Maternal clofibrate administration amplifies fetal peroxisomes.
To study the effects of peroxisome proliferators on fetal biogenesis, 400 mg/kg oral clofibrate was administered to pregnant mice beginning at d 6 of gestation. Maternal/fetal tissues from three separate experiments were harvested between gestational d 13 and 19 and maternal/fetal tissues were assayed for peroxisomal matrix, membrane-associated, and integral membrane proteins. By comparison to control pregnancies that received vehicle only, clofibrate produced a 4- to 5-fold increase in the levels of peroxisomal membrane protein 70, a 1.5- to 2-fold increase of dihydroxyacetone phosphate acyltransferase (DHAP-AT) sp act, and a 1.2- to 1.8-fold increase of catalase sp act in fetal liver of 19 d gestation. Fetal liver endoplasmic reticulum and peroxisomes were also amplified as visualized by electron microscopy. Clofibrate exhibited maximal effects on maternal tissues by 6 d of oral treatment with increases in peroxisomal membrane protein 70 occurring most clearly in maternal liver; DHAP-AT activity was increased in maternal liver, kidney, and brain but not in lung. Slight increases in DHAP-AT activities were evident in fetal brain, lung, and placenta as compared with the greater increases in liver and kidney. There was a general increase in peroxisomal proteins between 13 and 19 gestational d in all fetal tissues except placenta, and the effect of clofibrate was evident by gestational d 13 in lung and placenta. Minimal changes in the activities of acid phosphatase (lysosomal enzyme) or glycerol-3-phosphate acyltransferase (microsomal enzyme) were observed in maternal or fetal tissues although the latter enzyme was increased 10-30% by clofibrate in maternal brain, fetal lung, and placenta.(ABSTRACT TRUNCATED AT 250 WORDS)
Wilson
G N
GN
Department of Pediatrics, University of Texas, Southwestern Medical Center, Dallas 75235.
King
T
T
Argyle
J C
JC
Garcia
R F
RF
D018528:ATP-Binding Cassette Transporters; D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D002994:Clofibrate / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008431:Maternal-Fetal Exchange; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008830:Microbodies / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D011247:Pregnancy
D018528:ATP-Binding Cassette Transporters; C489271:Abcd3 protein, mouse; D008565:Membrane Proteins; D000217:Acyltransferases; C020051:glycerone-phosphate O-acyltransferase; D002994:Clofibrate