Repeated administration of low-dose lipopolysaccharide induces preterm delivery in mice: a model for human preterm parturition and for assessment of the therapeutic ability of drugs against preterm delivery.
OBJECTIVE
Our purpose was to establish a new animal model for human preterm delivery for assessment of the protective effect of drugs against preterm delivery.


METHODS
C3H/HeN, C3H/HeN, and BALB/c female mice impregnated by C3H/HeN, B6D2F1, and B6D2F1 male mice, respectively, were treated intraperitoneally with Escherichia coli lipopolysaccharide (0 to 100 microgram/kg, single dose or repeated doses at 1- to 6-hour intervals) on days 12 through 17 of pregnancy. On day 15 of pregnancy, the C3H/HeN females that had been impregnated by B6D2F1 males and administered lipopolysaccharide were treated intraperitoneally with indomethacin (1000 microgram/kg), ritodrine hydrochloride (1000 microgram/kg), urinary trypsin inhibitor (25 x 10(4) units/kg), or gabexate mesylate (100 mg/kg); preterm or term delivery was recorded for these mice.


RESULTS
C3H/HeN females impregnated by B6D2F1 males revealed the highest (100%) incidence of preterm delivery when the females were treated with 50 microgram/kg lipopolysaccharide twice at a 3-hour interval on day 15 or 17 of pregnancy. Indomethacin and urinary trypsin inhibitor used separately significantly decreased the incidence of preterm delivery, but only urinary trypsin inhibitor, and not any of the other drugs, significantly increased the incidence of term delivery in the mice.


CONCLUSIONS
A new animal model for investigation of preterm delivery was established, and its usefulness for assessment of the protective effect of drugs against preterm delivery was demonstrated.
Kaga
N
N
Toxicology Laboratory, Mochida Pharmaceutical Co., Ltd., Shizuoka, Japan.
Katsuki
Y
Y
Obata
M
M
Shibutani
Y
Y
D000818:Animals; D004195:Disease Models, Animal; D004926:Escherichia coli; D005260:Female; D016670:Gabexate / Q000627:therapeutic use; D006023:Glycoproteins / Q000627:therapeutic use; D006801:Humans; D007213:Indomethacin / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D051379:Mice; D008809:Mice, Inbred C3H; D007752:Obstetric Labor, Premature / Q000139:chemically induced* / Q000188:drug therapy*; D011247:Pregnancy; D012312:Ritodrine / Q000627:therapeutic use; D015149:Tocolytic Agents / Q000627:therapeutic use; D014361:Trypsin Inhibitors / Q000627:therapeutic use
D006023:Glycoproteins; D008070:Lipopolysaccharides; D015149:Tocolytic Agents; D014361:Trypsin Inhibitors; D016670:Gabexate; D012312:Ritodrine; C028665:urinastatin; D007213:Indomethacin