Effect of epidermal growth factor and dexamethasone on fetal rat lung development.
BACKGROUND
Epidermal growth factor (EGF), a mitogenic polypeptide that binds to cell surface receptors, is an important regulator of cell differentiation and fetal lung surfactant synthesis. We investigated the preventive and therapeutic effects of EGF in respiratory distress syndrome, by administering EGF and dexamethasone (Dex) to mother rat before delivery.


METHODS
Six female Sprague-Dawley (SD) rats were assigned to three groups (2 rats each); EGF or Dex was given to pregnant rats (EGF group and Dex group, respectively) from gestational day 16 to day 18 by intraperitoneal injection, while the group with normal saline injection was used as negative controls. Fetal rats were taken out of womb by hysterotomy on day 19 of pregnancy, then 24 fetal rats were randomly chosen from each group. Their body weights were measured, and pulmonary surfactant protein-A and -B (SP-A and SP-B) antigens were determined by immunohistochemical staining in each group. The histologic structure was examined under a light microscope, a light microscopic image system or an electron microscope.


RESULTS
The expressions of SP-A and SP-B could be detected in each group. A significant difference was observed for SP-A and SP-B in the EGF and Dex groups compared with the control group (P < 0.01). Image analysis showed that the relative values of air space area and interalveolar septa area in the EGF and Dex groups were significantly greater than those in the control group (P < 0.01), while no significant difference was found between the two groups (P > 0.05). The ultrastructural features of fetal lungs showed that the number of alveolar type II cells containing lamellar bodies in the EGF and Dex groups was apparently increased compared with that in the control group. The mean body weight of fetus from the Dex group was smaller than that from the control group ((1.3192 +/- 0.0533) g, (1.3863 +/- 0.0373) g), but there was no significant difference between the EGF group and the control group ((1.3986 +/- 0.0730) g, (1.3863 +/- 0.0373) g).


CONCLUSIONS
Maternal treatment with EGF and Dex on days 16 - 18 of gestation could promote morphogenesis and increase the surfactant levels in premature fetal lung. However, maternal treatment with Dex, not EGF, decreased the body weight.
Ma
Lian
L
Department of Pediatrics, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China.
Wang
Ai-hong
AH
Frieda
Law
L
He
Hong-yan
HY
Ma
Gui-xia
GX
Wang
Hong-wu
HW
Lin
Li-min
LM
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects* / Q000196:embryology* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D011247:Pregnancy; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D037701:Pulmonary Surfactant-Associated Protein B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; D004815:Epidermal Growth Factor; D003907:Dexamethasone