Skip Navigation


Hum. Reprod. Advance Access originally published online on December 11, 2006
Human Reproduction 2007 22(4):1161-1167; doi:10.1093/humrep/del464
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF ) Freely available
Right arrow All Versions of this Article:
22/4/1161    most recent
del464v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (2)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Tartakover-Matalon, S.
Right arrow Articles by Lishner, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tartakover-Matalon, S.
Right arrow Articles by Lishner, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Impaired migration of trophoblast cells caused by simvastatin is associated with decreased membrane IGF-I receptor, MMP2 activity and HSP27 expression

S. Tartakover-Matalon1,5, N. Cherepnin1, M. Kuchuk2, L. Drucker1,4, I. Kenis2, A. Fishman3,4, M. Pomeranz3 and M. Lishner1,2,4

1 Oncogenetic Laboratory 2 Department of Medicine 3 Department of Obstetrics & Gynecology, Meir Medical Centre, Kfar-Saba 4 Sackler Faculty of Medicine, Tel–Aviv University, Israel

5 To whom corresponding should be addressed at: Oncogenetic Laboratory, Meir Medical Centre, 45 Tshernehovski ST. Kfar-Saba, 44281, Israel. E-mail: matalon.shelly{at}clalit.org.il

BACKGROUND: Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme-A reductase, the rate-limiting enzyme of the mevalonate pathway, and are used successfully in the treatment of hypercholesterolaemia. Statins are contraindicated during pregnancy. Lately, we have shown that simvastatin has adverse affects on human first trimester placental explants' proliferation and migration. The objective of the present study was to investigate the molecules involved in mediating simvastatin's effect on trophoblast cell migration. We hypothesized that simvastatin attenuates insuline-like growth factor-I (IGF-I) receptor expression (involved in trophoblast motility), matrix metalloproteinase (MMP) activities, and heat shock protein 27 (HSP27) levels (whose mRNA is actively transcribed during trophoblast differentiation) in trophoblast cells thus consequently effecting their migration.

METHODS: Human placental explants were cultured above a matrigel with/without simvastatin (10 µM) for 5 days. In this model, trophoblast migrates from the villi into the matrigel. Western-blot and immunohistochemistry served for analysing HSP27 expression. Immunohistochemistry was used for assessing IGF-I receptor localization. MMPs activity was assayed by gel zymography.

RESULTS: Simvastatin reduced IGF-I receptor membranal expression, MMP2 activity and HSP27 expression in trophoblast cells (P < 0.05).

CONCLUSIONS: The inhibitory effect of simvastatin on trophoblast cell migration is associated with a significant decrease in the tested molecules, which probably contributes to the impaired migration.

Key words: HSP27/IGF-IR/MMP2/simvastatin/trophoblast

Submitted on March 8, 2006; resubmitted on June 12, 2006; resubmitted on October 30, 2006; accepted on November 7, 2006.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.