Abstract
Within this review, sex-specific differences in alveolar epithelial functions are discussed with special focus on preterm infants and the respiratory disorders associated with premature birth. First, a short overview about fetal lung development, the challenges the lung faces during perinatal lung transition to air breathing and respiratory distress in preterm infants is given. Next, clinical observations concerning sex-specific differences in pulmonary morbidity of human preterm infants are noted. The second part discusses potential sex-specific causes of pulmonary complications, including pulmonary steroid receptors and local lung steroid metabolism. With regard to pulmonary steroid metabolism, it is important to highlight which steroidogenic enzymes are expressed at which stage during fetal lung development. Thereafter, we review the knowledge concerning sex-specific aspects of lung growth and maturation. Special focus is given to alveolar epithelial Na+ transport as a driver of perinatal lung transition and the sex differences that were noted in this process.
Highlights
Therein, two separate consecutive phases can be identified, lung growth representing the structural development and lung maturation which refers to the functional development
Besides differences in alveolar structure between male and female fetal lungs, fetal lung maturation differs in several aspects
Differences in the onset of surfactant synthesis were corroborated by alterations of the epithelial-mesenchymal relationship, possibly mediated by sex steroids
Summary
Fetal lung development is a highly coordinated process of branching morphogenesis, angiogenesis, and alveolarization that continues postnatally [1]. Branching morphogenesis antagonizes alveolar maturation as shown in the mouse lung [3]. In addition to the phases of growth and maturation, lung development is further divided into five stages. Conducting epithelial tubes are formed by progressive airway branching in the pseudoglandular stage starting at about 5 weeks of human gestation. The saccular stage covers the period from 26 weeks until near term. During this stage, most peripheral airways form widened airspaces, termed sacculi, coated with alveolar type I (ATI) and type II (ATII) cells. This alveolarization and therein the formation of secondary septa constitutes the alveolar stage which continues postnatally
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