Abstract

Our research is exploiting the marsupial as a model to understand the signals required for lung development. Marsupials have a unique reproductive strategy, the mother gives birth to altricial neonate with an immature lung and the changes in milk composition during lactation in marsupials appears to provide bioactives that can regulate diverse aspects of lung development, including branching morphogenesis, cell proliferation and cell differentiation. These effects are seen with milk collected between 25 and 100 days postpartum. To better understand the temporal effects of milk composition on postnatal lung development we used a cross-fostering technique to restrict the tammar pouch young to milk composition not extending beyond day 25 for 45 days of its early postnatal life. These particular time points were selected as our previous study showed that milk protein collected prior to ~ day 25 had no developmental effect on mouse embryonic lungs in culture. The comparative analysis of the foster group and control young at day 45 postpartum demonstrated that foster pouch young had significantly reduced lung size. The lungs in fostered young were comprised of large intermediate tissue, had a reduced size of airway lumen and a higher percentage of parenchymal tissue. In addition, expression of marker genes for lung development (BMP4, WNT11, AQP-4, HOPX and SPB) were significantly reduced in lungs from fostered young. Further, to identify the potential bioactive expressed by mammary gland that may have developmental effect on pouch young lungs, we performed proteomics analysis on tammar milk through mass-spectrometry and listed the potential bioactives (PDGF, IGFBP5, IGFBPL1 and EGFL6) secreted in milk that may be involved in regulating pouch young lung development. The data suggest that postnatal lung development in the tammar young is most likely regulated by maternal signalling factors supplied through milk.

Highlights

  • In mammals the lung has evolved as a respiratory organ to exchange gases immediately after birth (Philip, 1977)

  • Studies in marsupial species including the Julia Creek dunnart (Sminthopsis douglasi) (Frappell and Mortola, 2000), tammar wallaby (Macropus eugenii) and gray short tailed opossum (Monodelphis domestica) (Szdzuy et al, 2008) have shown the lungs of newborns are comprised of a small number of large air sacs providing insignificant surface area for respiration, and the lungs are considered as functionally immature (Mess and Ferner, 2010)

  • Tammar lactation is potentially programmed to regulate the developmental changes in pouch young

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Summary

Introduction

In mammals the lung has evolved as a respiratory organ to exchange gases immediately after birth (Philip, 1977). Studies in marsupial species including the Julia Creek dunnart (Sminthopsis douglasi) (Frappell and Mortola, 2000), tammar wallaby (Macropus eugenii) and gray short tailed opossum (Monodelphis domestica) (Szdzuy et al, 2008) have shown the lungs of newborns are comprised of a small number of large air sacs providing insignificant surface area for respiration, and the lungs are considered as functionally immature (Mess and Ferner, 2010) These marsupial newborn have adopted a unique respiratory mechanism to perform partial gaseous exchange through skin during early postnatal development to meet their oxygen demand (Frappell and Mortola, 2000; Mortola et al, 1999). This regime examined the hypothesis of temporal effects of milk composition on lung development

Cross-fostering the PYs to control the milk composition
Lung morphology of PY in foster and control groups
Discussion
Cross-fostering
Morphological analysis of embryonic lung
Total RNA isolation and quantitative RT-PCR
Milk collection and analysis
Mass-spectrometry
Functional categorisation
Full Text
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