Ability of intrauterine bacterial lipopolysaccharide to cause in situ uterine contractions in pregnant rabbits


Toxicology Laboratory Mochida Pharmaceutical Co. Ltd. 342 Gensuke, Fujieda, Shizuoka, 426, Japan


Background. To investigate the ability of bacterial lipopolysaccharide delivered by the intrauterine route to cause uterine contractions in rabbits, and to assess the suppressive effect of urinar trypsin inhibitor on them.

Methods. Both pregnant and non-pregnant rabbits were chronically implanted with a force-transducer to make it possible to record isometric uterine contractions under unanesthetized and unrestrained conditions. Lipopolysaccharide (10 mg/animal) was administered via a catheter to their uteri: and then, after confirmation of lipopolysaccharide-induced uterine contractions. urinary trypsin inhibitor (3.000 or 10.000 units/animal/time) or saline solution was injected through the catheter, 5 times for pregnant animals or 3 times for non-pregnant animals at 1-hour intervals in both cases. Their uterine contractions were continuously recorded for 3 to 5 hours. Effects of lipopolysaccharide (10 ug/ml) and urinary trypsin inhibitor (100 and 1.000 units/ml) on the contraction of isolated uteri from pregnant mice were also measured, as was their production of prostaglandin E2 and prostaglandin F2α by an enzyme immunoassay method.

Results. Lipopolysaccharide augmented the in situ uterine contractions in both pregnant and non-pregnant rabbits, as well as the in vitro contractions of isolated uteri from pregnant mice. Lipopolysaccharide also increased the uterine prostaglandin production. Urinary trypsin inhibitor inhibited significantly the lipopolysaccharide-induced uterine contractions and the prostaglandin production.

Conclusions. Lipopolysaccharide enhanced uterine contractions through, at least partly, a direct mechanism via uterine prostaglandin production, which action could explain the onset of preterm delhery due to intrauterine bacterial infection. As urinary trypsin inhibitor suppressed the lipopolysaccharide-induced uterine contractions, this inhibitor may be a hopeful candidate of a drug for prevention of preterm delivery.