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Neonatal Lung Disease: Mechanisms Driving Sex Differences

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Sex-Based Differences in Lung Physiology

Part of the book series: Physiology in Health and Disease ((PIHD))

Abstract

The newborn lung exhibits many sex-specific differences during development, post-natal transition, and in the manifestation of neonatal lung diseases. These differences are evident during fetal lung development and are mainly related to maturity in surfactant production. The male sex disadvantage is prominently manifested in premature neonates, in whom many morbidities are skewed toward the male sex. Respiratory distress syndrome and bronchopulmonary dysplasia (BPD) show a higher incidence in premature boys. Despite the well-established sex-specific differences in the incidence of BPD and impaired lung function in males, the molecular mechanism(s) behind them are not completely understood. The recovery in lung function following neonatal lung injury in infants with BPD is better in females. Differential modulation of genes related to inflammation, antioxidant pathways, and sex-chromosome-associated genes and epigenetic pathways including miRNAs may play a role in this sexual dimorphism. Cellular sex also plays a role in dictating the cell fate under stress and sex-based differences have been reported in lung endothelial cells and fibroblasts. The neonatal lung may thus be modulated by hormone-dependent and -independent mechanisms that lead to sex differences both at baseline and after injury exposure.

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  1. Krithika Lingappan and Brielle Hayward-Piatkovskyi contributed equally with all other contributors.

Authors and Affiliations

  1. Department of Pediatrics, Section of Neonatology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, USA

    Krithika Lingappan

  2. Department of Biological Sciences, University of Delaware, Delaware, USA

    Brielle Hayward-Piatkovskyi

  3. Department of Biological Sciences, and Department of Biomedical Engineering, University of Delaware, Delaware, USA

    Jason P. Gleghorn

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  1. Krithika Lingappan
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Correspondence to Krithika Lingappan .

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  1. Department of Environmental and Occupational Health, Indiana University Bloomington, School of Public Health, Bloomington, IN, USA

    Patricia Silveyra

  2. Office of Research on Women’s Health, Office of the Director, National Institutes of Health Bethesda, Bethesda, MD, USA

    Xenia T. Tigno

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Lingappan, K., Hayward-Piatkovskyi, B., Gleghorn, J.P. (2021). Neonatal Lung Disease: Mechanisms Driving Sex Differences. In: Silveyra, P., Tigno, X.T. (eds) Sex-Based Differences in Lung Physiology. Physiology in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-63549-7_5

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