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Hum. Reprod. Advance Access originally published online on June 15, 2005
Human Reproduction 2005 20(10):2866-2872; doi:10.1093/humrep/dei120
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© The Author 2005. 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@oupjournals.org

Early Pregnancy

Simvastatin has deleterious effects on human first trimester placental explants

I. Kenis1, S. Tartakover-Matalon1,5, N. Cherepnin2, L. Drucker1, A. Fishman3, M. Pomeranz3 and M. Lishner1,4

1 Oncogenetic Laboratory, Department of Internal Medicine ‘A’, 2 Department of Internal Medicine ‘F’ and 3 Department of Obstetrics & Gynecology, Sapir Medical Center, Kfar-Saba and 4 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

5 To whom correspondence should be addressed at: Oncogenetic Laboratory, Sapir Medical Center, 45 Tshernehovski Str., Kfar-Saba 44281, Israel. E-mail: matalon.shelly{at}clalit.org.il

BACKGROUND: Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMG-CoA reductase), the rate-limiting enzyme of the mevalonate pathway, and have been used successfully in the treatment of hypercholesterolaemia. Animal models have provided evidence for the teratogenic effects of statins on pregnancy outcome. Thus statins are contraindicated during pregnancy. However, conflicting data are available from inadvertent use of statins in human pregnancy. Therefore we decided to explore the effects of simvastatin on the placenta in an in vitro human placental model. METHODS: Human first trimester placental explants that were grown on matrigel were exposed to medium supplemented with simvastatin. Migration of extravillous trophoblast cells was assessed by visual observation. Proliferative and apoptotic events of the trophoblast cells were assesed by immunohistochemical examination using anti-Ki67 and anti-activated caspase-3 antibodies respectively. Hormone levels were measured. RESULTS: Simvastatin sharply inhibited migration of extravillous trophoblast cells from the villi to the matrigel (P < 0.05). Moreover, simvastatin inhibited half of the proliferative events in the villi (P < 0.05) and increased apoptosis of cytotrophoblast cells compared to control. Moreover, simvastatin significantly decreased secretion of progesterone from the placental explants (P < 0.01). CONCLUSION: Simvastatin adversely affects human first trimester trophoblast.

Key words: migration/pregnancy/proliferation/simvastatin/trophoblast


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