The female reproductive system has three isoforms
of NOS and synthesizes NO using L-arginine.
Accordingly, NO has a role in the physiology of
reproduction
15. NO induces smooth muscle relaxation
by binding to soluble guanylate cyclase and increasing
cyclic guanosine monophosphate (cGMP) concentrations
3. The contractility of the uterus may be inhibited by NO
until the end of the normal gestation period. However, an
increase in cervix NOS enzymes at the end of the normal
gestation period leads to an increase in NO
concentrations. Thus, increased NO concentrations in
the cervix may help dilatation of the cervix
4.
Contractility of the uterus is considered to have a role in
cervical dilatation
16.
Previous studies have demonstrated an increase in
uterine NO production during pregnancy and a decrease
at term17-21. Sladek et al.17 reported that NOS
activity is high during rabbit pregnancy and progressively
decreases by 80% in decidua during the last four days of
gestation. Similarly, Buhimschi et al.4 reported that
uterine NO synthesis increases during gestation and
decreases at term conversely, cervical NO synthesis is
low in the pregnant animals on days 18–22 of gestation
but significantly increases at the end of the normal
gestation period. Also, Ali et al.22 suggested that
uterine iNOS mRNA is increased during pregnancy and
decreased at term in contrast, cervical iNOS mRNA is
low until delivery (day 22) when it increases and is
significantly increased during labor. In addtion, 3 h after
injection with the antiprogestin onapristone, iNOS mRNA
is significantly decreased in the uterus (~45%) and
increased in the cervix (~245%) when compared with
controls, and the changes in bNOS and eNOS during
gestation are not significant compared to those in the
iNOS. As a result, the changes in iNOS mRNA at the end
of pregnancy may play a role in cervical ripening.
Furthermore, the changes in iNOS can be resembled
during preterm labor following antiprogesterone
treatment22. Momohara et al.23 reported that NO
per se does not directly cause the myometrial relaxation,
but NO plays an important role in regulation of
myometrium contractions during gestation by modulating
ET-1 (endothelin-1) production in the myometrium, and
increased endogenous NOS inhibitors and ET-1
production in the myometrium increase myometrial
contractions at term and after delivery.
Dilatation of the cervix is important in the regulation
of normal labor. Cervical structure is thought to be
changed at this time, with increased tissue water content,
alteration of matrix glycosaminoglycans, and separation
of the connective tissue structure24. NO exhibits an
ultimate metabolic pathway of cervical ripening. It
induces local vasodilatation and increases vascular
permeability, leukocyte infiltration, and matrix
metalloproteinase and other mechanisms, concert with
PGE225. The outcome of pregnancy is provided by the
suitable timing of cervical ripening. A cervical ripening
failure at the end of a normal pregnancy period may cause dysfunctional labor26. Shi et al.16 showed
that treatment with NOS inhibitors suppresses ripening
whereas NO donors and prostaglandins speed up it; NO
and prostaglandins play important roles in the
arrangement of cervical ripening. This study showed an
important difference between the plasma NO levels of
cows with dystocia and those with normal calving
(P<0.05).
Hirata et al.27 reported that arginase activity was
significantly decreased at the 7th, 14th and 21st day of
gestation; on the contrary, the enzyme activity significantly increased at the end of the normal gestation
period, and arginase activity in the myometrium had a
nonsignificant higher value after delivery. Increased
arginase activity at the end of the normal gestation
period would be involved in increasing myometrial
contractions27. In this study, it was found that the
erythrocyte arginase activity in cows normally calving
was significantly increased compared to that in cows with
dystocia (P<0.01). It was concluded that the lower
erythrocyte arginase activity and higher plasma NO level
in cows might play a role in dystocia.
)
