Document Detail

Simvastatin has deleterious effects on human first trimester placental explants.
MedLine Citation:
PMID:  15958395     Owner:  NLM     Status:  MEDLINE    
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.
I Kenis; S Tartakover-Matalon; N Cherepnin; L Drucker; A Fishman; M Pomeranz; M Lishner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-06-15
Journal Detail:
Title:  Human reproduction (Oxford, England)     Volume:  20     ISSN:  0268-1161     ISO Abbreviation:  Hum. Reprod.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-09-26     Completed Date:  2006-01-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8701199     Medline TA:  Hum Reprod     Country:  England    
Other Details:
Languages:  eng     Pagination:  2866-72     Citation Subset:  IM    
Oncogenetic Laboratory, Department of Internal Medicine A, Sapir Medical Center, Kfar-Saba, Israel.
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MeSH Terms
Caspase 3
Caspases / immunology,  metabolism
Cell Movement
Cell Proliferation
Collagen / pharmacology
Drug Combinations
Hydroxymethylglutaryl-CoA Reductase Inhibitors / toxicity*
Hypercholesterolemia / drug therapy
Ki-67 Antigen / biosynthesis
Laminin / pharmacology
Placenta / drug effects*,  pathology
Pregnancy Outcome
Pregnancy Trimester, First
Progesterone / metabolism
Proteoglycans / pharmacology
Simvastatin / toxicity*
Time Factors
Trophoblasts / cytology,  metabolism
Reg. No./Substance:
0/Drug Combinations; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Ki-67 Antigen; 0/Laminin; 0/Proteoglycans; 0/Teratogens; 119978-18-6/matrigel; 57-83-0/Progesterone; 79902-63-9/Simvastatin; 9007-34-5/Collagen; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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