Retinoic acid fails to reverse oligohydramnios-induced pulmonary hypoplasia in fetal rats.
All-trans retinoic acid (ATRA) stimulates platelet-derived growth factor (PDGF)-A expression and enhances alveolarization in rat lungs. On d 16 of gestation, pregnant Sprague-Dawley rats were randomly assigned to either a retinoic acid group (intragastric ATRA at 10 mg/kg body weight) or a vehicle group. We punctured each amniotic sac, and fetuses in the opposite uterine horn served as controls. On d 21 of gestation, the fetuses were delivered by cesarean section. Rats subjected to oligohydramnios exhibited significantly lower lung weights and lung/body weight ratios, and ATRA had no effects on the body or lung weights of oligohydramnios-exposed rats. Lung PDGF-A and -B mRNA expression was significantly lower in oligohydramnios-exposed rats compared with control littermates of maternal vehicle-treated dams. Maternal retinoic acid treatment significantly increased PDGF-A and -B mRNA expression in control and oligohydramnios-exposed rats compared with all rats and oligohydramnios-exposed rats of maternal vehicle-treated dams, respectively. Rats exposed to oligohydramnios exhibited a significantly lower generation of alveolar saccules than did control rats in the maternal retinoic acid- and vehicle-treated groups. In this model, maternal retinoic acid treatment showed no positive effects on oligohydramnios-induced pulmonary hypoplasia in the pseudoglandular stage.
Chen
Chung-Ming
CM
Department of Pediatrics, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. cmchen@tmu.edu.tw
Chou
Hsiu-Chu
HC
Wang
Leng-Fang
LF
Lang
Yaw-Dong
YD
Yeh
Ching-Ying
CY
D000650:Amnion / Q000601:surgery; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005325:Fetal Organ Maturity / Q000187:drug effects*; D005865:Gestational Age; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000188:drug therapy* / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D016104:Oligohydramnios / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000196:embryology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014212:Tretinoin / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; C075278:platelet-derived growth factor A; D014212:Tretinoin