Maternal antioxidant treatments prevent diabetes-induced alterations of mitochondrial morphology in rat embryos.
Previous studies have suggested that production of reactive oxygen species by embryonic mitochondria may have a role in the induction of both high-amplitude mitochondrial swelling and embryonic dysmorphogenesis in diabetic pregnancy. The present study analyzed the relationships between a putative metabolite-induced production of free oxygen radicals, mitochondrial lipid peroxidation, and high-amplitude mitochondrial swelling in embryos during organogenesis. For studies in vitro, day 9 embryos of normal rats were cultured for 48 h with a high concentration of glucose in the absence or presence of alpha-cyano-4-hydroxycinnamic acid (CHC), a mitochondrial pyruvate transport inhibitor. The morphology of mitochondria in the neuroepithelium of the embryos was studied with the aid of transmission electron microscopy. For studies in vivo, normal and diabetic pregnant rats were fed a diet supplemented with the antioxidants alpha-tocopherol (vitamin E) or 2,6-di-tert-butyl-4-methylphenol (BHT), and the ultrastructure of mitochondria in the embryonic neuroepithelium and in the visceral yolk sac was investigated on gestational day 11. Exposure to a high concentration of glucose in vitro or to maternal diabetes in vivo induced high-amplitude swelling of mitochondria in the neuroepithelium of the embryos. The swelling of mitochondria was prevented by addition of CHC to the culture media or by maternal ingestion of antioxidant-supplemented food. In diabetic pregnancy, embryonic mitochondria during organogenesis produce free oxygen radicals that cause mitochondrial lipid peroxidation and swelling and furthermore embryonic dysmorphogenesis. Dietary supplementation with antioxidants to the mother may prevent embryonic malformations in diabetic pregnancy by inhibition of mitochondrial dysfunction.
Yang
X
X
Department of Medical Cell Biology, University of Uppsala, Sweden.
Borg
L A
LA
Simán
C M
CM
Eriksson
U J
UJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000196:embryology* / Q000648:ultrastructure; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D003373:Coumaric Acids / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology*; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005609:Free Radicals; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D008933:Mitochondrial Swelling; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D003373:Coumaric Acids; D005609:Free Radicals; D013481:Superoxides; D014810:Vitamin E; D002084:Butylated Hydroxytoluene; C007175:alpha-cyano-4-hydroxycinnamate