Lipoteichoic acid induces preterm delivery in mice.
The purpose of this study was to determine whether or not lipoteichoic acid (LTA) could induce preterm delivery in mice. On days 15 and 17 of pregnancy, female C3H/HeN mice impregnated by male B6D2F1 mice were given intraperitoneal injections of LTA (12.5-75 mg/kg, single dose or repeated doses at a 3-h interval). We examined the changes in cervix, placental trophoblasts, and plasma and amniotic fluid concentrations of interleukin-1alpha (IL-1alpha), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) after dosing with LTA. In addition, the effect of LTA on the contraction of isolated uterine muscle from pregnant mice was also measured. The incidence of preterm delivery was highest (100%), when the pregnant animals were treated with 75 mg/kg LTA twice on day 15 of pregnancy or with 25 mg/kg LTA twice on day 17 of pregnancy. LTA-accelerated cervical ripening and placental abruption preceding the onset of preterm delivery, as well as increased plasma and amniotic fluid concentrations of IL-1alpha, IL-6, and TNF-alpha. Also, LTA increased contraction of uterine muscle strips. In conclusion, LTA induced preterm delivery in mice in the same manner as lipopolysaccharide (LPS), but the effective dose of LTA was larger than that of LPS.
Kajikawa
S
S
Toxicology Laboratory, Mochida Pharmaceutical Co., Ltd., Fujieda, Shizuoka, Japan.
Kaga
N
N
Futamura
Y
Y
Kakinuma
C
C
Shibutani
Y
Y
D000653:Amniotic Fluid / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D020070:Cervical Ripening / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D007752:Obstetric Labor, Premature / Q000139:chemically induced*; D010920:Placenta / Q000187:drug effects; D011247:Pregnancy; D013682:Teichoic Acids / Q000633:toxicity*; D014590:Uterine Contraction / Q000187:drug effects
D016207:Cytokines; D008070:Lipopolysaccharides; D013682:Teichoic Acids; C009900:lipoteichoic acid