Human Reproduction, Vol 12, 2093-2101, Copyright © 1997 by Oxford University Press
K Chwalisz, S Shao-Qing, RE Garfield and HM Beier
In humans cervical ripening is an inflammatory reaction accompanied by an
infiltration of white blood cells and the remodelling of the extracellular
matrix. Similar changes occur in guinea-pigs during cervical ripening.
Nitric oxide (NO) is thought to be important in the maintenance of
pregnancy because it is synthesized by the uterus and inhibits
contractility. Previous studies in rats also demonstrated that an NO
generating system is present in the cervix and is up-regulated during
labour. We studied the local effect of the NO donor sodium nitroprusside
(SNP) on cervical ripening in guinea-pigs during advanced pregnancy. SNP (5
mg/injection) was administered into the cervical canal in 0.2 ml
phosphate-buffered saline containing 3% hydroxycellulose twice a day either
for 1 [on day 42 post coitum (p.c.)] or 2 consecutive days (days 42-43
p.c.; term day 67 + 3 p.c.). The effects were assessed 24 h after treatment
by both extensibility measurements (force resistance to incremental
stretch) and morphological evaluation (light and electron microscopy after
in-situ fixation). The control animals were treated with the vehicle. In
another experiment, the guinea-pigs were subcutaneously (s.c.) treated on
day 43 p.c. with either the progesterone antagonist onapristone (3 and 10
mg/animal s.c.) or with prostaglandin E2 (PGE2) (1 and 3 mg/animal s.c.)
and the PGE2 analogue sulprostone (0.03 and 0.1 mg/animal s.c.). The
cervical extensibility was measured 24 h later. One-day SNP treatment
tended to reduce cervical resistance, but not significantly, whereas 2 day
treatment with SNP led to a significant increase in cervical extensiblity
(P < 0.05) with little effect on cervical dilatation (indirect evidence
of the absence of uterine contractions). The effects on cervical resistance
were comparable to those achieved with 10 mg onapristone and high-dose
prostaglandins (PG)s (3 mg PGE2 and 0.1 mg sulprostone) treatment. An
electron microscope study of the SNP-treated animals revealed a dissolution
of collagen fibres, stromal oedema, arterial dilatation, and the
infiltration of macrophages, lymphocytes and granulocytes. Numerous mast
cells were also present. The morphological effects of SNP were similar to
those observed during normal cervical ripening at term. We conclude that
the local application of a NO donor effectively induces cervical ripening
without inducing labour in pregnant guinea-pigs.
ARTICLES
Cervical ripening in guinea-pigs after a local application of nitric oxide
Research Laboratories of Schering AG, Berlin, Germany.
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