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. Author manuscript; available in PMC: 2014 Oct 3.
Published in final edited form as: Expert Rev Respir Med. 2013 Oct 3;7(5):515–531. doi: 10.1586/17476348.2013.838020

Table 1. Key Effects of Detrimental Prenatal and Postnatal Factors in Lung Development.

Data derived from multiple references. See text for details and individual references from bibliography.

Model Key Findings Mechanisms
Prenatal Factors Intra-amniotic,-uterine, - peritoneal endotoxin
  • ↓ Alveolarization

  • ↑ Surfactant

  • ↓ Gas exchange

  • Altered angiogenesis

  • ↑ TNF-α, IL-1β, and IL-8

  • ↓ Caveolin-1 expression

  • ↑ TGF-β expression and signaling

  • ↑ MMP expression

  • Altered FGF signaling

Intrauterine growth restriction
  • ↓ Alveolarization and vascularization

  • ↓ Surfactant

  • ↓ Gas exchange

  • Altered ECM composition

  • ↓ Surfactant protein mRNA

  • ↓ Vascular endothelial growth factor

  • (VEGF) and VEGFR expression

Maternal smoking
  • ↓ Alveolarization

  • ↑ AHR

  • ↑ ASM thickness

  • ↑ TGF-β

  • ↑ Procollagen I and III mRNA expression

  • ↑ Th2 cytokine responses

  • Altered Wnt signaling

Maternal Diabetes
  • ↓ Alveolar type II cell differentiation

  • ↓ Surfactant

  • ↑ Oxidative stress

  • ↑ Collagen I and III expression

  • ↑ MMP expression

  • ↓ Phosphatidylcholine levels

Pollution
  • ↑ Airway inflammation

  • ↑ AHR

  • ↑ Mucus secretion

  • ↑ TNF-α, IL-1β, KC, MCP-1

  • ↑ Th2 cytokine responses

Postnatal Factors Respiratory Support
  • ↓ Alveolarization

  • ↑ AHR

  • ↑ ASM thickness

  • ↑ ASM proliferation

  • ↑ ECM remodeling

  • ↓ Airway relaxation

  • ↑ TNF-α, IL-1β, IL-6, and IL-8

  • ↑ TGF-β expression and activity

  • ↑ MMP/TIMP expression

  • ↑ BDNF expression

  • ↑ Myosin regulatory light chain

  • phosphorylation

  • ↓ cAMP and PGE2 levels

Respiratory Infection
  • ↑ Airway inflammation

  • ↑ Mucus secretion

  • ↑ AHR

  • ↑ IL-13 and TNF-α

  • ↑ Th2 responses mediated by IL-4Rα

Allergens
  • ↑ AHR

  • ↑ ECM remodeling

  • ↑ IL-4/IL-13 expression

  • ↑ Mucus production

Pollution
  • ↑ AHR

  • ↑ Epithelial-mesenchymal transition of airway epithelial cells

  • Altered distal airway structure

  • ↑ Oxidative stress

  • ↓ Activity of glutathione-dependent detoxifying enzyme