Figures
- Fig. 1.—
Inhibition of endogenous retinoic acid synthesis disrupts normal alveolar formation. a) Representative photomicrograph of a normal P23 mouse lung showing typical alveolar architecture. b) Disulphiram-treated P23 lung at the same magnification as a) showing fewer, larger airspaces with thicker alveolar walls consistent with an immature appearance. Scale bars=50 µm. c) Calculation of the average distance between alveolar walls (Lm) demonstrates that disulphiram treatment during alveologenesis (n=6) significantly increased (p<0.01) Lm compared with controls (n=7) at P23.
- Fig. 2.—
Increasing concentrations of dexamethasone (Dex) decreases alveolar number and increases mean chord length (Lm). Histological appearance of the lungs at P30 in a) control mice, b) 0.05 µg Dex-treated mice, c) 0.2 µg Dex-treated mice, and d) 0.4 µg Dex-treated mice. e) Lm measurements of the treatment groups. There is no significant difference between controls and 0.05 µg Dex, but there is a significant difference (p<0.02) between controls and 0.2 µg Dex, and controls and 0.4 µg Dex. Scale bars=50 µm.
- Fig. 3.—
Increasing the duration of dexamethasone (Dex) dosing decreases alveolar number and increases mean chord length (Lm). Scale bars=50 µm Histological appearance of lungs at P30 in a) control mice, and in mice treated with 0.4 mg·kg−1 Dex for b) 3days, c) 5 days and d) 10 days. e) Lm measurements of the treatment groups. Dex dosing for 5 and 10 days resulted in a significantly increased Lm at P30. There is no significant difference in Lm between controls and 3 days of Dex. ***: p<0.001 versus control.
- Fig. 4.—
Effects of dexamethasone (Dex) on somatic growth and long-term lung structure. a) 10 days of Dex (0.4 mg·kg−1) has an obvious developmental delay in the experimental animal (left) compared with its sibling control (right) at P15. b) By P25 there has been a catch-up of somatic growth such that the experimental animal (to the rear) is now only marginally smaller than its sibling control (to the front). c) Control P150 lung. d) Dex-treated lung at P150. Scale bars=50 µm.
- Fig. 5.—
a) High performance liquid chromatography analysis of lung all-trans-retinol (□) and all-trans-retinoic acid (RA; └) following a single intraperitoneal dose of all-trans‐RA. RA arrives in the lung within 5 min and there is a peak within 15 min. This falls to near undetectable levels within 4 h. There is no significant change in retinol levels. The structure of the lung at P90 is shown in b) control lung, c) dexamethasone (Dex)‐treated lung, which results in fewer larger alveoli and d) RA‐treated lung, which rescues the disrupted phenotype and restores the alveolar structure and number. Scale bars=50 µm. e) Body weights of the animals at P90. Dex dosing (Dex/oil) results in a significant reduction in body mass and RA treatment (Dex/RA) has no significant effect on body weight. f) Lung volumes at P90. There is no significant difference in lung volume between the three groups. g) Mean chord length (Lm) at P90. Dex treatment results in a significantly increased Lm compared with controls (phosphate-buffered saline (PBS)/oil). RA treatment results in a significant reduction in Lm (p<0.01) compared with Dex towards that of the control animals. h) Surface area (SA) of lung per 100 g body weight at P90. Dex dosing results in significantly reduced SA per 100 g compared with controls. RA restores the SA per 100 g such that there is no significant difference between the RA group and the control group. **: p<0.01 versus control; ***: p<0.001 versus control; #: p<0.01 versus Dex.
Tables
- Table 1
Data on sex, weight, lung volume (LV) and mean chord length (Lm) for the effect of dexamethasone (Dex) followed by retinoic acid (RA)
Group Sex n Weight g LV cm2 LV/weight cm3·g−1 Lm µm SA cm3 Normalised SA to weight cm2·100 g−1 PBS/oil M 6 40.9±1.2 0.938±0.01 0.022 74.85±1.39 501.3 122.57 F 2 29.7±12.8 0.833±10.06 0.028 68.06±3.27 489.5 164.81 Dex only M 3 29.9±1.82 0.958±0.01 0.032 127.77±5.97 299.9 100.34 F 4 26.9±1.60 0.897±0.01 0.033 104/43±5.24 343.6 127.73 Dex/RA M 6 31.98±0.55 0.987±0.02 0.031 88.89±4.46 444.1 138.87 F 4 25.62±0.62 0.911±0.03 0.035 84.113±6.94 433.2 169.13 -
SA: surface area
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PBS: phosphate-buffered saline
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