Quantitative immunohistochemical analysis of the effect maternal hemoglobin levels on the pneumocyte area and vascularity of the developing human fetal lungs

Background The lungs are vulnerable to perinatal insults, genetic conditions, environmental and lifestyle factors. Maternal anemia affects a significant proportion of pregnant women in developing countries and has a deleterious influence on fetal development. Maternal anemia directly affects oxygen transfer, leading to chronic intrauterine hypoxia and placental insufficiency, which critically impacts the structural integrity and functioning of the fetal lungs. Methods An observational study was conducted on thirty-one pairs of lungs of stillborn or aborted fetuses between 12─36 weeks of gestation. Fetal lungs were processed, paraffin blocks made, sections of 3-μm thickness were prepared for immunohistochemistry (using primary antibodies targeting CD31 for vascular endothelium, Podoplanin for type I pneumocytes and Surfactant Protein-C for type II pneumocytes), and studied by light microscopy. Five random fields were photographed, and quantification was done using Fiji ImageJ2 software. Results A strong positive correlation (r = 0.679, p<0.01) existed between maternal hemoglobin concentration and type II pneumocyte cell area. Maternal anemia during canalicular and saccular-alveolar periods of lung maturation was associated with a statistically insignificant increase in type I pneumocyte cell area and lung vascular area. Conclusion This study demonstrated that prenatal hypoxia resulting from maternal anemia affects pulmonary vascularity and the differentiation of alveolar pneumocytes. Unlocking the molecular mechanisms that regulate normal lung development and the impact of its disruption will help our understanding of the origin of developmental lung disorders and chronic respiratory diseases in adults. This will allow researchers to design effective treatment modalities for better patient outcomes. MINI-ABSTRACT: Fetal hypoxia due to maternal anemia impacts pulmonary vascularity and differentiation of alveolar pneumocytes. This makes the lungs vulnerable to developmental lung diseases, and chronic respiratory disorders in later life.