Insulin-like growth factor-II and heparin are anti-apoptotic survival factors in human villous cytotrophoblast
Article
Hills, F., Mehmet, H. and Sullivan, M. 2012. Insulin-like growth factor-II and heparin are anti-apoptotic survival factors in human villous cytotrophoblast. European Journal of Obstetrics, Gynecology, and Reproductive Biology. 163 (1), pp. 11-16. https://doi.org/10.1016/j.ejogrb.2012.03.013
Type | Article |
---|---|
Title | Insulin-like growth factor-II and heparin are anti-apoptotic survival factors in human villous cytotrophoblast |
Authors | Hills, F., Mehmet, H. and Sullivan, M. |
Abstract | OBJECTIVE: This study aimed to determine the effects of insulin-like growth factors (IGF-I and IGF-II), heparin, aspirin and vitamin C on the proliferation and apoptosis of human villous cytotrophoblast from first trimester and term placentae. STUDY DESIGN: Villous cytotrophoblast cells were isolated from uncomplicated first trimester (n=12) and term placental tissues (n=12) using negative immunoselection with an antibody to HLA class I antigens. Cells were incubated with IGF-I, IGF-II, heparin, aspirin and vitamin C either alone, or in combination with either TNF-α/IFN-γ or staurosporine. Proliferation was determined by measurement of Ki67 expression using immunocytochemistry. Trophoblast apoptosis was determined by TUNEL staining. Finally RT-PCR was carried out to identify IGF-binding insulin receptor isoforms. Data were expressed as means±SEM. One way analysis of variance (ANOVA) with Bonferroni correction was used to determine if differences between groups were statistically significant. RESULTS: Following negative immunoselection >98% of cells were positively stained for cytokeratin 7, a marker for cytotrophoblasts, and <1% were vimentin positive. First trimester and term trophoblasts underwent spontaneous apoptosis which was inhibited by approximately 50% in the presence of IGF-II or heparin. Apoptosis was significantly increased following incubation with a combination of TNF-α and IFN-γ or staurosporine. Apoptosis was decreased to basal levels following coincubation with IGF-II or heparin. Incubation with IGFs or heparin resulted in a small, but significant increase in Ki67 expression. Insulin receptor isoform A, which binds IGF-II with high affinity, was present in all trophoblast samples tested. CONCLUSION: These results suggest that heparin and IGF-II, but not IGF-I are important regulators of villous cytotrophoblast survival in early and late pregnancy. |
Research Group | Biomarkers for Cancer group |
Reproductive Biology group | |
Centre for Investigative and Diagnostic Oncology | |
Publisher | Elsevier |
Journal | European Journal of Obstetrics, Gynecology, and Reproductive Biology |
ISSN | 1872-7654 |
Publication dates | |
08 Apr 2012 | |
Publication process dates | |
Deposited | 25 May 2012 |
Output status | Published |
Digital Object Identifier (DOI) | https://doi.org/10.1016/j.ejogrb.2012.03.013 |
Language | English |
https://repository.mdx.ac.uk/item/83q35
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