Busulfan-induced apoptosis in rat placenta.
In order to investigate the effects of busulfan on the placenta, we examined the sequential histopathological changes in the placenta from rats exposed to busulfan during gestation days (Days) 12-14. Busulfan was intraperitoneally administered at 10 mg/kg on Days 12, 13 and 14, and the placentas were sampled on Day 13.5, 14.5, 15, 16 or 21. Macroscopically, small placenta was seen on Day 21 with scattered white spots and white peripheral rim. Histopathologically, in the treated group, there were increased apoptosis and decreased mitotic activities in the trophoblasts of the labyrinth zone on Days 13.5, 14.5, 15 and 16. In the basal zone, slightly increased apoptosis was seen on Day 13.5 and slightly decreased mitotic activity on Day 14.5. On Day 21, the labyrinth zone in the treated group was reduced in diameter. Degeneration and necrosis of trophoblasts, a diminution in thickness of the trophoblastic septa with a deposition of calcium and an irregular dilation of the maternal blood space were scattered in the labyrinth zone, although there were no conspicuous changes in the basal zone. The anti-proliferative effects of busulfan could have inhibited the development of the labyrinth zone, and led to small placentas. The fetotoxicity and teratogenicity of busulfan might be also responsible for these placental changes.
Furukawa
Satoshi
S
Biological Research Laboratories, Nissan Chemical Industries Ltd., 1470 Shiraoka, Minamisaitama Saitama 349-0294, Japan. furukawa@nissanchem.co.jp
Usuda
Koji
K
Abe
Masayoshi
M
Hayashi
Seigo
S
Ogawa
Izumi
I
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002066:Busulfan / Q000633:toxicity*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D020567:Fetal Weight / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008938:Mitosis / Q000187:drug effects; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors; D014327:Trophoblasts / Q000187:drug effects* / Q000473:pathology
D000477:Alkylating Agents; D002066:Busulfan