Effect of maternal diabetes and hypercholesterolemia on fetal liver of albino Wistar rats.
OBJECTIVE
The aim of this study was to predict the development of hepatic lesions and impairment of function during the development of fetuses (13-, 15-, 17-, and 19-d-old embryos) of diabetic and hypercholesterolemic mothers.


METHODS
Eighty virgin and fertile male rats (one male/three females) of Wistar strain with an average body weight of 150 to 180 g were used. Mating was carried out, and pregnancy was determined by examining sperm in vaginal smears. Pregnant rats were arranged into three groups; control, diabetic (single intraperitoneal injection [i.p.] of 60 mg streptozotocin/kg) and hypercholesterolemic groups (fed on a diet containing 3% cholesterol for 6 wk before conception and throughout gestation) (n = 20). Pregnant rats were sacrificed and 13-, 15-, 17-, and 19-d-old embryos and livers were incised and subjected to histological and transmission electronic microscopical (TEM) investigations, assessments of alkaline phosphatase (Al-Pase) isoenzymes electrophoresis, DNA fragmentation, and comet assay. Flow cytometric analysis of apoptosis and caspases 3 and 9 in the livers of mother rats and their 19-d-old fetuses was determined.


RESULTS
Histologic findings of diabetic and hypercholesterolemic mothers revealed apparent damage of hepatocytes, accumulation of lipid-laden cells, and vascular steatosis, while the 13-, 15-, 17- or 19-d-old fetuses of either diabetic or hypercholesterolemic mothers revealed disorganized hepatic architecture and massive cell damage. TEM of diseased mothers and their fetuses possessed increased incidence of pyknotic hepatocytes with massive vesicuolation of rough endoplasmic reticulum and degeneration of mitochondria. Al-Pase isoenzymes were altered and genomic DNA of both double and single helical structures were markedly damaged, especially in fetuses of maternally diabetic and hypercholesterolemic mothers. Flow cytometry revealed an increase in apoptosis and caspases 3 and 9 in diabetic and hypercholesterolemic mothers and their 19-d-old fetuses.


CONCLUSIONS
These results suggested that maternal diabetes and hypercholesterolemia predicted early hepatitis and increased apoptosis in mothers and their fetuses as a result of oxidative stress and elevated apoptic markers caspases 3 and 9.
Department of Zoology, Department of Zoology, Faculty of Science, Mansoura University, Dakahlea, Egypt. Electronic address: elsayyad@mans.edu.eg.
Hassan I H
HI
El-Sayyad
Pediatric and Genetic Department, Faculty of Medicine, Mansoura University, Dakahlea, Egypt.
Mohamed M S
MM
Al-Haggar
Department of Zoology, Department of Zoology, Faculty of Science, Mansoura University, Dakahlea, Egypt.
Heba A
HA
El-Ghawet
Department of Zoology, Department of Zoology, Faculty of Science, Mansoura University, Dakahlea, Egypt.
Iman H M
IH
Bakr
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D020552:Comet Assay; D053938:DNA Fragmentation; D003921:Diabetes Mellitus, Experimental / Q000473:pathology; D016640:Diabetes, Gestational / Q000473:pathology*; D004721:Endoplasmic Reticulum / Q000473:pathology; D005260:Female; D005333:Fetus; D022781:Hepatocytes / Q000473:pathology; D006937:Hypercholesterolemia / Q000473:pathology*; D008099:Liver / Q000473:pathology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria; D018384:Oxidative Stress / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
D001786:Blood Glucose; D013311:Streptozocin; D000469:Alkaline Phosphatase; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9
Alkaline phosphatase electrophopresis; Apoptosis; Caspases 3 and 9; DNA damage; Diabetes; Fetus; Flow cytometry; Hypercholesterolemia; Light and ultrastructure; Liver