Negative impact of hyperglycaemia on mouse alveolar development

Area of Science:

• Developmental Biology
• Endocrinology
• Pulmonology

Background:

• Diabetes mellitus during pregnancy is known to affect embryonic development.
• The impact of diabetes on embryonic respiratory system development remains controversial.

Purpose of the Study:

• To investigate the effects of pregestational diabetes mellitus (PGDM) on embryonic lung development in mice.
• To elucidate the molecular mechanisms underlying PGDM-induced lung abnormalities.

Main Methods:

• Utilized a mouse model of pregestational diabetes mellitus.
• Employed immunostaining, Western blotting, and Masson staining to assess lung morphology and molecular changes.
• Investigated the roles of Wnt and Fgf signaling pathways in high glucose-treated lung cells (MLE-12).

Main Results:

• PGDM led to significant morphological changes in embryonic lungs, including increased proliferation and decreased apoptosis.
• Hyperglycemia induced pulmonary tissue fibrosis, reduced type II pulmonary epithelial cell numbers, and altered cell differentiation.
• Activated Wnt and Fgf signaling pathways were implicated in suppressing GATA6 and pro-SPC expression and promoting fibrosis and epithelial-mesenchymal transition (EMT).

Conclusions:

• Hyperglycemia in pregnancy disrupts embryonic lung development by affecting cell apoptosis, proliferation, and differentiation.
• Aberrant Wnt and Fgf signaling activation by hyperglycemia contributes to abnormal lung structure and fibrosis.
• These findings highlight the detrimental effects of maternal diabetes on fetal lung development.