The effect of 6-mercaptopurine on early human placental explants

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 bir...

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Bibliographic Details
Published in:Human reproduction (Oxford) 2005-05, Vol.20 (5), p.1390-1397
Main Authors: Tartakover Matalon, S., Ornoy, A., Fishman, A., Drucker, L., Lishner, M.
Format: Article
Language:English
Subjects:
6-mercaptopurine
Antimetabolites, Antineoplastic - pharmacology
Apoptosis - drug effects
Biological and medical sciences
Cell Movement - drug effects
Cell Proliferation - drug effects
Collagen
Drug Combinations
Female
Gynecology. Andrology. Obstetrics
Hormones - metabolism
Humans
Immunosuppressive Agents - pharmacology
Laminin
Medical sciences
Mercaptopurine - pharmacology
migration
Organ Culture Techniques
placenta
Placenta - cytology
Placenta - drug effects
Placenta - physiology
Pregnancy
Pregnancy Trimester, First
proliferation
Proteoglycans
Trophoblasts - drug effects
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Summary: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.
ISSN:0268-1161
1460-2350
DOI:10.1093/humrep/deh721