Delayed Maturation of Fetal Lung in Yellow KK Mice

Abstract

Yellow KK mice have the Ay allele and spontaneously develop non-insulin dependent diabetes mellitus (NIDDM). In the present study, female yellow KK mice were mated at 7 or 13 weeks of age (the average blood glucose levels were ca. 260 and 500 mg/dl, respectively), and their fetuses were examined on days 18 or 19 of gestation. The fetuses from 13-wk-old dams were smaller than those from 7-wk-old dams. The average lung weight on day 19 of gestation was slightly greater in the fetuses from 13-wk-old dams than in those from 7-wk-old dams (23.3 vs 21.2 mg). Histologically, alveolar spaces were smaller and alveolar walls were thicker in the fetuses from 13-wk-old dams than in those from 7-wk-old dams. Morphometric analysis revealed that the percentage area of the fetal lung occupied by alveolar spaces was significantly smaller in the former fetuses than in the latter. Day-15 fetal lungs of KK mice, which do not have the Ay allele, were cultured in hyperglycemic media (glucose levels: 400 and 700 mg/dl) for 48 hr. The development of alveoli was inhibited in hyperglycemic media as compared to the development of the lungs grown in the control medium. The inhibitory effect was dependent on the glucose concentration in the media. Thus, it seems that maternal hyperglycemia itself is a major cause of the delayed maturation of the fetal lung in NIDDM mice.