title: Diabetes-induced perturbations are subject to intergenerational transmission through maternal line.
abstract: The hypothesis of fetal origins of adult disease states that early life events program the occurrence of significant adult diseases, including diabetes and obesity. Maternal diabetes is associated with general stress environment for developing fetus, and gestational diabetes is an independent risk factor for type 2 diabetes and metabolic syndrome in offspring. Intra-uterine fetal programming of fetal tissues exposes the offspring to increased risk of impaired glucose tolerance, type 2 diabetes, and cardiovascular disease. Here, we examined the transmission of maternal diabetes-induced fetal programming in second generation and compared maternal and paternal routes of intergenerational effects. We organized 40 Wistar rats into three groups, male offspring of diabetic mothers, female offspring of diabetic mothers, and offspring of control mothers. These groups were mated with normal healthy rats to assess the effect of grand-maternal diabetes on pregnancy outcome in F2 rats, as well as glucose-sensing parameters, insulin resistance, and glucose tolerance prenatally and postnatally. We found that F2 offspring of diabetic mothers had impaired glucose sensing, increased oxidative stress, insulin resistance, and impaired glucose tolerance, and these effects were more prominent in the F2 offspring of F1 female rats (F2-DF1F). We deduce that fetal programming of maternal diabetes is mostly transmitted through maternal line across two generations.
authors.affiliation: Department of Biochemistry, Medical Research Institute, Alexandria University, 165 Elhorreya, Avenue, P.O. Box 21561, Alexandria, Egypt.
authors.forename: Mervat Y
authors.initials: MY
authors.lastname: Hanafi
authors.affiliation: Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt.
authors.forename: Taha M
authors.initials: TM
authors.lastname: Abdelkhalek
authors.affiliation: Department of Biochemistry, Medical Research Institute, Alexandria University, 165 Elhorreya, Avenue, P.O. Box 21561, Alexandria, Egypt. m.ibrahim1988@hotmail.com.|The Ritchie Centre, Hudson Institute of Medical Research, Monash University, Melbourne, Victoria, Australia. m.ibrahim1988@hotmail.com.
authors.forename: Mohamed I
authors.initials: MI
authors.lastname: Saad
authors.affiliation: Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt.
authors.forename: Moustafa M
authors.initials: MM
authors.lastname: Saleh
authors.affiliation: Department of Biochemistry, Medical Research Institute, Alexandria University, 165 Elhorreya, Avenue, P.O. Box 21561, Alexandria, Egypt.
authors.forename: Maha M
authors.initials: MM
authors.lastname: Haiba
authors.affiliation: Department of Biochemistry, Medical Research Institute, Alexandria University, 165 Elhorreya, Avenue, P.O. Box 21561, Alexandria, Egypt.
authors.forename: Maher A
authors.initials: MA
authors.lastname: Kamel
mesh_terms: D000273:Adipose Tissue / Q000196:embryology / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D047109:Fetal Development; D018507:Gene Expression Regulation, Developmental; D018149:Glucose Intolerance / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008297:Male; D000072741:Maternal Inheritance; D063154:Mitochondrial Dynamics; D018482:Muscle, Skeletal / Q000196:embryology / Q000378:metabolism; D001678:Organelle Biogenesis; D018384:Oxidative Stress; D010179:Pancreas / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: D013311:Streptozocin
keywords: Diabetes; Fetal origin of disease; Fetal programming; Glucose sensing; Oxidative stress