The adrenal cortex in experimental congenital diaphragmatic hernia.
OBJECTIVE
Adrenal cortical malfunction was found recently in patients with severe congenital diaphragmatic hernia (CDH). The current study tests the hypothesis that the development and function of the adrenal cortex could be abnormal in an experimental model of CDH.


METHODS
Pregnant rats were exposed on day 9.5 of gestation to 100 mg of 2-4-dichlorophenyl-p-nitrophenyl ether (nitrofen) diluted in olive oil. The sham group was treated only with oil. Fetuses were recovered on the 21st day, bled, and examined for the presence or absence of CDH. Adrenal glands from sham and CDH animals were dissected, weighed, and prepared for histologic, biochemical, and immunohistochemical studies (ki-67) aimed at measuring total DNA, total protein, and the proportion of proliferating cells. Serum corticosterone levels were assayed. The results in both groups were compared with parametric tests with a significance level of P <.05.


RESULTS
The adrenal weight was not different in CDH animals versus controls (0.049 +/- 0.014 v 0.052 +/- 0.012% of body weight; not significant). Total DNA was reduced significantly (1.180 +/- 0.481 v 1.909 +/- 0.893 microgram P <.05) with unchanged DNA to protein ratio. Proliferation index in both groups was 20.1 +/- 3.1% and 26.5 +/- 7.5%, respectively (not significant), and the proliferating cells were mainly located in the glomerular areas of the glands. Corticosterone levels were similar in both groups.


CONCLUSIONS
Nitrofen induces very slight changes in the development of adrenal glands of fetal rats, expressed by reduced cell proliferation especially in glomerular areas, reduced total DNA with preservation of cell sizes (constant DNA to protein ratio), with no change in function because corticosterone levels remained unchanged. It is doubtful that primary adrenal malformation/malfunction contributes to the severity of CDH in this model.
Department of Pediatric Surgery, Biochemistry Laboratory, and Pathology, Hospital Universitario "La Paz," Madrid, Spain.
M J
MJ
Rodriguez-Matas
S
S
Gonzalez-Reyes
L
L
Martínez
I
I
Martínez
J I
JI
Rodriguez
J A
JA
Diez-Pardo
J A
JA
Tovar
D000302:Adrenal Cortex / Q000002:abnormalities* / Q000187:drug effects / Q000473:pathology; D000311:Adrenal Glands / Q000473:pathology; D000818:Animals; D003345:Corticosterone / Q000097:blood; D004247:DNA / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000473:pathology; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000473:pathology; D065630:Hernias, Diaphragmatic, Congenital; D009929:Organ Size; D010647:Phenyl Ethers; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D010647:Phenyl Ethers; D004247:DNA; C007350:nitrofen; D003345:Corticosterone