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Related Experiment Videos

Maternal clofibrate administration amplifies fetal peroxisomes.

G N Wilson1, T King, J C Argyle

  • 1Department of Pediatrics, University of Texas, Southwestern Medical Center, Dallas 75235.

Pediatric Research
|March 1, 1991
PubMed
Summary

Peroxisome proliferators like clofibrate significantly increase peroxisomal proteins in fetal tissues, impacting biogenesis during gestation. This study reveals clofibrate

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Area of Science:

  • Developmental toxicology
  • Peroxisome biogenesis and function
  • Pharmacology

Background:

  • Peroxisome proliferators are xenobiotics known to induce peroxisome proliferation.
  • Understanding their impact on fetal development is crucial for assessing potential risks.

Purpose of the Study:

  • To investigate the effects of clofibrate, a peroxisome proliferator, on fetal biogenesis.
  • To quantify changes in peroxisomal proteins and enzyme activities in maternal and fetal tissues during gestation.

Main Methods:

  • Pregnant mice were administered oral clofibrate (400 mg/kg) from gestational day 6.
  • Maternal and fetal tissues were harvested between gestational days 13 and 19.
  • Assays were performed for peroxisomal matrix, membrane-associated, and integral membrane proteins, as well as enzyme activities.

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Main Results:

  • Clofibrate significantly increased peroxisomal membrane protein 70 (4-5 fold), dihydroxyacetone phosphate acyltransferase (DHAP-AT) activity (1.5-2 fold), and catalase activity (1.2-1.8 fold) in fetal liver.
  • Electron microscopy confirmed amplification of fetal liver endoplasmic reticulum and peroxisomes.
  • Maternal liver showed the most pronounced increase in peroxisomal membrane protein 70; DHAP-AT activity increased in maternal liver, kidney, and brain, with slight increases in fetal brain, lung, and placenta.

Conclusions:

  • Oral administration of clofibrate during gestation effectively induces peroxisome proliferation in fetal tissues, particularly the liver.
  • The study demonstrates clofibrate's impact on peroxisomal biogenesis and protein levels during critical stages of fetal development.
  • These findings highlight the potential for environmental or pharmaceutical agents to influence fetal organelle development.