A Potential Role for GSK3βin Glucose-Driven Intrauterine Catch-Up Growth in Maternal Obesity
| Autor: | Alexandra Gellhaus, Sarah Storck, Jörg Dötsch, Eva Hucklenbruch-Rother, Jon Grothe, Maria Wohlfarth, Marion Handwerk, Inga Bae-Gartz, Sarah Appel, Ruth Janoschek |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Offspring Placenta Placental Finding Medizin Intrauterine growth restriction 030209 endocrinology & metabolism Biology Fetal Development Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Pregnancy Internal medicine medicine Animals Obesity reproductive and urinary physiology Fetus Fetal Growth Retardation Glycogen Synthase Kinase 3 beta Glycogen medicine.disease 030104 developmental biology medicine.anatomical_structure chemistry Gestation Female |
| Zdroj: | Endocrinology. 160:377-386 |
| ISSN: | 1945-7170 |
| DOI: | 10.1210/en.2018-00899 |
| Popis: | Obesity and unhealthy nutrition are increasing and affect women of childbearing age and hence during pregnancy. Despite normal or even high birth weight, the offspring suffers from long-term metabolic risks. We hypothesized that fetal growth is disturbed during different intrauterine phases. Underlying molecular events remain elusive. Female mice were fed either a standard diet (SD) or a high-fat diet (HFD) after weaning until mating and during pregnancy. Pregnant mice were euthanized at gestational day (G)15.5 and G18.5, and fetuses and placentas were removed for analysis. HFD fetuses displayed intrauterine growth restriction (IUGR) at G15.5, which disappeared until G18.5, indicating intrauterine catch-up growth during that time period. Main placental findings indicate decreased canonical Wnt-GSK3β signaling and lower proliferation rates at G18.5, which goes along with a smaller placental transfer zone. On the other hand, glucose depots (glycogen cluster) in HFD placentas decreased more strongly between G15.5 and G18.5 compared with placentas from SD mothers, and the glucose transporter protein GLUT-1 was increased at G18.5 in the HFD group. Maternal diet-induced obesity causes an IUGR phenotype at the beginning of the third week (G15.5) in our mouse model. This phenotype is reversed by the end of the third week (G18.5) despite a smaller placental transfer zone, probably based on GSK3β-mediated increased glucose mobilization in the placenta and hence an increased glucose supply to the fetus. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|