title: Fetal hyperglycemia alters lung structural development in neonatal rat.
abstract: Maternal diabetes is associated with increased risk for abnormal fetal organogenesis, but its effects on the developing lungs are still insufficiently known. To determine the effect of maternal hyperglycemia on postnatal lung development, we studied lung structural and cellular changes in newborn rats exposed to intrauterine hyperglycemia. We induced hyperglycemia in Sprague-Dawley rats with i.p. streptozotocin before pregnancy and allowed the hyperglycemic and control dams deliver at term. Lungs were obtained on postnatal day (d) 0, d7, and d14 and analyzed for lung weight and morphology, as well as cellular apoptosis (TUNEL staining) and proliferation (PCNA staining). Quantitative micro-CT analysis of the lung vasculature was additionally performed at d14. At birth, maternal hyperglycemia resulted in decreased relative lung weight, thinner alveolar septa and increased cellular apoptosis and proliferation, when compared to controls. At 1 and 2 weeks of age pulmonary cell apoptosis and alveolar chord length remained unchanged, but cell proliferation and number of secondary crests were increased in the hyperglycemia-exposed neonatal lungs in comparison with the controls. Density of small arterioles on histological examination and the structure of pulmonary arterial vasculature in micro-CT analysis of the neonatal lungs were not influenced by maternal hyperglycemia. Our results suggest, that maternal hyperglycemia is related to developmental structural alterations in postnatal rat lungs. These early changes may reflect aberrant maturational adaptation in response to the hyperglycemic fetal environment.
authors: The Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland. anviar@utu.fi
authors: Anna
authors: A
authors: Koskinen
authors: Heikki
authors: H
authors: Lukkarinen
authors: Niko
authors: N
authors: Moritz
authors: Heikki
authors: H
authors: Aho
authors: Pekka
authors: P
authors: Kääpä
authors: Hanna
authors: H
authors: Soukka
mesh_terms: D000792:Angiography; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D016640:Diabetes, Gestational / Q000473:pathology*; D005260:Female; D047109:Fetal Development; D005333:Fetus / Q000000981:diagnostic imaging / Q000473:pathology; D006943:Hyperglycemia / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000000981:diagnostic imaging / Q000254:growth & development* / Q000473:pathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D018809:Proliferating Cell Nuclear Antigen; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018809:Proliferating Cell Nuclear Antigen