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PubMed2006

Evaluation of effectiveness of prophylactic cerclage of a short cervix according to interleukin-8 in cervical mucus.

OBJECTIVE: This study was undertaken to compare rates of preterm delivery according to cervical mucus interleukin-8 (IL-8) among women who underwent cerclage because of a short cervix. STUDY DESIGN: This retrospective study included 16,508 patients whose cervical length and cervical mucus IL-8 concentrations were measured between 20 and 24 weeks. A short cervix was defined by a length of 25 mm or less, whereas IL-8 concentrations exceeding 360 ng/mL were considered high. Whether to perform cerclage was decided by clinicians without consideration of IL-8 concentrations. RESULTS: Among all subjects, a significantly smaller percentage of subjects avoided delivery before 37 weeks when cervical mucus IL-8 was elevated (P = .0302) or the cervix was short (P < .0001). Among patients with a short cervix, preterm delivery was more likely when cervical mucus IL-8 was elevated. Overall, risk of preterm delivery in patients with a short cervix did not differ between those undergoing and not undergoing cerclage. However, among patients with a short cervix, those with normal IL-8 concentrations in cervical mucus were less likely to have preterm delivery if they underwent cerclage (before 37 weeks, 33% vs 54.5%, P = .01; before 34 weeks, 4% vs 13.6%, P = .03). In contrast, when cervical mucus IL-8 was high, delivery before 37 weeks was more likely with than without cerclage (78% vs 54.1%, P = .03). CONCLUSION: With normal cervical mucus IL-8, cerclage treatment for cervical shortening may reduce the rate of preterm delivery, but with elevated cervical mucus IL-8 cerclage may be harmful.

Cerclage, Cervical↗
PubMed1989

Human papillomavirus coinfections of the vulva and uterine cervix.

DNA filter in situ hybridisation (FISH) was used to determine the presence of human papillomavirus (HPV) genotypes 6/11, 16/18, and 31/33 in cell scrapes of the cervix and vulva of 128 women who had precancerous lesions and/or HPV infection of the cervix diagnosed by cytology, colposcopy, and histology. HPV-DNA was found in 87 (68%) vulval and 95 (74%) cervical cell scrapes, and in both the vulval and cervical scrapes of 73 (57%) women, but not in either the vulva or the cervix of 19 women (15%). Of the HPV-DNA-positive smears, the prevalence of the HPV types was 61% HPV 16/18, 14% HPV 6/11, 3% HPV 31/33, and 22% HPV 6/11 and 16/18. By contrast, HPV-DNA was not detected in the cervical smears of a control group of 35 women who were assessed to be free of cervical abnormalities by colposcopy and cytology. The epithelial response of the vulva and the cervix to application of 5% acetic acid was assessed by colposcopy and the results correlated with the presence of HPV genotypes. A possible or definite disorder of the cervix and vulva was detected by colposcopy in 95 (74%) and 96 (75%) of the 128 cases, respectively. The colposcopic assessment of the vulva was inconclusive in ten cases (8%), and only eight women (6%) were found to be free of both a vulval and cervical disorder. This study shows subclinical papillomavirus infections of the vulva frequently coexist with HPV infections and precancerous lesions of the cervix.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

A large proportion of afferent neurons innervating the uterine cervix of the cat contain VIP and other neuropeptides.

Axonal tracing techniques were used in combination with immunohistochemistry to examine the distribution of neuropeptides in afferent pathways from the uterine cervix of the cat. Primary afferent neurons innervating the uterine cervix were identified by axonal transport of the dye, fast blue, injected into the cervix. Fifteen to twenty-five days after the injection, dorsal root ganglia (L1-S3) were removed and incubated for 48-72 h in culture medium containing colchicine to increase the levels of peptides. Calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), leucine-enkephalin (LENK), somatostatin, substance P and vasoactive intenstinal polypeptide (VIP) were identified by use of indirect immunohistochemical techniques. Eighty-four percent of uterine cervix afferent neurons were identified in the sacral dorsal root ganglia (S1-S3), and 16% in the middle lumbar dorsal root ganglia (L3-L4). In sacral dorsal root ganglia, VIP was present in the highest percentage of dye-labeled cells (71%), CGRP in 42%, and substance P in 18% of the cells. CCK and LENK were present in 13% of the cells. In lumbar dorsal root ganglia, CGRP (51%) was most prominent peptide followed by VIP (34%), substance P (28%), LENK (17%) and CCK (13%). Somatostatin was present in the ganglia but did not occur in dye-labeled neurons. In conclusion, the uterine cervix of the cat receives a prominent VIP- and CGRP-containing afferent innervation. The percentage of neurons containing VIP is three to five times higher than the percentage of these neurons in afferent pathways to other pelvic organs. These observations coupled with the results of physiological studies suggest that VIP is an important transmitter in afferent pathways from the cervix.

Afferent Pathways↗
PubMed1989

Immunohistochemical investigations of steroid receptors in normal and neoplastic squamous epithelium of the uterine cervix.

The proliferation of squamous cells of the vagina and cervix uteri is induced by steroid hormones during the menstrual cycle. However, carcinoma of the cervix cannot be influenced by any hormone therapy. Forty-four different cervical specimens (different days in the menstrual cycle of healthy women and those with dysplastic lesions and carcinomas of the cervix) have been tested for estrogen (ER) and progesterone (PR) receptor protein content by means of immunohistochemistry. The ER content of the squamous epithelium depends upon the menstrual cycle: in the early proliferative phase cells of all layers are negative. In the midphase of proliferation the basal and parabasal layers become positive, and in the secretory phase positive cell nuclei can be found up to the superficial layers. A weak reaction to ER staining is found only in mild dysplastic lesions of the uterine cervix; severe dysplastic forms and invasive carcinomas were all negative. No positive PR was found in any squamous cell tissue. Stroma cells of the uterine cervix showed different straining intensity for ER and PR, regardless of the menstrual cycle. The loss of ER in the neoplastic cell could be an explanation for three clinical experiences: premenopausal patients have no tumor progression of the cervix uteri despite normal ovarian function; the duration of survival shows no relation to the receptor status of cervical carcinomas; and antihormonal treatment of cervical carcinomas produces no appreciable therapeutic success.

Adult↗
PubMed1994

Secretory proteins of the hamster cervix, uterus and oviduct: the effects of estradiol, progesterone and testosterone on the proteins secreted into the medium.

The present study was directed towards identification of proteins synthesized and secreted by the cervix, uterus and oviduct of immature hamsters and by the uterus of ovariectomized adult hamsters. Hamsters were treated with estradiol, progesterone or testosterone for 3 consecutive days after which the tissues were incubated in vitro and [35S]methionine labelled proteins were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The results demonstrate a great degree of similarity between the proteins synthesized and secreted by the cervix, uterus and oviduct of hamsters. Treatment of hamsters with estradiol consistently increased the synthesis of a 60 kDa protein in the cervix, uterus and oviduct. Further, estradiol also consistently suppressed the synthesis of a 14, 30 and 72 kDa protein in the uterus but not in the cervix and oviduct. In the cervix, in addition to the 60 kDa protein estradiol also induced the synthesis of two other proteins (a 38 and 56 kDa protein). Testosterone and progesterone did not induce or suppress the synthesis of the secretory proteins in the hamster cervix, uterus and oviduct. In hamster the 60 kDa protein could serve as a marker of gene expression following hormone action.

Animals↗
PubMed2003

The effects of pregnancy and estrogen on the expression of calcitonin gene-related peptide (CGRP) in the uterine cervix, dorsal root ganglia and spinal cord.

Before parturition the uterine cervix undergoes a ripening process ("softens" and dilates) to allow passage of the fetus at term. The exact mechanism(s) responsible for cervical ripening are unknown, though a role for peptidergic sensory neurons is emerging. Previous work demonstrated that administration of substance P (SP) to ovariectomized rats caused events associated with cervical ripening, that production of SP in cervix-related dorsal root ganglion (DRG) is estrogen responsive, and that release of SP from neurons terminating in the cervix and spinal cord peaks prior to parturition. The present study was designed to test the hypothesis that calcitonin gene-related peptide (CGRP), a neuropeptide co-stored with SP in many sensory neurons, undergoes changes with pregnancy and hormonal environment. Immunohistochemistry, in situ hybridization, reverse transcriptase-polymerase chain reaction (RT-PCR) and radioimmunoassay (RIA) were used to investigate CGRP in L6-S1 DRG, spinal cord and cervix during pregnancy and the role of estrogen in CGRP synthesis. CGRP-immunoreactive primary sensory neurons expressed estrogen receptors (ER-alpha and ER-beta). In the cervix, CGRP concentrations decreased, but in the L6-S1 DRG and the spinal cord segments, CGRP levels increased, with peak effects observed at day 20 of gestation. CGRP mRNA synthesis increased in DRG over pregnancy. Sensory neurons of ovariectomized rats treated with estrogen showed increased CGRP mRNA synthesis in a dose-related manner, an effect blocked by the ER antagonist ICI 182 780. From these results, we postulate that synthesis of CGRP in L6-S1 DRG and utilization in the cervix increase over pregnancy and this synthesis is the under influence of the estrogen-ER system. Collectively, these data are consistent with the hypothesis that CGRP plays a role in cervical ripening and, consequently in the birth process.

Animals↗
PubMed2001

Cell adhesion molecule expression in the cervix and myometrium during pregnancy and parturition.

OBJECTIVE: To determine the expression and localization of cell adhesion molecules intercellular adhesion molecule-1 (ICAM-1), E-selectin, platelet-endothelial cell adhesion molecule (PECAM), and vascular cell adhesion molecule (VCAM) in the cervix and myometrium during pregnancy and labor. METHODS: Biopsies of myometrium and cervix were obtained from non-pregnant women and from pregnant women before and after onset of spontaneous labor at term. Cell adhesion molecule mRNA expression was quantified using Northern blotting and cell adhesion molecule protein was localized using immunohistochemistry. RESULTS: ICAM-1 mRNA was upregulated in the cervix (10-fold increase, P <.01) and myometrium (10.5-fold increase, P <.01) during labor. ICAM-1 was localized in the vascular endothelium and in leukocytes in the cervix and myometrium from all three groups of women. VCAM mRNA was upregulated in the cervix (2.5-fold increase, P <.01) during pregnancy and there was no further change during labor. VCAM localized weakly to the vascular endothelium in cervical and myometrial biopsies from pregnant and non-pregnant women. PECAM mRNA was significantly upregulated in myometrium during pregnancy (ninefold increase, P <.01) and did not change with the onset of labor. PECAM localized to the vascular endothelium in all cervical and myometrial biopsies and was identified on leukocytes. There were no significant changes in E-selectin mRNA expression in either tissue with pregnancy or parturition. CONCLUSION: Cell adhesion molecule expression changes in human cervix and myometrium during pregnancy and parturition. At least part of these changes are attributable to expression by leukocytes infiltrating these tissues.

Adult↗
PubMed2003

Substance P in the uterine cervix, dorsal root ganglia and spinal cord during pregnancy and the effect of estrogen on SP synthesis.

Prior to parturition the non-pliable uterine cervix undergoes a ripening process ("softens" and dilates) to allow a timely passage of the fetus at term. The exact mechanism(s) triggering and involved in cervical ripening are unknown, though evidence for a role for sensory neurons and their contained neuropeptides is emerging. Moreover, an apparent increase in neuropeptide immunoreactive nerves occurs in the cervix during pregnancy, maternal serum estrogen levels rise at term and uterine cervix-related L6-S1 dorsal root ganglia (DRG) sensory neurons express estrogen receptor (ER) and neuropeptides. Thus, we sought to test the hypothesis that the neuropeptide substance P (SP) changes biosynthesis and release over pregnancy, that estrogen, acting via the ER pathway, increases synthesis of SP in DRG, and that SP is utilized in cervical ripening at late pregnancy. Using immunohistochemistry, in situ hybridization, reverse transcriptase-polymerase chain reaction (RT-PCR) and radioimmunoassay (RIA), we investigated coexpression of ER-alpha/beta and SP; differential expression of ER-alpha and -beta mRNA in DRG neurons; SP synthesis in DRG; and changes in SP concentration in the cervix, DRG and spinal cord over pregnancy. In addition, the effect of exogenous estrogen on SP synthesis in L6-S1 DRG of ovariectomized rats was examined. SP-immunoreactive neurons expressed ER-alpha and ER-beta. SP synthesis (expressed as beta-PPT mRNA label) was prominent in small DRG neurons. SP concentration increased in the L6-S1 DRG and spinal cord segments, with a peak at Day 20 of gestation, but decreased in the cervix during the first two trimesters, with a rise over the last trimester to Day 10 levels. SP and ER-alpha mRNA synthesis increased in DRG over pregnancy but ER-beta mRNA levels were largely unchanged. When ovariectomized rats were treated with exogenous estrogen, SP mRNA synthesis in the DRG increased in a dose-related manner, an effect blocked by ER blocker ICI 182 780. From these results, we postulate that synthesis of SP in L6-S1 DRG and utilization in the cervix increase over pregnancy and this synthesis is under influence of the estrogen-ER system, most likely ER-alpha. We postulate that SP may play a role in cervical ripening and, consequently in the birth process.

Animals↗
PubMed2005

[Early prophylactic cervical cerclage for hypoplastic cervix following exposure to DES in utero].

AIM: Presentation of a prophylactic cerclage technique, placed in the beginning of second trimester of the pregnancy, derived from McDonald cerclage and adapted to hypoplastic cervix following exposure to DES in utero. MATERIALS AND METHODS: Prospective study including 20 pregnant patients exposed to DES in utero and presenting a hypoplastic cervix. Study of the location of the cerclage tape in the cervix and of changes in cervical length (before and after cerclage) assessed by physical examination of the cervix and by transvaginal ultrasonography. RESULTS: The cervix was longer after cerclage as shown by physical examination and by ultrasound. The tape was localized near the internal cervical os, its posterior portion nearer the internal cervical os than its anterior portion. CONCLUSION: This easy-to-perform technique of cerclage of hypoplastic cervix allows the tape to be localized near the internal cervical os without colpotomy and without use of the transabdominal approach, while allowing vaginal delivery.

Cerclage, Cervical↗
PubMed1984

Studies on human uterine cervix and rat uterus using S-, X- and Q-band electron-spin-resonance spectroscopy.

In previous studies we have reported on the detection of a strong e.s.r. signal in samples of normal human cervix; the signal is much reduced or absent in samples of invasive cancer of the cervix. In order to identify the species responsible for the strong signal, we have used X-, S- and Q-band e.s.r. spectroscopy. The major signal that is detectable in ground-up samples of cervix preserved at -196 degrees C has features consistent with the presence of a peroxy free radical. Good agreement with the experimental findings was obtained by computer simulation, using values for the g-tensor of gx = 2.002, gy = 2.005 and gz = 2.036. The peroxy radical is produced on grinding the normal cervix samples to a powder under liquid N2, and appears to be formed by modification of a pre-existing oxygen-containing complex. Control experiments eliminated the possibility that the strong signals seen in frozen powders prepared from normal cervix were artefacts only of the grinding procedure. Experiments with rats in vivo and with cervix samples in vitro are consistent with the conclusion that the peroxy radical is formed by disturbing the cyclo-oxygenase system that is involved in prostaglandin synthesis.

Animals↗
PubMed2002

Transvaginal sonographic examination of the cervix in asymptomatic pregnant women: review of the literature.

Different strategies have been developed to refine the prediction of the risk of preterm delivery in asymptomatic patients. Transvaginal sonography has been used for this reason to measure and examine the length and shape of the cervix. In this review, we focus on clinical studies involving transvaginal sonographic assessment of the cervix in asymptomatic women at high risk of preterm delivery and in the general pregnant population. Three ultrasound signs are suggestive of cervical incompetence, namely, dilatation of the internal os, sacculation or prolapse of the membranes into the cervix (with shortening of the functional cervical length) either spontaneously or induced by transfundal pressure, and short cervix in the absence of uterine contractions. Transvaginal sonography has clearly demonstrated that cerclage leads to a measurable increase in cervical length which may contribute to the success of this procedure in reducing the risk of preterm delivery. Several non-randomized interventional studies among patients with cervical incompetence have been published. They have defined a new group of patients requiring cerclage when the women show progressive cervical modifications on transvaginal sonography, while in other studies, cerclage performed on the basis of cervical changes on transvaginal sonography did not prevent premature delivery. One prospective randomized trial in asymptomatic high-risk women has shown two benefits of cerclage following indications for transvaginal sonography: (1) it would generate fewer prophylactic cerclages in high-risk women; (2) therapeutic cerclage before 27 weeks may reduce the incidence of premature delivery before 34 weeks. The risk of preterm delivery is inversely correlated with cervical length. Routine transvaginal sonography of the cervix performed between 18 and 22 weeks can help identify patients at risk of preterm delivery. However, given the low prevalence of preterm births, screening would generate either a high false-positive rate or a low sensitivity. One non-randomized interventional study among patients with a short cervix on routine ultrasound examination found a lower risk of delivery before 32 weeks in the cerclage group than in the expectant management group. However, to date, there have been no prospective randomized trials in a general population. Although evidence is still lacking, there does appear to be a benefit in performing a cerclage rather than continuing with expectant management in cases with sonographic appearance of cervical incompetence in asymptomatic women at high risk of preterm delivery. Ultrasound can be offered to reduce the indications of cerclage for cases in which the situation is uncertain. Within the general obstetric population, transvaginal sonography might help in the selection of asymptomatic but high-risk women. However, the benefit associated with cerclage for sonographic indication has not been demonstrated.

Cervical Ripening↗
PubMedDate not supplied

[Quantitative ultrasonic tissue characterization of the cervix - A new predictor for prematurity?].

BACKGROUND: Since the incidence of premature delivery has remained constant for the last decade despite intensive safeguarding methods, the texture features of the uterine cervix were evaluated using quantitative sonographic gray level analysis at different gestational ages. MATERIALS AND METHODS: For this purpose, quantitative ultrasonic tissue densitometry of the uterine cervix was obtained from 30 asymptomatic female patients (group A, mean: 30,3 GA) and compared with values obtained from 16 symptomatic female patients (group B, mean: 29,5 GA) with uterine contractions and shortening of the cervix at similiar gestational ages. Once the two-dimensional transvaginal sonographic measurement of cervical length was completed, a region of interest of constant size was defined in the mid-section of the posterior wall, and the tissue-specific gray scale distribution was determined. RESULTS: Quantitative ultrasonic tissue characterization of uterine cervix was feasible in all 46 patients at all gestational ages. In patients with premature contractions and shortening of cervix the average gray scale values were found to be significantly reduced in comparison with those obtained from asymptomatic patients. These results showed good reproducibility and low intraobserver variability and were found to be independent of the measured cervical length. CONCLUSION: Our results prove that quantitative ultrasonic tissue characterization of the uterine cervix might serve as a new parameter for predicting premature delivery.

Adult↗
PubMed2006

[Grey-scale texture analysis of the cervix in pregnancy].

AIM: The measurement of the length of the cervix is just a method of routine, but the analysis of the grey-scale texture of the cervix represents a method poorly evaluated to date which may have the scope of improving the prediction of premature birth. Before it can be used for clinical purposes, the method must be standardised. METHODS: 66 patients were examined endosonographically. The analysis was done both visually and automatically, using a commercially available software. Inside a ROI (region of interest), we calculated the mean of the histogram, and homogeneity as well as contrast of the co-occurrence matrix of the grey-scale values. The influence of ultrasound wave propagation as well as location, extension and sound angle of the ROI were examined, and the results of the analysis performed by man and machine were compared. Additionally, we compared the textures of the inner and outer cervical os as well as the anterior and posterior lip of the cervix. RESULTS: As homogeneity and contrast were significantly influenced by the propagation of ultrasound waves, we developed a new angle-independent parameter combining the results of the 45 degrees and the 90 degrees calculation. Small changes in location, extension and sound angle of the ROI did not influence our results significantly. The texture analysis performed by the software was significantly better than the one performed by the examiner. The maximum of brightness was detected in the region of the internal os/anterior lip. Contrast as well as homogeneity showed significant differences between all parts of the cervix. CONCLUSION: The analysis of the grey-scale texture of the cervix can deliver clinically relevant results in the prediction of premature birth. The external influence on sound wave propagation as well as different locations inside the cervix must be taken into consideration.

Cervix Uteri↗
PubMed1985

[Use of a new vaginal suppository: prostaglandin E1 analog Gemeprost for cervix maturation prior to abortion in the 1st trimester].

This double-blind study is concerned with the efficacy and safety of a new prostaglandin E1-analogue (16,16'-dimethyl-trans-delta 2PGE1-methylester) (Gemeprost) (ONO-802), which was administered as a single 1 mg vaginal pessary three hours prior to legal abortion. The efficacy of the prostaglandin was assessed by the largest size of the dilator meeting no resistance when inserted in the cervical channel. Furthermore, the quality of the cervix and the effort needed for further dilatation was evaluated. The average size of the cervix prior to dilatation was found to be 10 mm, in comparison to only 7 mm in the placebo-group (p less than 0.001). 80% of the patients of the Gemeprost group did not need any further dilatation, i.e. the dilatation procedure of the cervix was easier than in the group without treatment (19%). The incidence of uterine pain was more frequent in the Gemeprost group (40%) than in the Placebo group (7%). Analgesics were not required. The frequency of gastrointestinal side effects was rare in the Gemeprost group (13%) and in the Placebo group (11%) compared with other prostaglandins. By the preoperative application of a new prostaglandin E1-analogue (1 mg) prior to vacuum aspiration in the first trimenon of pregnancy sufficient softening of the cervix and a dilatation of the cervix was achieved. It significantly reduces the need for further mechanical dilatation of the cervix as well as the force needed to perform this dilatation. These effects reduce the trauma associated with mechanical dilatation and therefore diminish the risk of subsequent complications.

Abortifacient Agents↗
PubMed2005

Uterine contractions in asymptomatic pregnant women with a short cervix on ultrasound.

OBJECTIVE: To estimate the incidence of uterine contractions in asymptomatic pregnant women with a short cervix on transvaginal ultrasound. METHODS: Asymptomatic women with a short cervix on transvaginal ultrasound between 14 and 23(6/7) weeks of pregnancy were instructed to undergo uterine monitoring immediately. Women without available tracings were excluded. Women with and without contractions were compared with regard to demographics, risk factors, and outcomes. RESULTS: One hundred and one women with a short cervix and available tracings were identified. Eighty-six (85%) had contractions and 15 (15%) did not have contractions immediately after identification of the short cervix. The median number of contractions per hour per woman was 4 (range 0-31). These two groups did not differ in demographics, risk factors, or outcomes, except for the fact that 33% of women with contractions versus 73% of women without uterine contractions had a prior second trimester loss (p = 0.004). CONCLUSIONS: In this study, 85% percent of pregnant women with a short cervix on transvaginal ultrasound between 14 and 24 weeks of pregnancy are having asymptomatic uterine contractions. This information is important for further investigation of the short cervix and preterm delivery.

Abortion, Spontaneous↗
PubMed1996

Differential regulation of nitric oxide in the rat uterus and cervix during pregnancy and labour.

The aim of this study was to determine if nitric oxide (NO) production and nitric oxide synthase (NOS) isoforms change within the uterus and cervix during pregnancy and labour either at term or preterm. NO production was compared in the rat uterus and cervix of non-pregnant and pregnant rats on days 18-22 prior to labour, day 22 during delivery, 1 day post-partum and after treatment with either 10 mg onapristone or progesterone. Uterine NO synthesis, reflected in nitrite production, increased during gestation (194.2 +/- 22.6 nmol/g on day 19) compared with the non-pregnant state (76.2 +/- 18.4 nmol/g, P < 0.05) and decreased during term labour and post-partum. Furthermore, injection of lipopolysaccharide (LPS) (100 micrograms/rat i.p.) on day 20 of gestation resulted in a significant increase in NO synthesis after 6 h. Conversely, cervical NO synthesis and nitrite production was low in the non-pregnant (65.1 +/- 9.2 nmol/g) and pregnant animals on days 18-22 of gestation (53.2 +/- 9.0 nmol/g on day 22, P > 0.05), but markedly increased during term labour (139 +/- 28.6 nmol/g, P < 0.05). Treatment with the antiprogestin onapristone suppressed uterine NO production and increased cervical production while continuous administration of progesterone from day 19 had the opposite effect. LPS produced a significant increase in cervical NO production in both the pregnant (8-fold) and non-pregnant (4-fold) states. All three known NOS isoforms (i.e., iNOS, nNOS and eNOS) were detected in the cervical samples but only two were present in the uterus (iNOs and eNOS). An increase in the presence of iNOS occurred during labour at term compared with cervices collected from day 19. This was contrary to the measurements of the isoform in the uterus. Also, there was a similar increase of nNOS in the cervix during labour. This isoform seemed absent in the uterus during gestation. No significant changes occurred in the abundance of eNOS in the cervix during labour at term compared with day 19. During preterm labour after onapristone, iNOS concentrations increased significantly in the cervix. In order to examine whether the NO pathway plays a role in cervical ripening, the effects of the nitric oxide synthesis inhibitor L-nitro-arginine methylester (L-NAME) on the duration of delivery and on cervical extensibility were also investigated. The duration of delivery was significantly prolonged in L-NAME-treated rats compared with the control group (2.4-fold). Moreover, cervical extensibility decreased significantly (1.7-fold) after in-vitro incubation with L-NAME (P < 0.005). We conclude that the NO system may have an active role in the cascade of processes involved in preparing the uterus and cervix for parturition.

Animals↗
PubMed2003

Thrombospondin 2 deficiency in pregnant mice results in premature softening of the uterine cervix.

The gradual disorganization of collagen fibers in the stromal connective tissue of the uterine cervix is characteristic of progressive cervical softening during pregnancy. A lack of thrombospondin (TSP) 2 has been shown to be associated with altered collagen fibril morphology of connective-tissue-rich organs such as skin and tendon. The goal of this study was to determine the role of TSP2 in cervical softening by studying a TSP2-null mouse line. Creep testing showed that, in the nonpregnant animal and on Day 10 of pregnancy, there was no difference between the cervical extensibility of the wild-type and the TSP2-deficient mice. However, by Day 14 of pregnancy, the TSP2-null mice showed 4.5-fold increase in cervical extensibility, and by Day 18, a 6.1-fold increase, when compared with wild-type mice. A further indicator of compromised cervical integrity was that, on Days 14 and 18 of pregnancy, the cervix of TSP2-null mice broke rapidly under standard loading conditions that did not break the cervix of wild-type mice. Western blotting showed that TSP2 was expressed in the cervix of mice on Days 14 and 18 of pregnancy but not on Day 10 or in the nonpregnant animal. As determined by immunohistochemistry, the amount of matrix metalloproteinase 2 (MMP2) in the cervix of TSP2-null mice increased 11-fold on Day 14 of pregnancy and 19-fold on Day 18. Thus, TSP2-null mice provide an animal model to assist in the understanding of the molecular basis of spontaneous, premature softening of the uterine cervix.

Animals↗
PubMed2006

The expression of prostaglandin endoperoxide synthase 2 messenger RNA and the proportion of smooth muscle and collagen in the sheep cervix during the estrous cycle.

The use of transcervical artificial insemination in sheep is limited because of the anatomy of the cervix, which restricts the passage of an inseminating pipette into the uterine lumen. There is a degree of natural cervical relaxation at estrus that enables greater penetration with an inseminating pipette. We hypothesize that this relaxation may be regulated by cervical prostaglandin synthesis and remodeling of the cervical extracellular matrix. The present study investigated the changes in prostaglandin endoperoxide synthase 2 (PTGS2) mRNA expression and the proportion of smooth muscle and collagen in the sheep cervix during the estrous cycle. Sheep cervices were collected at four stages of the estrous cycle: prior to the LH surge, during the LH surge, after the LH surge, and during the luteal phase. The expression of cervical PTGS2 mRNA was determined by in situ hybridization, and the proportion of smooth muscle and collagen in the cervix was investigated by Masson trichrome staining. The expression of PTGS2 mRNA in the sheep cervix was greatest prior to the LH surge, when estradiol concentrations were also greatest. The increase in PTGS2 mRNA expression was associated with an increase in the proportion of collagen in the sheep cervix. We propose that prior to the LH surge, estradiol may stimulate PTGS2 mRNA expression and hence prostaglandin E2 synthesis in the sheep cervix to regulate cervical relaxation, most likely through the rearrangement of collagen bundles within the cervical extracellular matrix.

Animals↗