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PubMed1999

Expression of connexin-26, -32, and -43 gap junction proteins in the porcine cervix and uterus during pregnancy and relaxin-induced growth.

Connexin (CX) proteins participate in growth, differentiation, and tissue remodeling. Relaxin-stimulated reproductive tissue growth and remodeling may be facilitated by enhanced intracellular communication. This study was an examination of the effects of relaxin in vivo on expression of CX-26, CX-32, and CX-43 in the cervix and uterus of prepubertal pigs. In addition, expression of these proteins was monitored in the sow uterus during pregnancy. Relaxin was administered to prepubertal gilts every 6 h for 54 h. CX expression was characterized by immunoblotting and localized by immunofluorescence. Significant increases in all three CXs were observed in the cervix following relaxin treatment (P < 0.05). Uterine CX proteins were also significantly higher (P < 0.05) in relaxin-treated animals compared to controls. The CX protein level in relaxin-treated animals was similar to that observed during the second half of pregnancy, but below levels found in mature, nonpregnant sows. This is the first evidence for specific CX expression in the porcine cervix, and the first study to show that relaxin increases the expression of CX proteins in the porcine uterus and cervix. The data show that CX proteins are differentially regulated in the uterus of the pig during pregnancy. These data support a role for CX-mediated communication during relaxin-induced reproductive tissue growth and remodeling.

Animals↗
PubMed1996

Differential expression of cyclooxygenase-1 and -2 proteins in rat uterus and cervix during the estrous cycle, pregnancy, labor and in myometrial cells.

The synthesis of prostaglandins in the uterus at term are modulated by two isoforms of the enzyme cyclooxygenase (COX): constitutive COX-1 and inducible COX-2. This study aims to characterize the expression of the protein for COX-1 and -2 in the rat uterus and cervix during the estrous cycle, pregnancy, and labor, and in cultured myometrial cells. Western immunoblotting of proteins was performed and quantitation of protein was obtained densitometrically. Results indicate: 1) the rat uteri, cervix, and isolated myometrial cells express both COX-1 and COX-2 proteins, 2) during pregnancy, both COX-1 and -2 increase, with a dramatic increase at parturition (250%-280%), 3) a 2-fold increase of cervical COX-2 is seen at spontaneous labor, 4) during proestrus and estrus, uterine expression of COX-2 is elevated, 5) both COX-1 and -2 were expressed by rat myometrial cells and treatment with IL-1 beta (10 ng/mL) produced a significant increase in COX-2, and 6) immunocytochemical studies show that both COX-1 and -2 were primarily localized to the epithelial cells of the endometrium and smooth muscle cells in the circular layers of the myometrium in the uterus and to the epithelial cells and smooth muscle cells in the cervix. Thus, we propose that increased expression of COX-2 may be involved at term in increased uterine contractility and cervical ripening.

Animals↗
PubMed2001

Changes in the weight, collagen concentration and content of the uterus and cervix of the ewe during pregnancy.

The dry and wet weights of the uterus (caruncular and intercaruncular areas) and cervix were measured in non-pregnant (n = 5) and pregnant (n = 25) ewes post mortem; for the latter, five were obtained for each of the 5 months of gestation. The total collagen tissue content was measured in both areas of the uterus and cervix by hydroxyproline analysis and image analysis of Haematoxylin-Van Gieson stained tissue sections. Both wet and dry uterine weights increased significantly with gestational age (P < 0.001). The water content of uterine and cervical tissue remained constant, at between 83 per cent to 85 per cent and 76 per cent to 80 per cent, respectively. There was a close correlation between the two methods used to determine the collagen content (r = 0.96, P < 0.001), and between the increasing weight of the uterus during pregnancy and the total collagen content of tissues (r = 0.97, P < 0.001). At all stages, the total collagen content of the cervix [mean (SEM) 96.2 (5.4) mg g(-1)] was significantly greater (P < 0.001) than that of the caruncular mean [mean (SEM) 24.3 (1.4) mg g(-1)], and the intercaruncular areas [mean (SEM) 29.0 (1.0) mg g(-1)]. The changes in uterine and cervical weights and collagen content of the tissues were similar to those reported in other related species.

Animals↗
PubMed1998

Sympathetic innervation of the upper and lower regions of the uterus and cervix in the rat have different origins and routes.

The origins and routes of the postganglionic sympathetic nerve supply to the upper and lower uterus and to the cervix were investigated in the rat by using denervation procedures combined with immunohistochemistry and retrograde tracing. The sympathetic nerve fibers of the upper part of the uterus arise from the ovarian plexus nerve. They mainly originate (90%) from neurons of the suprarenal ganglia (SRG) and of the T10 to L3 ganglia of the paravertebral sympathetic chain. Fluoro-Gold injections into different regions of the upper uterus showed that the SRG neurons mainly provide innervation to the tubal extremity (52%) rather than to the uterine portion below this area (26%). Very few neurons of the celiac ganglion or the aorticorenal ganglia participated in this innervation. Most of the sympathetic innervation of the lower uterus and the cervix (90%) originates from neurons of the paravertebral ganglia T13 to S2, principally at the L2-L4 levels. By using immunocytochemistry, we show that very few tyrosine hydroxylase-positive neurons of the pelvic plexus project to these areas, where they represent only 3% of the sympathetic nerve supply. Again, very few neurons of the inferior mesenteric ganglion (IMG) supply the lower uterus and the cervix. The comparison between retrograde tracing experiments in intact animals and after the removal of the IMG shows that very few sympathetic postganglionic axons from the paravertebral chain pass through the IMG to reach the lower uterus and the cervix. In contrast, these axons mainly project to splanchnic nerves bypassing the IMG to connect with the hypogastric nerves. In addition, some axons supplying the lower uterus follow the superior vesical arteries and then reach the organ. Taken together, these results show that the upper region of the uterus receives a sympathetic innervation that is different in origin and route from that of the lower uterus and the cervix. Such a marked region-specific innervation suggests that nerve control of the myometrial activity may be functionally different between the oviduct and the cervical ends of the uterus.

Animals↗
PubMed2003

The influence of ovariectomy with or without estrogen replacement on responses of rat gracile nucleus neurons to stimulation of hindquarter skin and pelvic viscera.

Responses of neurons in the gracile nucleus (NG) of female rats to tactile and visceral stimulation change across the estrous cycle [J. Neurosci. 20 (2000) 7722]. To investigate estrogen's role in these changes, responses of NG neurons to tactile and visceral stimuli were examined in three groups: ovariectomized (OVX), OVX with estrogen replacement (OVX+E2), or sham OVX (tested in diestrus; shamOVX-D). The stimuli were: gentle brushing of hindquarter skin, pressure on the cervix, and distention of the uterus, vagina, or colon. After OVX, the magnitude of multi-unit responses to brushing the perineum, hip and tail, but not the foot and leg, were significantly reduced relative to shamOVX-D. OVX+E2 restored this magnitude to the same level as shamOVX-D, but not, as expected, to levels as large as previously observed in proestrus. After OVX, responses of single neurons to stimulation of the uterus, cervix, and colon were more likely to be excitatory (versus inhibitory) than they had been in cycling rats in proestrus (uterus, cervix) or diestrus (colon); OVX+E2 did not restore the inhibitory responses. In contrast, whereas all responses to vaginal distention after OVX were also excitatory, OVX+E2 in this case significantly restored the inhibitory responses. These findings provide further support for the conclusion that response characteristics of NG neurons are influenced by the rat's hormonal milieu, but also indicate that the influences are not a simple reflection of estrogen levels. The findings further suggest that NG is a component of neural systems that contribute to both reproductive behaviors and vaginal nociception.

Animals↗
PubMed1999

Macrophage trafficking in the uterus and cervix precedes parturition in the mouse.

Immune activation is implicated in the etiology of preterm labor, but little is known about macrophage number or distribution in the uterus or cervix at term. This study tested the hypothesis that macrophages migrate into the reproductive tract before the onset of parturition. Paraffin-embedded sections from the mid-uterine horn and cervix of C3/HeN mice on Days 15 and 18 of pregnancy, the day of birth (Day 19), and 1 day postpartum were stained with a pan-macrophage marker to analyze cell numbers and distribution. During pregnancy, uterine macrophages were dispersed in endometrium, usually associated with vasculature and subluminal epithelium. In myometrium, macrophages were clustered in stromal connective tissue; near term and postpartum, cells appeared to surround the muscle bundles. Total macrophage numbers were increased on Day 15 relative to those in nonpregnant controls, declined before birth, and increased postpartum. In the cervix, macrophages congregated in subepithelium, often perivascular or near ganglia. Macrophage numbers in the cervix peaked on Day 18, then declined to nonpregnant levels by the day after birth. Thus, macrophage numbers in the uterus were inversely related to those in the cervix. These findings raise the possibility that macrophages and their products may be involved in uterine contractility and cervical remodeling during the processes of parturition.

Animals↗
PubMed1997

Changes in expression of the nitric oxide synthase isoforms in rat uterus and cervix during pregnancy and parturition.

Nitric oxide (NO) is considered to be an important local mediator that suppresses uterine contractility in rats and rabbits during pregnancy until term. The aim of this study was to investigate the mRNA concentrations for the three isoforms of nitric oxide synthase (NOS) in rat uterus and cervix and to determine whether alterations occur in association with labour at term or preterm. RNA was isolated from full thickness uterine and cervical tissues from pregnant rats at various times during gestation, during labour at term or preterm and post partum. RNA was analysed using reverse transcription-polymerase chain reaction (RT-PCR) with a single set of amplimers specifically designed to detect all three isoforms of NOS. Three distinct PCR products were detected which corresponded to the expected sizes for endothelial (e)NOS, neuronal (b)NOS and inducible (i)NOS products (805, 521 and 428 bp respectively). In all tissues, the 428 bp product predominated and sequence analysis revealed this to be iNOS mRNA with a very close homology (97%) to the published sequence of rat iNOS. Densitometric analysis showed that uterine iNOS mRNA was increased during pregnancy, decreased on day 22 before labour and decreased further during labour at term. In contrast, cervical iNOS mRNA was low until delivery (day 22) when it increased and was dramatically elevated during labour. Similarly, 3 h after injection with the antiprogestin onapristone, iNOS mRNA was significantly decreased in the uterus (approximately 45%) and increased in the cervix (approximately 245%) when compared with controls. The mRNAs to bNOS and eNOS (corresponding to the 521 and 805 bp bands) were generally greatly reduced in quantity compared with the 428 bp product. The changes in these constitutive isoforms during gestation were minor compared with those in the inducible isoform. We conclude that the iNOS transcript is the most abundant NOS mRNA in the uterus as well as in the cervix and this probably indicates that the inducible NOS is the main isoform present in these tissues. The changes in iNOS mRNA at the end of pregnancy may play a role in the initiation of term labour and cervical ripening. Furthermore, the changes in expression of iNOS can be mimicked during preterm labour following antiprogesterone treatment, and may suggest that progesterone differentially controls the expression of iNOS in the uterus and cervix.

Animals↗
PubMed1984

Pattern of electrical activity of the ovine uterus and cervix from mating to parturition.

The electrical activity of the uterus, greater curvature and lesser curvature, and of the cervix were recorded throughout several oestrous cycles, matings and the entire course of pregnancy in a set of ewes. In cyclic ewes, all electrode sites were active during the periovulatory period, but during the luteal phase only the cervix and lesser curvature continued to present regular activity, i.e. episodes of 6-8 min duration. Matings failed to disrupt the oestrous activity pattern in 5 out of 6 ewes. During the subsequent pregnancy in 4 ewes, activity, when present, consisted of the cyclic occurrence of regular activity episodes in the gravid horn(s) (greater curvature) and in the cervix (and lesser curvature in 1 ewe). Three phases were recognized on the basis of the activity of the greater curvature of the gravid horn(s). The first phase corresponded to quiescence of the horn from Day 5 (Day 0 = mating) to about Day 41. The second phase was marked by the sudden onset of regular activity of the uterus; frequency rapidly increased and maximal values were reached around Day 49, after which frequency progressively decreased until around Day 66. The third phase was characterized by a steady state in genital tract activity until the peripartum period. The cervix and lesser curvature activity followed an almost similar development of regular activity episodes with only slight time differences.

Animals↗
PubMed1982

Localization of relaxin binding sites in the rat uterus and cervix by autoradiography.

125I-labeled porcine relaxin was injected into 27-day-old rats treated with pregnant mare's serum gonadotropin (PMSG) and known target tissues for relaxin, the myometrium, endometrium and cervix, and putative control tissues, heart, thigh muscle and duodenum, examined for binding by autoradiography. Specific binding in the target tissues was demonstrated by simultaneous injection of excess unlabeled relaxin. Radioactivity was located and quantified by grain counts predominantly over the inner, circular muscle layer of the myometrium and the cervix and to a lesser extent over the outer longitudinal muscle layer of the myometrium and the endometrium. The route of injection, the circulation time, or counting grains in transverse or longitudinal sections of myometrium made little difference in these results. Ovariectomy decreased, but not significantly, the grain count in all of the target tissues studied and estrogen treatment of ovariectomized animals restored the numbers of grains to approximately that of intact PMSG-treated rats. The degree of binding of the cervix was approximately that of the circular myometrial muscle. This work confirms the presence of specific receptors for relaxin in the rat uterus and cervix of primed rats and it also suggests that the inhibitory action of relaxin upon the myometrium is primarily on the inner circular muscle layer.

Animals↗
PubMed2004

The diagnosis and reproductive outcome after surgical treatment of the complete septate uterus, duplicated cervix and vaginal septum.

OBJECTIVE: This study was undertaken to evaluate the diagnostic management and the reproductive outcome after surgical repair of a rare reproductive malformation. STUDY DESIGN: Sixteen women with a complete septate uterus, double cervix, and a longitudinal vaginal septum were referred for evaluation. Presenting complaints were chiefly pregnancy loss in parous women (n=9) and dyspareunia in nulligravid women (n=7). The combination of hysterosalpingography, ultrasonography, and/or magnetic resonance imaging was used to correctly identify the anomaly in 15 of the 16 cases. Both hysteroscopic (n=11) and transabdominal (n=5) surgical techniques were used to repair the uterine septum. RESULTS: In no case was the correct diagnosis made before referral; the uterus didelphys was the most common misdiagnosis. The preoperative pregnancy loss was 81%. Postoperatively, 12 women conceived for a total of 17 pregnancies; there were 14 term live births or ongoing pregnancies in the third trimester (82%), with a first trimester spontaneous abortion rate of 18%. In 9 women who conceived after hysteroscopic surgery, term live births occurred in 9 of 12 (75%) conceptions. A modified Tompkins metroplasty was performed in 5 women with subsequent term live births or ongoing third trimester pregnancies in 5 of 5 (100%) patients. CONCLUSION: The identification of a duplicated cervix and a vaginal septum is consistent with several uterine malformations, which leads to frequent misdiagnosis and errors in management. Significant pregnancy wastage, obstetric complications, and dyspareunia are common, and surgical treatment is therefore advisable. Making the best choice between hysteroscopic or transabdominal metroplasty depends on the anatomic features of the cervix and the uterine cavity, but optimal patient management requires familiarity with both techniques.

Abnormalities, Multiple↗
PubMed1998

Role of nitric oxide in the uterus and cervix: implications for the management of labor.

The results of our experimental studies indicate that that parturition is composed principally of two major phases, a relatively long conditioning (preparatory) phase followed by a short and probably irreversible active labor phase. The major events of conditioning phase are: (i) the progression of uterine contractility from an inactive to a vigorously active state, (ii) cervical ripening, and (iii) activation of fetal membranes. Our experimental and molecular studies indicate that nitric oxide (NO) is an important element in controlling uterine and cervical functions during the transition from pregnancy to the conditioning phase of labor. These studies show that NO acts in concert with progesterone to regulate uterine quiescence and cervical rigidity. In the rat uterus and cervix NO is produced mainly by the cytokine-inducible NO synthase (iNOS) which expression is gestationally-regulated and progesterone-dependent. During pregnancy iNOS expression is up-regulated in the uterus and down-regulated in the cervix. Opposite changes occur during term and antiprogestin-induced preterm labor. Our studies with NOS-inhibitors and NO donors suggest that in the uterus a decrease in NO production contributes to the initiation of labor, whereas in the cervix NO acts as a final metabolic mediator of cervical ripening. The evidence also indicates that NO donors have therapeutic potential as tocolytic agents. On the other hand, locally applied NO donors can be used to induce cervical ripening. In addition iNOS, may represent a new target for novel therapeutic agents capable of promoting or inhibiting uterine of both contractility and cervical ripening. There is an urgent need for controlled studies demonstrating clinical efficacy and safety of NO donors in obstetrics.

Animals↗
PubMed1986

Short-term in vitro chemosensitivity testing of tumours of the ovary, cervix and uterus. Measurement of DNA metabolism by 3H thymidine incorporation.

A 3-hour biochemical assay was chosen in the present prospective study to determine the in vitro chemosensitivity of tumours of the ovary, cervix and uterus. The basis of the assay was to determine the ability of a panel of cytotoxic drugs to inhibit the proliferative activity of tumour cells in culture, using 3H thymidine as a precursor of DNA synthesis. We found variability in the in vitro responses of individual tumours to the 4 drugs (cisplatin, adriamycin, melphalan, methotrexate). In ovarian cancer, cisplatin and adriamycin produced the best inhibitory effects; serous cystadenocarcinomas were most frequently inhibited by cisplatin, whilst undifferentiated carcinomas were more affected by adriamycin. Only 14% of tumours were sensitive to all 4 drugs. We found a good correlation between in vitro results and in vivo response in the medium term. For cisplatin, the predictive accuracy was 85% for 'sensitive' tumours and 72% for 'resistant' tumours. These findings should increase our confidence in the test as a new aid to planning of chemotherapeutic strategies.

Antineoplastic Agents↗
PubMed1999

Vagal afferents from the uterus and cervix provide direct connections to the brainstem.

Previous anatomical studies demonstrated vagal innervation to the ovary and distal colon and suggested the vagus nerve has uterine inputs. Recent behavioral and physiological evidence indicated that the vagus nerves conduct sensory information from the uterus to the brainstem. The present study was undertaken to identify vagal sensory connections to the uterus. Retrograde tracers, Fluorogold and pseudorabies virus were injected into the uterus and cervix. DiI, an anterograde tracer, was injected into the nodose ganglia. Neurectomies involving the pelvic, hypogastric, ovarian and abdominal vagus nerves were performed, and then uterine whole-mounts examined for sensory nerves containing calcitonin gene-related peptide. Nodose ganglia and caudal brainstem sections were examined for the presence of estrogen receptor-containing neurons in "vagal locales." Labeling of uterine-related neurons in the nodose ganglia (Fluorogold and pseudorabies virus) and in the brainstem nuclei (pseudorabies virus) was obtained. DiI-labeled nerve fibers occurred near uterine horn and uterine cervical blood vessels, in the myometrium, and in paracervical ganglia. Rats with vagal, pelvic, hypogastric and ovarian neurectomies exhibited a marked decrease in calcitonin gene-related peptide-immunoreactive nerves in the uterus relative to rats with pelvic, hypogastric, and ovarian neurectomies with intact vagus nerves. Neurons in the nodose ganglia and nucleus tractus solitarius were immunoreactive for estrogen receptors. These results demonstrated: (1) the vagus nerves serve as connections between the uterus and CNS, (2) the nodose ganglia contain uterine-related vagal afferent neuron cell bodies, and (3) neurons in vagal locales contain estrogen receptors.

Animals↗
PubMed1989

[Reoxygenation of tumors of the uterine cervix during combined radiotherapy using low dose gamma-neutron irradiation with californium-252].

A polarographic method was used to follow the changes in oxygenation of a tumour of uterus cervix after intracavital irradiation by 252Cf by a physical dose of 2 Gy, applied at the beginning of a therapeutic cycle of combined radiotherapy. The results reached are compared with the results of tumour oxygenation in the course of a conventional therapeutic procedure. It has become apparent that even after the irradiation of a tumour of uterus cervix by a small dose of gamma-neutron radiation with 252Cf there is, beginning with 2nd week of therapy, a significant reoxygenation of the tumour population. The changes of oxygenation after a conventional irradiation have been less marked and reached, in the 4th week of therapy, only marginally significant increase. Differences in reoxygenation of tumours of uterus cervix were confirmed by analysis of the oxygen test. The importance of tumour reoxygenation after the application of 252Cf source of radiation for facilitation of its regression in a combined treatment with Californium-252 and gamma irradiation is discussed.

Brachytherapy↗
PubMed1975

[The detection of the carcinoma in situ of the cervix of the uterus and of the invasive carcinoma of the cervix of the uterus (author's transl)].

Report of the detection of 203 cases (87 of a carcinoma in situ of the cervix of the uterus, 116 of carcinoma of the uterus) out of 7769 cytologically examined patients at the ob.-gyn. deptm. of the Hospital Vienna-Lainz (Austria). The accuracy of cytology with respect to the detection of the carcinoma of the cervix: 95%. The importance of a gynecological examination performed at least once a year together with a cytological test and the examination of the breast is hereby stressed.

Adult↗