of intrauterine constraint to induce changes in the morphology and cell biology of the cranial base in synostotic fetuses.

journal_name

Plast Reconstr Surg

journal_title

Plastic and reconstructive surgery

authors

Smartt JM Jr,Karmacharya J,Gannon FH,Teixeira C,Mansfield K,Hunenko O,Shapiro IM,Kirschner RE

doi

10.1097/01.prs.0000182224.98761.cf

subject

Has Abstract

pub_date

2005-10-01 00:00:00

pages

1363-9

issue

eissn

0032-1052

issn

1529-4242

pii

00006534-200510000-00024

journal_volume

116

pub_type

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Intrauterine fetal constraint induces chondrocyte apoptosis and premature ossification of the cranial base.