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 birth weight and malformations that occur especially when the drug is administered in the first trimester of pregnancy.


OBJECTIVE
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 assessed 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.
Matalon
S Tartakover
ST
Oncogenetic laboratory, Department of Medicine A, Sapir Medical Center, Kfar-Saba 44281 Tel-Aviv University, Israel.
Ornoy
A
A
Fishman
A
A
Drucker
L
L
Lishner
M
M
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen; D004338:Drug Combinations; D005260:Female; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007797:Laminin; D015122:Mercaptopurine / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010920:Placenta / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011509:Proteoglycans; D014327:Trophoblasts / Q000187:drug effects
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D006728:Hormones; D007166:Immunosuppressive Agents; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D015122:Mercaptopurine