Intrauterine low-protein diet disturbs metanephric gene expression and induces urinary tract developmental

Minghui Yu1, Lihong Tan1, Jing Chen1

  • 1Department of Nephrology, Children's Hospital of Fudan University, Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.

Insights

Maternal low-protein diet during pregnancy is linked to congenital anomalies of the kidney and urinary tract (CAKUT) in offspring. This diet impacts kidney development, increasing CAKUT incidence, particularly duplicated collecting systems.

Area of Science:

  • Developmental Biology
  • Nephrology
  • Teratology

Background:

  • Intrauterine environment significantly influences fetal development, including kidney formation.
  • Maternal nutrition, specifically protein intake, is a critical factor in organogenesis.
  • Congenital anomalies of the kidney and urinary tract (CAKUT) represent a spectrum of developmental abnormalities with significant clinical impact.

Purpose of the Study:

  • To investigate the impact of an intrauterine low-protein diet on kidney development.
  • To identify specific CAKUT phenotypes associated with intrauterine low-protein diet.
  • To elucidate the molecular mechanisms underlying diet-induced CAKUT.

Main Methods:

  • Animal model of intrauterine low-protein diet exposure.
  • Histological analysis of kidney development and nephron number.
  • Assessment of ureteric bud branching and gene expression.
  • Western blot analysis for protein signaling pathways and apoptosis.

Main Results:

  • Intrauterine low-protein diet induced CAKUT phenotypes, predominantly duplicated collecting systems.
  • Increased ectopic ureteric buds and reduced ureteric bud branching were observed.
  • Downregulation of Slit2/Robo2 and Spry1, alongside increased Ret expression, was noted.
  • Enhanced p-Akt activity and abnormal apoptosis in ureteric bud tissue were detected.

Conclusions:

  • Intrauterine low-protein diet is correlated with an increased incidence of CAKUT in offspring.
  • Altered gene expression and signaling pathways (Slit2/Robo2, Spry1, Ret, Akt) in ureteric buds are implicated mechanisms.
  • This study highlights the critical role of maternal nutrition in preventing congenital kidney anomalies.

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