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Review
. 2015 Apr;93(2):119-27.
doi: 10.1139/bcb-2014-0093. Epub 2014 Oct 13.

Epigenetic contributions to the developmental origins of adult lung disease

Lisa A Joss-Moore  1 , Robert H Lane, Kurt H Albertine
Affiliations
Review

Epigenetic contributions to the developmental origins of adult lung disease

Lisa A Joss-Moore et al. Biochem Cell Biol. 2015 Apr.

Abstract

Perinatal insults, including intrauterine growth restriction, preterm birth, maternal exposure to toxins, or dietary deficiencies produce deviations in the epigenome of lung cells. Occurrence of perinatal insults often coincides with the final stages of lung development. The result of epigenome disruptions in response to perinatal insults during lung development may be long-term structural and functional impairment of the lung and development of lung disease. Understanding the contribution of epigenetic mechanisms to life-long lung disease following perinatal insults is the focus of the developmental origins of adult lung disease field. DNA methylation, histone modifications, and microRNA changes are all observed in various forms of lung disease. However, the perinatal contribution to such epigenetic mechanisms is poorly understood. Here we discuss the developmental origins of adult lung disease, the interplay between perinatal events, lung development and disease, and the role that epigenetic mechanisms play in connecting these events.

Keywords: developmental origins; développement pulmonaire; epigenetic; lung development; origines développementales; programmation; programming; épigénétique.

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Figures

Figure 1
Figure 1. Variance of lung function with age
Lung function, represented by FEV1 as a % of maximal value, varies with age and reaches a maximum in the early 20s. The solid line represents FEV1 variation with age under conditions of normal growth, and in the absence of disease or additional insults (e.g. smoking). The dashed line represents FEV1 in the case of reduced lung growth and/or development during early in life. Failure to achieve normal maximal lung function, even with normal age-related decline, produces respiratory symptoms (shaded area). The dotted line represents a more rapid decline in lung function as a result of additional insults (e.g. smoking), in which case respiratory symptoms are observed at earlier ages. Figure adapted from (Weiss, 2010, Stocks et al., 2013).
Figure 2
Figure 2. The impact of an injury stimulus to the immature lung
An injury stimulus to the immature lung may prompt an epigenetic response and subsequent cellular remodeling. The schematic shows cellular remodeling for the lamb lung mesenchyme in response to preterm birth with support by intermittent mandatory ventilation with oxygen-rich gas for 21days. Histopathological outcomes are shown in panels a–d. Panel a illustrates accumulation of smooth muscle cells surrounding a terminal bronchiole (TB) and its adjacent pulmonary arteriole (PA) compared to an age-matched term reference lamb (panel b). Panel c shows distended distal airspaces (DAS) with aberrant, excessive accumulation of mature cross-linked elastic fibers (black). This architecture is unlike the normal delicate, lacy features of an age-matched term reference lamb (panel d) with anatomic alveoli (A), thin walls and concentrated elastin at the tip of secondary septa.
Figure 3
Figure 3. Timeline of rat lung development
Representative images of female rat lungs at postnatal day 0 (P0), P6, P14 and P21. At P0, the rat lung is at the saccular stage of lung development. Alveolar formation takes place from approximately P4 to P14. At P21 alveoli have characteristic histological features of long, straight alveolar walls and numerous, long secondary septa. All panels original magnification 80 × (scale bar is 50 μm).
See this image and copyright information in PMC

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