Expression of apoptosis-associated molecules in the fetoplacental unit of cyclophosphamide-treated mice.
The mechanisms underlying the teratogen-induced apoptotic process leading to anomaly formation are not as yet understood. Therefore, we tried to evaluate possible changes in the expression of molecules regulating the apoptotic process induced in the embryo and placenta by exposure to cyclophosphamide (CP). Exposure to CP resulted in clear growth retardation that was accompanied by a time-dependent increase in cellular damage and an appearance of apoptotic cells in the embryonic brain and limbs as well as a decrease in cell proliferation. Western blot analysis demonstrated an increase in the level of Bax and a decrease in the expression of the p65 subunit of NF-kappaB and IkappaB alpha in the embryo and placenta. Immunohistochemical analysis localized cells expressing those molecules to the areas that exhibited CP-induced cellular damage, while in the placenta they were revealed mainly in the luminal and glandular epithelium. Our results suggest a possible involvement of Bax, p65 and IkappaB alpha in the response of the embryo and the placenta to teratogenic insults.
Mammon
Keren
K
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel.
Savion
Shoshana
S
Keshet
Rotem
R
Aroch
Ilan
I
Orenstein
Hasida
H
Fein
Amos
A
Torchinsky
Arkady
A
Toder
Vladimir
V
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D016193:G1 Phase / Q000187:drug effects; D005865:Gestational Age; D020672:I-kappa B Proteins / Q000378:metabolism; D007120:Immunochemistry; D020287:In Situ Nick-End Labeling / Q000379:methods; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D050863:Synaptotagmin I / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C494827:Bax protein, mouse; D020672:I-kappa B Proteins; D009153:Mutagens; D050863:Synaptotagmin I; D051028:bcl-2-Associated X Protein; D003520:Cyclophosphamide