Back to Search
Start Over
IFN- -mediated extravillous trophoblast outgrowth inhibition in first trimester explant culture: a role for insulin-like growth factors
- Source :
- Molecular Human Reproduction. 14:281-289
- Publication Year :
- 2008
- Publisher :
- Oxford University Press (OUP), 2008.
-
Abstract
- Pre-eclampsia is often associated with inadequate cytotrophoblast invasion and remodelling of the uterine spiral arteries. Examining a first trimester, 2D in vitro explant culture model which mimics in vivo placentation, including trophoblast column formation and extravillous cytotrophoblast (EVT) migration, we previously suggested that excessive maternal decidual natural killer cell interferon (IFN-gamma) limits EVT migration. Types-1 and -2 insulin-like growth factor (IGF-1, IGF-2) are trophic for EVT, act through their surface receptors, IGFR-1 and IGFR-2, and are regulated by the IGF-binding proteins (IGFBPs). Could the observed IFN-gamma-mediated inhibition of EVT outgrowth and migration be related to either expression changes of IGF-1 or IGF-2, their receptors, their binding proteins, or apoptosis? Using the 2D explant culture model, we examined the effect of IFN-gamma exposure on IGF-1 and -2, IGFR-1 and -2, IGFBPs and apoptosis. IFN-gamma relatively increased IGF-1 and -2 secretion. In EVT, IFN-gamma decreased IGFR-2, but not IGFR-1 expression. IGBP-2, -3 and -4 production were not influenced by IFN-gamma. IFN-gamma induced trophoblast apoptosis measured by the highly sensitive M30 neo-epitope, but not caspase 3 activity, in conditioned medium and EVT cell lysates. The observed IFN-gamma-mediated EVT migration inhibition may occur through the down-regulation of IGFR-2 and subtle induction of EVT apoptosis.
- Subjects :
- Integrins
Embryology
medicine.medical_specialty
medicine.medical_treatment
Down-Regulation
Apoptosis
Biology
Receptor, IGF Type 2
Receptor, IGF Type 1
Natural killer cell
Interferon-gamma
Insulin-like growth factor
Organ Culture Techniques
Cell Movement
Insulin-Like Growth Factor II
Pregnancy
Somatomedins
Internal medicine
Genetics
medicine
Humans
Insulin-Like Growth Factor I
Receptor
Molecular Biology
Cells, Cultured
Cytotrophoblast
Growth factor
Obstetrics and Gynecology
Trophoblast
Placentation
Cell Biology
Trophoblasts
Cell biology
Insulin-Like Growth Factor Binding Proteins
Pregnancy Trimester, First
medicine.anatomical_structure
Endocrinology
Reproductive Medicine
Female
Cell Surface Extensions
Chorionic Villi
Developmental Biology
Explant culture
Subjects
Details
- ISSN :
- 14602407 and 13609947
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Molecular Human Reproduction
- Accession number :
- edsair.doi.dedup.....1973227474a92aad73131e9519b8a1a6