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ORIGINAL RESEARCH ARTICLE

Experimental Oligohydramnios Decreases Collagen in Hypoplastic Fetal Rat Lungs

Chung-Ming Chen^*,1, Hsiu-Chu Chou, Leng-Fang Wang and Yaw-Dong Lang

^* Department of Pediatrics, Department of Anatomy, Department of Biochemistry, and Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan

To whom requests for reprints should be addressed at ¹ Department of Pediatrics, College of Medicine, Taipei Medical University, Taipei 110, Taiwan. E-mail: cmchen{at}tmu.edu.tw

Neonates with premature rupture of the membrane and oligohydramnios have an increased risk of acute respiratory morbidity. The aims of this study are to investigate the effects of experimental oligohydramnios on transforming growth factor (TGF)-β1 and connective tissue growth factor (CTGF) expressions and collagen level in fetal rat lungs. On day 16 of gestation, we anesthetized timed pregnant Sprague-Dawley dams, punctured the uterine wall and fetal membranes of each amniotic sac which resulted in oligohydramnios. Fetuses in the opposite uterine horn served as controls. On days 19 and 21 of gestation, fetuses were delivered by cesarean section. Rats exposed to oligohydramnios exhibited significantly lower lung weight/body weight ratios on days 19 and 21 of gestation than did the control rats. Lung type I collagen and TGF-β1 mRNA expressions and lung collagen levels were significantly decreased in rats exposed to oligohydramnios on days 19 and 21 of gestation. Type I collagen and inhibitors of metalloproteinase-1 (TIMP-1) proteins were decreased and matrix metalloproteinase-1 (MMP-1) was increased in oligohydramnios-exposed rats on days 19 and 21 of gestation. CTGF mRNA expressions were comparable between control and oligohydramnios-exposed rats on days 19 and 21 of gestation. These data suggest that downregulation of collagen might be involved in the pathogenesis of oligohydramnios-induced respiratory morbidity.

Key Words: collagen • connective tissue growth factor • transforming growth factor