Nitric oxide (NO) has emerged as one of several important intraovarian regulatory factors. In particular, NO has been implicated in the processes of ovulation and atresia-related apoptosis. The aim of the present study was to investigate the presence and distribution of the NO-generating nitric oxide synthase (NOS) enzymes in the ovary during follicular development, ovulation and luteal formation of the equine chorionic gonadotrophin (ECG)/human chorionic gonadotrophin (HCG)-primed rat. NADPH diaphorase activity was used as a histochemical marker for NOS within the ovary. Diaphorase reactivity was most abundant in the stroma (S) of the ovary and in the theca (T) layer of the follicle. In luteinized ovaries, weaker diaphorase reactivity was present within the corpora lutea (CL). Two different isoforms of NOS, the constitutively expressed endothelial NOS (eNOS) and the inducible isoform of NOS (iNOS), were immunolocalized in ovaries of immature rats and in ECG/HCG-primed rats during the periovulatory period from HCG injection until 2 days after ovulation. In addition, ovarian concentrations of eNOS and iNOS were quantified by immunoblotting. Immunoblotting with a monoclonal anti-eNOS antibody demonstrated the presence of eNOS mainly in the residual ovary (ROV) during the periovulatory period. In luteinized ovaries, higher concentrations of eNOS were seen in CL, while those in the ROV at this stage were lower than in the periovulatory ovary. Immature ovaries contained diminutive amounts of eNOS, detectable mostly in the ROV compartment. In contrast, iNOS was barely detectable during follicular development to the preovulatory stage. A slight elevation of iNOS was observed in the granulosa cells at 6 h after the HCG injection. The levels of iNOS during the luteal phase were also low. Immunohistochemical analysis using polyclonal eNOS and iNOS antibodies revealed the localization of these two isoforms primarily in the S and the T of the periovulatory ovary. In luteinized ovaries, positive immunoreactivity was also seen within the CL. With a monoclonal antibody against eNOS, intense immunoreactivity was observed in the S, T and within CL. There was a particularly strong staining in blood vessels. These data demonstrate the presence of an intraovarian NO-generating system. The localization of this system to the S, T and CL suggests a role for NO in the ovulatory process and in the regulation of CL function.

An ovary with a mature cystic teratoma which was autoamputated into the cul-de-sac and confirmed by laparoscopy is described. A 24-year-old woman with a history of chronic pelvic pain for 5 years presented with left abdominal pain. Magnetic resonance imaging revealed a left ovarian mass of 5 cm in diameter. The pain was relieved spontaneously after a few weeks. Laparoscopy was performed 5 months later. The mass was identified in the cul-de-sac partly enveloped in the omentum without any ligamentous or direct connection with the pelvic organs. There was no left ovary in its proper anatomical location. Histopathologic study revealed a mature cystic teratoma with viable ovarian tissue. These findings suggested autoamputation of the ovary either by inflammation or torsion, which is one of the mechanisms for the formation of an ectopic ovary.

Two isoforms of prostaglandin G/H synthase, PGS-1 and PGS-2, catalyze the formation of prostaglandins (PG). Nonselective PGS inhibitors, e.g., indomethacin, reduce the number of ovulations and PG levels in many animal models. This study evaluated the effects of the selective PGS-2 inhibitor NS-398, compared to indomethacin, on ovulation number and on PG and steroid production both in vivo and in vitro in the rat. NS-398 reduced the synthesis of PGE2 in isolated, LH-stimulated preovulatory follicles incubated in vitro. The inhibition by NS-398 was similar to that of indomethacin. Maximal inhibition was noted from 0.1 microM. Neither progesterone nor cAMP production was affected by NS-398 or indomethacin. The effect of in vivo administration of NS-398 (1, 3, or 10 mg/kg BW, s. c.) to proestrous rats 1 h after the injection of an ovulatory dose of hCG was monitored in follicles extirpated 10 h after hCG. These follicles were incubated in vitro, and NS-398 dose-dependently reduced PGE2 production. The synthesis of cAMP and progesterone was not altered. In separate experiments, the same doses of NS-398 were injected to determine their effect on ovulation in vivo. The number of ovulations was decreased by the highest dose of NS-398. In the in vitro ovarian perfusion model, NS-398 (10 microM) reduced the number of ovulations initiated by LH and isobutylmethylxanthine. Lower doses of NS-398 (0.1 and 1 microM) were less effective. The production of prostanoids (PGE2, PGF2alpha, and 6-keto-PGF1alpha) was reduced in a dose-dependent manner by NS-398. The secretion of steroids was not affected. This study demonstrates that selective inhibition of PGS-2 by NS-398 reduces LH/hCG-stimulated production of prostanoids and the number of ovulations both in vivo and in vitro. These results provide direct evidence to strengthen the role of the inducible, granulosa cell-expressed PGS-2 as one of the key regulators in the ovulatory process and also document that the elevated and perhaps sustained levels of PG are obligatory for ovulation.

There have been few reports on postpartum changes in the uterus during the three months after delivery. The aim of this study was to evaluate uterine morphological changes in women after vaginal delivery (n=262-351) and in women after cesarean section (n=64-82) and to evaluate the relation between breast-feeding and parity, and uterine involution at 1 and 3 months postpartum measured by vaginal ultrasonography. There were no significant differences in parity between the vaginal delivery group and the cesarean section group. The length of the uterus at one month (7.93+/-1.16 cm, mean+/-SD) and, three months (7.03+/-1.19 cm) and the width of the uterus at three months (3.83+/-0.94 cm) after delivery in the cesarean section group were greater than in the transvaginal group (7.64+/-1.03 cm, 6.65+/-0.99 cm, 3.57+/-0.62 cm, respectively). Increasing maternal parity was associated slightly with larger uterine size at one month post partum. The length of the uterus of women with a breast-feeding rate of 80% or more per day was 6.35+/-0.85 cm, and shorter than in women with a rate of 20% or less 7.03+/-1.04 cm, at three months after delivery. The width of the uterine body of women with a breast-feeding rate of 80% or more per day was 3.32+/-0.45 cm, and shorter than in women with a rate of 20% or less 3.87+/-0.66 cm, at 3 months after delivery. Stepwise regression and multiple regression analysis among parity, the history of cesarean section, the breast-feeding rate at one and three months after the delivery, and the restoration of the menses at three months after the delivery showed that the uterine size at one month after the delivery was related to the cesarean section and that the uterine size at three months after delivery was mostly related to the rate of breast-feeding. These results indicated that uterine involution was related to delivery mode at one and three months postpartum, feeding mode at three months postpartum, the menses restoration, and parity. The rate of breastfeeding was mostly related to the uterine size at three months postpartum.

These results indicate that menstrual blood loss does not affect the complete blood count and suggest that granulocyte-colony stimulating factor plays and important role in the mechanism of ovulation.