Murine trophoblast failure and spontaneous abortion.
OBJECTIVE
Infection has been proposed to initiate abortion, and the role of viruses in spontaneous resorption in mice has not been tested.


METHODS
The anti-viral drug ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) was fed to CBA/J and C3H/HeJ female mice beginning on the morning after mating with DBA/2J males.


RESULTS
Ribavirin treatment increased the rate of abortion (resorption) on day 13.5, and this was associated with retardation of the rate of embryo development and hypoplasia of the trophoblast. There was a reduction in trophoblast-dependent decidua-associated soluble suppressor activity, but there was no maternal mononuclear cell infiltrate of the type reported in association with resorption of semiallogeneic and xenogeneic mouse embryos. This may be due to an immunosuppressive effect of ribavirin. Ribavirin was able to potently suppress proliferation of mouse trophoblast and mastocytoma cell lines in vitro.


CONCLUSIONS
There are several drug-induced murine abortion models that provide useful insights into potential mechanisms underlying spontaneous pregnancy failure, but in the ribavirin mode, a direct impairment of trophoblast development appears to be responsible.
Molecular Virology-Immunology Program, McMaster University, Hamilton, Ontario, Canada.
D A
DA
Clark
D
D
Banwatt
B A
BA
Croy
D000022:Abortion, Spontaneous / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005327:Fetal Resorption / Q000209:etiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D011247:Pregnancy; D012254:Ribavirin / Q000633:toxicity; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D014327:Trophoblasts / Q000187:drug effects / Q000276:immunology / Q000473:pathology*
D012254:Ribavirin