Structural and functional changes in the kidney caused by adverse fetal and neonatal environments

Area of Science:

• Developmental Biology
• Nephrology
• Epigenetics

Background:

• Early developmental environment significantly influences adult health and disease risk.
• Kidney structure and function are particularly susceptible to adverse pre- and perinatal events.
• Low birth weight and preterm birth are associated with reduced nephron number, a known risk factor for kidney disease.

Purpose of the Study:

• To investigate the mechanisms underlying reduced nephron number in intrauterine growth restriction (IUGR) models.
• To explore other structural and functional kidney alterations caused by adverse fetal and neonatal environments.
• To elucidate the role of epigenetic modifications in these changes.

Main Methods:

• Utilized animal models of intrauterine growth restriction (IUGR).
• Investigated ureteric branching, global DNA methylation, and caspase-3 activity.
• Examined structural changes like capillary rarefaction and podocyte endowment.
• Assessed functional changes including nitrosative stress and its impact on kidney injury.

Main Results:

• Adverse developmental environments, including IUGR, lead to reduced nephron number.
• Mechanisms contributing to low nephron number include suppressed ureteric branching, altered DNA methylation, and caspase-3 activity.
• Other structural changes include capillary rarefaction and low podocyte endowment, leading to glomerulosclerosis and fibrosis.
• Functional impairments involve the renin-angiotensin system, sympathetic nervous system, and oxidative stress, potentially linked to epigenetic changes.

Conclusions:

• Adverse early development profoundly impacts kidney development, leading to structural and functional deficits.
• Reduced nephron number, alongside other alterations, predisposes individuals to kidney disease later in life.
• Epigenetic modifications are likely key mechanisms driving these developmental and functional kidney changes.