Prenatal Effects of Different Intra-Uterine Milieus on Fetal Glucose Sensing Mechanisms during Gestation in Rats

Abstract

The intra-uterine milieu programs the health of an individual throughout life. This effect has been called fetal origin of adult disease. The altered maternal metabolism is associated with a diabetogenic effect in the adult offspring. The pancreatic glucose-stimulated insulin secretion (GSIS) and peripheral response to insulin are central in glucose homeostasis in fetal circulation and the modulation of these processes during the fetal development may have a serious complications long-lasting. This study was aimed to delineate the prenatal (at gestational day 17) effects of different maternal health challenges on the fetal glucose sensing mechanisms including GLUT2, glucokinase, mitochondrial transcription factor A (mTFA), uncoupling protein 2 (UCP2), phospho-insulin receptor (Phosho-IR) and glucose transporter 4 (GLUT4). We used hyperglycemic, obese and malnourished beside normal female rats to establish pregnancy that was terminated at GD 17. The fetal pancreas, liver, muscle and adipose tissues were obtained for determination of the studied parameters. The results indicated up-regulation of GLUT2, glucokinase, mtTFA and UCP2 expression in fetal pancreas and liver of hyperglycemic mothers fetuses while maternal obesity mildly up-regulate expression of GLUT2, glucokinase and UCP2 in fetal pancreas, liver and adipose tissues, while malnutrition causes down-regulation of UCP2 in pancreas, it up-regulates GLUT2 and glucokinase in liver. In muscle and adipose tissues the level of phosho-IR was increased under maternal hyperglycemia and malnutrition while GLUT4 level increased under maternal diabetes only.We can conclude that the fetal adverse environments can prenatally affect the expression of genes that linked to the development of type 2 diabetes including genes controlling glucose sensing and metabolism.

The pre-conception maternal exposure to Sofosbuvir affects the mitochondrial biogenesis in prenatal fetal tissues: Experimental study on rats

“…During pregnancy, the in-utero environment is the vital element that programs to a large extent the health of an individual throughout life because the mammalian fetus is completely dependent on the nutrients supplied by its mother, and any change in this supply or shift in maternal metabolic status can alter fetal development structurally and functionally. This effect has been described as the “fetal origin of adult disease” (Kamel 2012 ). So, we designed this study to examine the possible effects of the pre-conception exposure of young female rats to Sofosbuvir on the pregnancy outcome and the mitochondrial biogenesis and function in different fetal tissues and placental tissue prenatally.…”

Effect of Maternal Diabetes on Pre- and Post-Natal Redox Status of F1 Rat Offspring

“…There are accumulating of evidences that the insulin secretion and action and glucose metabolism regulation are sensitive targets of oxidative stress programming pre and post-natal. Previously we documented impaired glucose sensing and mitochondrial biogenesis and altered expression of uncoupling protein 2 (UCP2) and mitochondrial transcription factor A (mTFA) in the fetal tissues of diabetic gestation at GD 17 these impairments may related to the oxidative stress and shifted redox status [40].…”

The Pre-Conception Maternal Exposure To Sofosbuvir Impacts The Mitochondrial Biogenesis In Prenatal Fetal Tissues: Experimental Study On Rats

“…During pregnancy, the in-utero environment is the vital element that programs to a large extent the health of an individual throughout life because the mammalian fetus is completely dependent on the nutrients supplied by its mother, and any change in this supply or shift in maternal metabolic status can alter fetal development structurally and functionally. This effect has been described as "fetal origin of adult disease" [9] . So, we designed this study to examine the possible effects of the pre-conception exposure of young female rats to Sofosbuvir on the pregnancy outcome and the mitochondrial biogenesis and function in different fetal tissues and placental tissue prenatally.…”