Insulin-like growth factor-II and heparin are anti-apoptotic survival factors in human villous cytotrophoblast

Hills, Frank and Mehmet, Huseyin and Sullivan, Mark H (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. ISSN 1872-7654

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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.

Item Type:Article
Research Areas:A. > School of Science and Technology > Natural Sciences > Biomarkers for Cancer group
A. > School of Science and Technology > Natural Sciences > Reproductive Biology group
A. > School of Health and Education > Centre for Investigative and Diagnostic Oncology
A. > School of Science and Technology > Natural Sciences
Citations on ISI Web of Science:0
ID Code:9074
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Deposited On:25 May 2012 09:18
Last Modified:16 Mar 2015 16:12

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