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Hum. Reprod. Advance Access first published online on March 10, 2005
This version published online on March 24, 2005
Human Reproduction, doi:10.1093/humrep/deh721
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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
Received May 4, 2004
Revised September 8, 2004
Accepted December 7, 2004

Article

The effect of 6-mercaptopurine on early human placental explants

S. Tartakover Matalon 1*, A. Ornoy 2, A. Fishman 3, L. Drucker 1, and M. Lishner 1

1 Oncogenetic laboratory, Department of Medicine ‘A’, Sapir Medical Center, Kfar-Saba 44281, Jerusalem, Israel
2 Laboratory of Teratology, Department of Anatomy and Cell Biology, Hebrew University Hadassah Medical School, Jerusalem, Israel
3 Department of Obstetrics & Gynecology, Sapir Medical Center, Kfar-Saba 44281 Tel-Aviv University, Tel-Aviv, Israel, Jerusalem, Israel

* To whom correspondence should be addressed.
S. Tartakover Matalon, E-mail: matalon.shelly{at}clalit.org.il


  Abstract

BACKGROUND: 6-mercaptopurine (6-MP) is an antineoplastic and immunosuppressive drug. Recently, more women have received this drug during pregnancy. Animal studies have shown that 6-MP has deleterious effects on the fetus, while human data include prematurity, intrauterine growth restriction, low birth weight and malformations that occur especially when the drug is administered in the first trimester of pregnancy. OBJECTIVES: To study the effects of 6-MP on cellular functions of human trophoblast explants. METHODS: Human placental explants (5.5-9 weeks gestational age), that were grown on matrigel, were exposed to medium containing 6-MP for 5 days. Medium alone served as control. Extravillous trophoblast (EVT) cell migration assessment was performed by visual observation. Analysis of proliferating events of the trophoblast cells was asessed by immunohistochemical examination. Apoptosis was analyzed by Tunnel procedure and by anti-caspase 3 staining and hormone level by enzyme-linked immunosorbent assay. RESULTS: 6-MP inhibited migration of EVT cells from the villi to the matrigel with a lower proliferation rate and increased apoptosis of cytotrophoblast cells compared to controls. However, no significant effect of 6-MP on hormone levels was observed. CONCLUSIONS: 6-MP inhibited migration and proliferation of trophoblast cells in first-trimester human placental explant culture.

Keywords: 6-mercaptopurine; migration; placenta; pregnancy; proliferation.
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