Immature alveolar/blood barrier and low disaturated phosphatidylcholine in fetal lung after intrauterine exposure to O,O,S-trimethylphosphorothioate.
Intrauterine exposure to the potent lung toxicant OOS-TMP was found to result in neonatal lethality attributed to immature lungs (Koizumi et al. 1988). The present study was initiated to investigate biological/pathological profiles of such pulmonary immaturity. OOS-TMP was given p.o. to five pregnant female Sprague-Dawley rats on gestation day (G) 19 at 2.5, 7 or 20 mg/kg. Control (N = 6) or pair-fed dams (N = 5: pair-fed to 20 mg/kg dams) received 2 ml/kg corn oil. On G 22, fetuses were delivered by Cesarean section. The biochemical maturity of lungs was assessed by glycogen content and production of disaturated phosphatidylcholine (DSPC), a major component of pulmonary surfactant. Mean DSPC content was significantly lower in fetuses from dams dosed at 7 or 20 mg/kg while mean glycogen concentration, in contrast, was 3- to 6-fold higher in those fetuses than fetuses from control or pair-fed dams. Pathological examination revealed that in fetuses delivered from dams dosed at 7 mg/kg or 20 mg/kg, glycogen-rich cuboidal epithelial cells completely covered the terminal air space and alveolar/blood barriers stayed at the poorly developed stage. The stage of the pulmonary development in those fetuses was similar to those in fetuses on G19. Therefore it was concluded that intrauterine exposure to OOS-TMP delayed pulmonary development, thereby causing respiratory failure after birth.
Koizumi
A
A
Department of Hygiene, Akita University School of Medicine, Japan.
Sageshima
M
M
Wada
Y
Y
Narita
S
S
Higuchi
S
S
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D008297:Male; D063086:Organothiophosphates / Q000633:toxicity*; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D010713:Phosphatidylcholines / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; D010713:Phosphatidylcholines; C019123:O,O,S-trimethyl phosphorothioate