Mild gestational hyperglycemia in rat induces fetal overgrowth and modulates placental growth factors and nutrient transporters expression

• Published in: PloS one Vol. 8; no. 5; p. e64251
• Main Authors: Cisse, Ouma, Fajardy, Isabelle, Dickes-Coopman, Anne, Moitrot, Emmanuelle, Montel, Valérie, Deloof, Sylvie, Rousseaux, Jean, Vieau, Didier, Laborie, Christine
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.05.2013; Public Library of Science (PLoS)
• Subjects: Animals; Biology; Birth Weight; Diabetes; Female; Females; Fetal Development; Fetal Viability; Fetuses; Gene expression; Gene Expression Regulation, Developmental; Genes; Glucose; Glucose tolerance; Glucose Transport Proteins, Facilitative - genetics; Glucose Transport Proteins, Facilitative - metabolism; Glucose transporter; Growth factors; Hyperglycemia; Hypotheses; Insulin; Insulin secretion; Intolerance; Intrauterine exposure; Lipase; Lipids; Lipoprotein lipase; Lipoprotein Lipase - metabolism; Litter Size; Mating; Medicine; Metabolic disorders; Metabolism; Morphology; Neonates; Newborn babies; Niacinamide; Nicotinamide; Nutrients; Offspring; Overexpression; Placenta; Placenta - metabolism; Placenta Growth Factor; Pregnancy; Pregnancy Complications; Pregnancy Proteins - genetics; Pregnancy Proteins - metabolism; Rats; Rats, Wistar; Rodents; Secretion; Streptozocin; Transporter; France
• DOI: 10.1371/journal.pone.0064251
• ISSN: 1932-6203

Mild gestational hyperglycemia is often associated with fetal overgrowth that can predispose the offspring to metabolic diseases later in life. We hypothesized that unfavorable intrauterine environment may compromise the development of placenta and contribute to fetal overgrowth. Therefore, we developed a rat model and investigated the effects of maternal dysglycemia on fetal growth and placental gene expression. Female rats were treated with single injection of nicotinamide plus streptozotocin (N-STZ) 1-week before mating and were studied at gestational day 21. N-STZ pregnant females displayed impaired glucose tolerance that is associated with a lower insulin secretion. Moderate hyperglycemia induced fetal overgrowth in 40% of newborns, from pregnancies with 10 to 14 pups. The incidence of macrosomia was less than 5% in the N-STZ pregnancies when the litter size exceeds 15 newborns. We found that placental mass and the labyrinthine layer were increased in macrosomic placentas. The expression of genes involved in placental development and nutrient transfer was down regulated in the N-STZ placentas of macrosomic and normosomic pups from pregnancies with 10 to 14 ones. However, we observed that lipoprotein lipase 1 (LPL1) gene expression was significantly increased in the N-STZ placentas of macrosomic pups. In pregnancies with 15 pups or more, the expression of IGFs and glucose transporter genes was also modulated in the control placentas with no additional effect in the N-STZ ones. These data suggest that placental gene expression is modulated by gestational conditions that might disrupt the fetal growth. We described here a new model of maternal glucose intolerance that results in fetal overgrowth. We proposed that over-expression of LPL1 in the placenta may contribute to the increased fetal growth in the N-STZ pregnancies. N-STZ model offers the opportunity to determinate whether these neonatal outcomes may contribute to developmental programming of metabolic diseases in adulthood.