[Thyroid C cells are decreased in experimental CDH].
OBJECTIVE
Experimental CDH is often associated with malformations of neural crest origin. Several of these features are present in human CDH and therefore likely similar pathogenic mechanisms should be explored. The aim of the present study is to examine whether thyroid C-cells, another neural crest derivative, are abnormal in this rat model.


METHODS
Pregnant rats were exposed either to 100 mg of 2-4-dichlorophenyl-p-nitrophenyl ether (nitrofén) or vehicle (controls) on 9.5 day of gestation. Fetuses were recovered on day 21st and the thyroids of those with CDH (68%) were immuno-histochemically stained with anti-calcitonin antibody. The number of positively stained cells per high power field were counted using a computer-assisted image analysis method in at least 5 sections per thyroid. The distribution of the cells within the gland was assessed as well. Comparisons between CDH and control rats were made by non-parametric tests with a significance threshold of p<0.05.


RESULTS
The number of c-cells was dramatically reduced in CDH animals in comparison with controls (101.2 +/- 61.3 vs 23.1 +/- 37, p<0.0001). Histology of the thyroid was similar in both groups, but the distribution of positive C-cells within the gland followed an abnormal pattern in CDH rats with the cells tending to be located at the periphery rather than at the core of the lobes.


CONCLUSIONS
Nitrofén induces a severe decrease in thyroid C cells accompanied by abnormal distribution patterns. These results add further evidence of the involvement of a neural crest dysregulation as a component of the pathogenesis of experimental CDH. Whether there is or not a clinical counterpart to these findings is still unknown, but the nature of the cardiovascular and craneo-facial malformations in some babies with CDH strongly support further research in this field.
Martínez
L
L
Departamento de Cirugía Pediátrica, Hospital Universitario La Paz, Madrid. lmartinezm.hulp@saludm.madrid.org
De Ceano-Vivas
M
M
González-Reyes
S
S
Fernández-Dumont
V
V
Calonge
W M
WM
Ruiz
E
E
Rodríguez
J I
JI
Tovar
J A
JA
D000818:Animals; D005260:Female; D006548:Hernia, Diaphragmatic / Q000196:embryology / Q000453:epidemiology*; D065630:Hernias, Diaphragmatic, Congenital; D008297:Male; D009432:Neural Crest / Q000187:drug effects / Q000473:pathology; D010575:Pesticides / Q000009:adverse effects; D010647:Phenyl Ethers / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012107:Research Design; D013959:Thyroid Diseases / Q000139:chemically induced / Q000196:embryology / Q000473:pathology*; D013961:Thyroid Gland / Q000187:drug effects / Q000196:embryology / Q000473:pathology*
D010575:Pesticides; D010647:Phenyl Ethers; C007350:nitrofen