Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kutasy, B; Friedmacher, F; Duess, JW; Puri, P.
Prenatal administration of retinoic acid increases the trophoblastic insulin-like growth factor 2 protein expression in the nitrofen model of congenital diaphragmatic hernia.
Pediatr Surg Int. 2014; 30(2): 137-142.
Doi: 10.1007/s00383-013-3449-7
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Friedmacher Florian
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- Abstract:
- The high mortality rate in congenital diaphragmatic hernia (CDH) is attributed to pulmonary hypoplasia (PH). Insulin-like growth factor 2 (IGF2) is an important regulator of fetal growth. The highest levels of IGF2 expression are found in the placenta, which are negatively regulated by decidual retinoid acid receptor alpha (RARα). It has been demonstrated that prenatal administration of retinoic acid (RA) suppresses decidual RARα expression. Previous studies have further shown that prenatal administration of RA can reverse PH in nitrofen-induced CDH model. In IGF2 knockout animals, low levels of IGF2 are associated with decreased placental growth and PH. We therefore hypothesized that nitrofen decreases trophoblastic IGF2 expression and prenatal administration of RA increases it through decidual RARα in the nitrofen-induced CDH model. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). RA was given intraperitoneally on D18, D19 and D20. Fetuses were harvested on D21 and divided into three groups: control, CDH and nitrofen+RA. Immunohistochemistry was performed to evaluate decidual RARα and trophoblastic IGF2 expression. Protein levels of IGF2 in serum, intra-amniotic fluid and left lungs were measured by enzyme-linked immunosorbent assay. Significant growth retardation of placenta and left lungs was observed in the CDH group compared to control and nitrofen+RA group. Markedly increased decidual RARα and decreased IGF2 immunoreactivity were found in the CDH group compared to control and nitrofen+RA group. Significantly decreased IGF2 protein levels were detected in serum, intra-amniotic fluid and left lungs in the CDH group compared to control and nitrofen+RA group. Our findings suggest that nitrofen may disturb trophoblastic IGF2 expression through decidual RARα resulting in retarded placental growth and PH in the nitrofen-induced CDH. Prenatal administration of RA may promote lung and placental growth by increasing trophoblastic IGF2 expression.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antineoplastic Agents - pharmacology
- Disease Models, Animal -
- Enzyme-Linked Immunosorbent Assay - methods
- Female -
- Gene Expression Regulation, Developmental - drug effects Gene Expression Regulation, Developmental - genetics
- Hernia, Diaphragmatic - embryology Hernia, Diaphragmatic - genetics Hernia, Diaphragmatic - metabolism
- Hernias, Diaphragmatic, Congenital -
- Insulin-Like Growth Factor II - drug effects Insulin-Like Growth Factor II - genetics Insulin-Like Growth Factor II - metabolism
- Lung - drug effects Lung - embryology Lung - metabolism
- Phenyl Ethers -
- Pregnancy -
- Rats -
- Rats, Sprague-Dawley -
- Reverse Transcriptase Polymerase Chain Reaction - methods
- Tretinoin - pharmacology
- Trophoblasts - drug effects Trophoblasts - metabolism
- Up-Regulation - drug effects Up-Regulation - genetics
- Find related publications in this database (Keywords)
- Trophoblast
- Insulin-like growth factor 2
- Retinoic acid
- Nitrofen
- Congenital diaphragmatic hernia