Non-pregnant Uterus Research Articles

A laparoscopic approach to treating torsion of a nonpregnant uterus accompanied by a large ovarian cyst in a premenarchal girl

A 10-year-old premenarchal girl was admitted to our hospital with moderate abndominal pain, although presenting no vomiting or abdominal rebound tenderness. A large abdominal mass was visible and palpable in the periumbilical and epigastric regions. Results of physical examination revealed that the general health status was satisfactory. Computed tomographic scan revealed a large, thin-walled cyst occupying nearly the entire peritoneal cavity. The other viscera were of normal aspect. A laparoscopic approach revealed a left ovarian cystic tumor that was twisted 360° in conjunction with the uterine corpus with hemorrhagic infarction. A partial hysterectomy and a left salpingo-oophorectomy were carried out. The tumor was classified as mature cystic teratoma of the ovary accompanied by hemorrhagic necrosis, not only of the cyst but also of the left uterine tube and the uterine corpus.

Blockade of adhesion molecule CD146 causes pregnancy failure in mice

Unexplained pregnancy loss and recurrent miscarriage seriously impair human fecundity. However, the underlying molecular mechanisms remain elusive. Recent studies suggest that the adhesion molecule CD146 may be involved in unexplained recurrent miscarriage. Here, we investigate the effect of CD146 on early pregnancy. Using in situ hybridization and immunohistochemistry, we found that CD146 was specifically expressed in the receptive maternal uteri and invasive embryonic trophoblasts during the early stages of pregnancy, but it was completely absent in the non-pregnant uterus. Our in vitro studies demonstrated that blocking CD146 with a function-perturbation antibody AA98 significantly inhibited the attachment of blastocysts onto the receptive uterine luminal epithelial monolayer, the trophoblastic outgrowth of blastocysts and ectoplacental cones, and the secretion of matrix metalloproteinases. Animal experiments showed that applying this antibody before embryo implantation caused pregnancy failure in mice. Our data present direct evidence for the role of CD146 in mediating embryonic attachment and trophoblastic invasion, and provide new insight into the molecular mechanism underlying unexplained pregnancy loss and recurrent miscarriage.

Influence of pregnancy and labor on the occurrence of nerve fibers expressing the capsaicin receptor TRPV1 in human corpus and cervix uteri

BackgroundCervical ripening is a prerequisite for a normal obstetrical outcome. This process, including labor, is a painful event that shares features with inflammatory reactions where peripheral nociceptive pathways are involved. The capsaicin and heat receptor TRPV1 is a key molecule in sensory nerves involved in peripheral nociception, but little is known regarding its role in the pregnant uterus. Therefore, the aim of this study was to investigate human corpus and cervix uteri during pregnancy and labor and non-pregnant controls for the presence of TRPV1.MethodsWe have investigated human uterine corpus and cervix biopsies at term pregnancy and parturition. Biopsies were taken from the upper edge of the hysterotomy during caesarean section at term (n = 8), in labor (n = 8) and from the corresponding area in the non-pregnant uterus after hysterectomy (n = 8). Cervical biopsies were obtained transvaginally from the anterior cervical lip. Serial frozen sections were examined immunohistochemically using specific antibodies to TRPV1 and nerve markers (neurofilaments/peripherin).ResultsIn cervix uteri, TRPV1-immunoreactive fibers were scattered throughout the stroma and around blood vessels, and appeared more frequent in the sub-epithelium. Counts of TRPV1-immunoreactive nerve fibers were not significantly different between the three groups. In contrast, few TRPV1-immunoreactive fibers were found in nerve fascicles in the non-pregnant corpus, and none in the pregnant corpus.ConclusionIn this study, TRPV1 innervation in human uterus during pregnancy and labor is shown for the first time. During pregnancy and labor there was an almost complete disappearance of TRPV1 positive nerve fibers in the corpus. However, cervical innervation remained throughout pregnancy and labor. The difference in TRPV1 innervation between the corpus and the cervix is thus very marked. Our data suggest that TRPV1 may be involved in pain mechanisms associated with cervical ripening and labor. Furthermore, these data support the concept that cervix uteri may be the major site from which labor pain emanates. Our findings also support the possibility of developing alternative approaches to treat labor pain.

Reproductive hormones in plasma over the menstrual cycle in primary dysmenorrhea compared with healthy subjects

The pathogenesis of primary dysmenorrhea is still poorly understood. The objective of the present investigation was to study differences in plasma concentrations of reproductive hormones in women with primary dysmenorrhea vs. healthy controls. In a prospective, parallel-group study we determined the plasma concentrations of oxytocin, vasopressin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17β-estradiol (17β-E2), progesterone and prostaglandin F2α metabolite (15-keto-13,14-dihydro-PGF2α) over one menstrual cycle in eight women with primary dysmenorrhea and eight healthy volunteers. In dysmenorrheic women the plasma concentration of oxytocin was significantly higher at menstruation (p = 0.0084) and that of vasopressin significantly lower at ovulation (p = 0.0281) compared with healthy women. They had also higher FSH levels in the early follicular phase (p = 0.0087) and at menstruation (p = 0.0066) and the 17β-E2 concentration was higher in the late follicular phase (p = 0.0449). No differences were seen for LH, progesterone and PGF2α metabolite. The differences of oxytocin, vasopressin, FSH and 17β-E2 concentrations found in plasma suggest an involvement of these hormones in mechanisms of primary dysmenorrhea. These mechanisms seem to be mainly regulated through the hypothalamus and pituitary. The influence of oxytocin on the non-pregnant uterus seems to be more important than earlier believed.

Decidual Heparanase Activity Is Increased During Pregnancy in the Baboon (Papio anubis) and in In Vitro Decidualization of Human Stromal Cells1

Implantation is a complex process involving interactions between the embryo and the uterus. Adhesion, remodeling of the maternal vasculature, and decidualization are crucial events necessary for successful implantation to occur. Heparanase (HPSE), an endo-beta-D-glucuronidase, cleaves heparan sulfate at specific sites, leading to release of growth factors that may be involved in decidualization and remodeling of the maternal vasculature. HPSE also can function as a cell adhesion molecule. The aim of this study was to determine the expression of HPSE in the uteri of nonpregnant and pregnant baboons as well as in human stromal fibroblasts decidualized in vitro. We examined the localization and expression of HPSE using immunohistochemistry, Western blotting, RT-PCR, and activity assays. In nonpregnant baboon uteri, HPSE expression was localized to the apical surface of the glandular epithelia and in glandular secretions. However, in pregnant baboon uteri, HPSE was localized primarily in decidua. Uteri obtained at midpregnancy had higher heparanase activity compared with the nonpregnant uteri. A slight increase in HPSE expression was observed in human stromal fibroblasts decidualized in vitro. HPSE and HPSE2 mRNA transcripts were present in both decidualized tissue and cells. Increases in heparanase activity in the decidua from pregnant baboon uteri compared with tissue from nonpregnant animals and in human stromal fibroblasts decidualized in vitro suggest that HPSE plays a role in extracellular matrix remodeling and in increasing heparin-binding growth factor release during embryo implantation.

Effect of chloroquine on strips of non-pregnant and pregnant mice uteri in-vitro

Chloroquine (CQ) remains the household drug for the treatment of malaria especially among pregnant women. However, there are reports that CQ inhibits the contractile process in non-pregnant rat's uterus. The aim of this study is to compare responses to CQ between non-pregnant and pregnant mice and identify some mechanisms involved. Experiments were carried out in non-pregnant and pregnant mice pretreated 24 hours before with 1.5 mg/kg-body weight stilboesterol given orally. Strips of uterine smooth muscle, approximately 5 mm in diameter, were mounted in a 20 ml organ bath containing De Jalon solution bubbled with a 95% O2-5% CO2 gas mixture. Responses of the strips to graded concentration of acetylcholine (ACh) (10(-9) to 10(-5) mol/L), oxytocin (OXY) (10(-5) to 10(-2) IU/ml) and CQ (10(-6) to 4 x 10(-4) mol/L) were investigated. The strips were then incubated in 4 x 10(-4) mol/L CQ for 15 mins and the cumulative dose responses for OXY were repeated. To investigate mechanism of action, the strips were incubated for 15 mins in N(w)-nitro L-arginine methyl ester (L-NAME) and the cumulative responses to CQ repeated. Each investigation was carried out in fresh tissue mounted on Grass Model FT03 force transducer coupled unto a 4-channel Grass Model 7D Polygraph. CQ (low to moderate level), ACh and OXY led to increases in contractile responses in the uteri. There were greater contractile responses in non-pregnant than pregnant mice to CQ and ACh. At high doses, CQ had an inhibitory effect on the uterine contraction. Incubating in CQ led to abolition of contractile responses to OXY and ACh. In the presence of L-NAME, inhibitory effect of CQ at high doses was attenuated in pregnant mice only. The results suggest that CQ at high doses inhibits contractile responses in non-pregnant and pregnant mice. Enhanced nitric oxide bioactivity attenuated this inhibitory effect.

The effects of α‐methyldopa on myometrial noradrenaline release and myometrial contractility in rat

alpha-Methyldopa is a classic antihypertensive agent, used routinely in the treatment of pregnancy-induced hypertension. However, only a few data are available about its direct uterotropic effect. Accordingly, the aim of the present study was to investigate the direct effects of alpha-methyldopa on the myometrial adrenergic functions in rat. The effects of alpha-methyldopa on the sympathetic transmission in the non-pregnant, early pregnant and late-pregnant myometrium were investigated by a superfusion technique. Myometrial samples from control and alpha-methyldopa-treated (200 mg/kg i.p. for 7 days) non-pregnant, 7-day and 21-day pregnant rats were saturated with [(3)H]noradrenaline, and the liberation evoked by electric field stimulation was determined. The contractility responses to alpha- and beta-adrenergic stimulation were additionally characterised by generating concentration-response curves of myometrial rings to noradrenaline and terbutaline in the same arrangement. The changes in the density and affinity of the adrenergic receptors (alpha(2) and beta(2)) were investigated by a radioligand binding technique. The treatment with alpha-methyldopa substantially decreased both the [(3)H]noradrenaline uptake and release in both the non-pregnant and early pregnant uterus, while treatment-dependent changes were observed at term only in the uptake capacity. The contractility response to exogenous alpha-sympathomimetics was higher in the group treated in early pregnancy, and a decreased terbutaline-induced relaxation was observed in the non-pregnant state and at term. The treatment resulted in increased affinity for alpha(2) receptors in early pregnancy, while K(d) for beta(2) was increased at term. Our experimental data suggest that besides its antihypertensive effect, alpha-methyldopa may influence the adrenergic transmission of the pregnant uterus. Our results indicate that the agent decreases the efficacy of beta(2)-adrenergic agonists at term pregnancy and increases the response to alpha-sympathomimetics in early pregnancy.

The Effect of Potassium Channel Opener Pinacidil on the Non‐Pregnant Rat Uterus

The effects of the K(+) channel opener, pinacidil on the spontaneous rhythmic contractions and contractions provoked by electrical field stimulation (50 Hz) or by oxytocin were investigated in the isolated uterus of the non-pregnant rat in oestrus. Pinacidil produced more potent inhibition of oxytocin-elicited contractions than of spontaneous rhythmic contractions or electrical field stimulation-induced contractions. Glibenclamide, a selective blocker of adenosine triphosphate (ATP)-sensitive K(+) (K(ATP)) channels, antagonized the pinacidil-induced inhibition of contractions elicited by oxytocin in a competitive manner. However, the pinacidil-induced inhibition of electrical field stimulation-elicited contractions and spontaneous rhythmic contractions was antagonized non-competitively by glibenclamide. In the uterine strips pre-contracted with 80 mM K(+), the pinacidil-induced maximal relaxation was not affected. The present data show that pinacidil exhibits potent relaxant properties in the rat non-pregnant uterus in oestrus and therefore should be taken into account as a possible agent for treatment of dysmenorrhoea. Based on glibenclamide affinity, it appears that the inhibitory response to pinacidil involves K(ATP )channels. We need further investigations to explain why the interaction between glibenclamide and pinacidil in this experimental model depends on the nature of contractions. The ability of pinacidil to completely relax the rat non-pregnant uterus pre-contracted with K(+)-rich solution suggests that K(+) channel-independent mechanism(s) also play a part in its relaxant effect.

Different roles of α 2-adrenoceptor subtypes in non-pregnant and late-pregnant uterine contractility in vitro in the rat

The roles of the α 2-adrenoceptor (α 2-AR) subtypes (α 2A-, α 2B- and α 2C-AR) in uterine contractility have not been investigated. The aims of this study were to identify these receptors in the non-pregnant and the late-pregnant rat myometrium and to determine their roles in contractions. We found that the myometrial α 2-AR subtypes are involved differently in the control of late-pregnant contractions, while they have no influence on the contractions of the non-pregnant myometrium. The myometrial expressions of the α 2-AR subtypes were determined by RT-PCR and Western blotting techniques. In vitro contractions were stimulated with noradrenaline, and its effect was modified with the selective antagonists BRL 44408 (α 2A), ARC 239 (α 2B/C) and spiroxatrine (α 2C). cAMP production was followed by noradrenaline stimulation in the presence of isobutylmethylxanthine and forskolin, and alterations induced in it by the antagonists were determined with an Enzyme Immunoassay Kit. The most effective antagonist was tested on labour-induced uteri in vitro. All the α 2-AR subtypes were identified in both non-pregnant and pregnant uteri. Noradrenaline was not able to contract the non-pregnant tissue in the presence of propranolol and doxazosin, while its contracting effect in the pregnant uteri was enhanced by BRL 44408, spiroxatrine and the combination BRL 44408 + spiroxatrine. ARC 239 exerted a strong inhibitory effect on noradrenaline-stimulated contractions. The increasing and the decreasing effects of the compounds were confirmed by the changes in the intracellular cAMP levels. The effect of ARC 239 on the labour-induced myometrium was similar to that on the 22-day-pregnant myometrium. The stimulation of α 2-ARs does not evoke contractions in the non-pregnant uterus. The α 2A- and α 2C-ARs mediate decreases, while the α 2B-AR mediates an increase in the contractions in the 22-day-pregnant myometrium. These differences may offer new targets for drugs against premature contractions in pregnancy.

LOCALIZATION AND QUANTIFICATION OF CELLULAR PRION PROTEIN (PrPC) EXPRESSION IN THE NONPREGNANT UTERUS, AND IN EMBRYOS AND PLACENTAL TISSUES FROM EARLY PREGNANCY IN SHEEP

Scrapie, a prion disease of sheep, is thought to be transmitted at birth via the placenta. A misfolded form of the prion protein, termed PrPSc, is credited with causing scrapie. However, the functions of the normal (cellular) prion protein (PrPC), how it becomes misfolded, and its possible roles in placental biology and fetal development are still unknown. Our hypothesis was that PrPC would be expressed in a cell-specific manner in embryos, in the non-pregnant (NP) uterus, and at the fetal and maternal interface of the placenta. To localize the expression of the PrPC protein in developing embryos, uterine tissues, and maternal placenta (caruncular, CAR) and fetal placenta (cotyledonary, COT), and to quantify expression of PrPC mRNA in CAR and COT, tissues were collected from ewes (n = 5/group) on day 10 of the estrous cycle (NP control) and on days 20, 22, 24, 26, 28, or 30 of early pregnancy. Embryos were fixed in formalin, and the PrPC protein was detected by immunohistochemistry (IHC). NP uterine tissues and placental CAR and COT were also fixed in formalin for IHC or snap-frozen for qRT-PCR. In embryos, PrPC protein was predominantly present in the mesonephros on days 20 through 26 of pregnancy but was also found in the spinal cord and midbrain. By day 26, PrPC protein was also found in the fetal liver. By days 28 through 30, PrPC protein was expressed in fetal mesonephros, ectoderm, and in areas surrounding the spinal cord and the intestinal tract. In the NP uterus, PrPC was present at the apical borders of the luminal epithelium and the epithelium of a few luminal glands. PrPC was also expressed in the outer smooth muscle layer of larger arterioles of NP and pregnant uterus and in scattered stromal cells of the deep intercaruncular areas of the NP uterus. In CAR, PrPC protein was found in the cytoplasm of the flattened luminal epithelial cells apposed to the fetal membranes, whereas in COT, PrPC protein was localized to mononucleate, binucleate, and syncytial trophoblast cells. PrPC mRNA expression was similar in CAR and NP uterine tissues. However, in COT, PrPC mRNA expression increased (P < 0.01) from days 20 to 28 of early pregnancy and then decreased (P < 0.01) on day 30 of pregnancy to the levels present on day 24. The pattern of PrPC mRNA expression in COT was best described by a sigmoidal exponential regression (P < 0.001; R2 = 0.7007). Localization of PrPC to specific cells and structures within embryos, and in uterine and placental tissues suggests that PrPC has a significant, but unknown, role during the estrous cycle and during developmental processes of early pregnancy. Thus, further investigation is needed to determine the normal function of PrPC in the female reproductive process, placental growth, and fetal development. Supported by Hatch Project ND1727; USDA, ARS, ADRU 5348-32000-021-00D; NIH grant RO1 HL64141; and NIH grant P20 RR016741 from the INBRE program of the NCRR. (platform)

A comparison of uterine peristalsis in women with normal uteri and uterine leiomyoma by cine magnetic resonance imaging

Objective The non-pregnant uterus shows wave-like activity (uterine peristalsis). This pilot study was intended to determine: (1) whether uterine peristalsis during the menstrual cycle is detectable by cine magnetic resonance imaging (MRI); (2) the effects of leiomyoma on uterine peristalsis. Study design Mid-sagittal MRI was performed sequentially with T2-weighted single-shot fast spin-echo (SSFSE) in 3 normal ovulatory volunteers and 19 premenopausal women with uterine leiomyoma. Direction and frequency of movement of the junctional zone were evaluated using a cine mode display. Results Junctional zone movement was identified in all subjects. Direction of uterine peristalsis in normal volunteers was fundus-to-cervix during menstruation, cervix-to-fundus during the periovulatory phase, and isthmical during the mid- and late-luteal phases. Abnormal peristaltic patterns were detected in three of five patients with uterine leiomyoma during menstruation and in the mid-luteal phase of the cycle, respectively. Conclusion Cine MRI is a novel method for evaluation of uterine peristalsis. Results of this pilot study suggest that abnormal uterine peristalsis during menstruation and the mid-luteal phase might be one of the causes of hypermenorrhea and infertility associated with uterine leiomyoma.

Nicotine Potentiates the Electrical Field Stimulation-Evoked Contraction of Non-Pregnant Rabbit Myometrium

The women who smoke have lower fertility rates which might be due to harmful effects of nicotine on tubal function and menstrual cycle. Although the uterine contractility of the non-pregnant uterus plays an important role in the human reproduction process, the influence of nicotine on the contractile responses in uterus is not known. Nicotine increases the release of neurotransmitters following nerve stimulation both in the central and peripheral nervous system through acting on nicotinic acetylcholine receptors (nAchRs). The aim of this study was to examine whether the electrical field stimulation (EFS)-evoked contraction is altered in rabbit myometrium strips in the presence of nicotine to evaluate the changes in contractility. EFS-evoked contractile responses were recorded from myometrium strips obtained from non-pregnant rabbits in the absence and presence of nicotine. Nicotine led to the increase in the amplitudes of the EFS-evoked contractile responses in a dose-dependent manner. Therefore, the effects of hexamethonium, cadmium, indomethacin, atropine, and N(omega)-Nitro-L-arginine methyl ester hydrochloride were tested on the EFS-evoked contractions in the absence or presence of nicotine to clarify the mechanisms of nicotine-induced potentiation in EFS-evoked contractile responses. Indomethacin, a non-selective cyclooxygenase inhibitor, and hexamethonium, a ganglionic blocker, inhibited nicotine-induced increase in EFS-evoked responses, whereas other chemicals produced no effect. These results suggest that nicotine-induced potentiation may be mediated by nAchRs and prostaglandins. In conclusion, failure of quiescence in the uterus due to increased contractility by nicotine might be one of the factors contributing to infertility in female smokers.

Oxytocin – a stimulator of directed sperm transport in humans

Rhythmic peristaltic contractions of the muscular wall of the non-pregnant uterus, as well as rapid sperm transport from the vagina to the Fallopian tubes, have long been documented by means of vaginal sonography and hysterosalpingoscintigraphy. Uterine peristaltic activity reaches a maximum before ovulation and is controlled via oestradiol secretion from the dominant follicle systemically and into the utero-ovarian countercurrent system; it is also enhanced by oxytocin. In this study, the effect of oxytocin and its receptor antagonist atosiban on uterine peristalsis and thus directed sperm transport during the mid and late follicular phases was examined. Atosiban did not show any effect either on frequency or on pattern of the peristaltic contractions. However, oxytocin significantly increased the rapid and directed transport of radiolabelled particles representing spermatozoa from the vagina into the Fallopian tube ipsilateral to the site of the dominant follicle ( P = 0.02, 0.04 and 0.02 after 1, 16 and 32 min of documentation respectively). It seems reasonable to assume that oxytocin plays an important, although not critical, role in the mechanisms governing rapid sperm ascension that, at least in humans, were developed to rapidly preserve an aliquot of spermatozoa following intercourse.

Presence of sensory nerve corpuscles in the human corpus and cervix uteri during pregnancy and labor as revealed by immunohistochemistry

BackgroundThe uterus is exposed to changes such as enlargement and distension during pregnancy and labor. In these processes and in the process of cervical ripening, proprioceptive information is likely to be of great importance. Therefore, we wanted to study the possible existence of sensory nerve corpuscles in uterine corpus and cervix during pregnancy and labor. Studies on this aspect have not previously been perfomed.MethodsBiopsies were taken from the upper edge of the hysterotomy during caesarean section at term (n = 8), in labor (n = 5) and from the corresponding area in the non-pregnant uterus after hysterectomy (n = 7). Cervical biopsies were obtained transvaginally from the anterior cervical lip. Serial cryostat sections were prepared for immunohistochemistry using polyclonal antibodies against nerve growth factor receptor p75, protein gene product 9.5 and S-100.ResultsStructures with the characteristics of sensory nerve corpuscles were observed in several specimens after staining for p75, PGP 9.5 and S-100. They were observed in specimens of the non-pregnant corpus and cervix and also in specimens of the pregnant cervix before onset of labor. However, they were absent in all specimens during labor.ConclusionSensory corpuscles have here for the first time been detected in the human corpus and cervix uteri. Studies on the importance of the corpuscles in relation to the protective reflex actions that occur in the uterus during pregnancy should be performed in the future.

Interstitial Cajal-like cells (ICLC) as steroid hormone sensors in human myometrium: immunocytochemical approach.

Expression of estrogen (ER) and progesterone (PR) receptors was investigated in cultured human normal myometrial cells (non-pregnant uterus, fertile period). The ER and PR expression was studied by immunohistochemistry and immunofluorescence on either myocytes or interstitial Cajal-like cells (ICLC). Only those cells double immunostained for c-kit and steroid receptors were considered as ICLC. ER and/or PR immunoreactivity was localized in ICLC, primarily concentrated at the nucleus level, but it was also observed in the cell body (cytoplasm) and processes. Stronger immunopositive reaction in the ICLC nucleus for PR than for ER was noted. Under our experimental conditions, a clear positive repeatable reaction for steroid receptors could not be detected in myocytes. In conclusion, these data suggest that ICLC could be true hormonal ‘sensors’, possibly participating in the regulation of human myometrial contractions (via gap junctions with myocytes and/or by paracrine signaling).

Uterine contractility in response to different prostaglandins: results from extracorporeally perfused non-pregnant swine uteri

Prostaglandins (PGs) are important stimulators of uterine contractility. Limited data are available at present on the effects of different PGs on uterine contractility, measured using intraluminal pressure changes in the complete uterus. The goal of this study was to assess dynamic changes in uterine contractility and peristalsis in response to PGs in comparison with the effects of oxytocin administration. An extracorporeal perfusion model of swine uteri was used, which keeps the uterus in a functional condition, and is appropriate for the study of physiological questions. Oxytocin- and PG-induced uterine contractility and peristalsis were assessed using an intrauterine double-chip microcatheter. A dose-dependent increase in intrauterine pressure (IUP) in the isthmus uteri (P < 0.001) and the corpus uteri (P < 0.001) was observed after the administration of PGF(2alpha) and oxytocin, which reached a plateau after further stimulation. A dose-dependent increase in IUP in the isthmus uteri (P < 0.001) and the corpus uteri (P < 0.001) was also observed after the administration of PGE(1) and PGE(2), with a plateau in IUP in the middle-concentration range and a decrease in the course of further stimulation. PGE(2) caused significantly more contractions starting in the corpus uteri and moving to the isthmus uteri (P = 0.008). The direction of most contractions caused by PGE(1), PGE(2) and oxytocin differed from that of PGF(2alpha). This study demonstrates that the PGs tested modulate contractility in non-pregnant swine uteri in a characteristic way, resulting in different contractility patterns.

Role of estrogen and progesterone in the regulation of uterine peristalsis: results from perfused non-pregnant swine uteri

Adequate uterine contractility and peristalsis are involved in the transport of semen and gametes and in successful embryo implantation. Estrogen and progesterone fluctuate characteristically during the menstrual cycle. It has been suggested that both hormones influence uterine peristalsis in characteristic ways. An extracorporeal perfusion model of the swine uterus was used that keeps the uterus in a functional condition and is suitable for the study of physiological questions. The effects of estrogen and progesterone on oxytocin-induced uterine peristalsis were assessed using an intrauterine double-chip microcatheter. Estrogen perfusion was associated with an increase in intrauterine pressure (IUP) in a dose-dependent manner. There was a significant difference between the IUP increase measured in the isthmus uteri and that in the corpus uteri, resulting in a cervico-fundal pressure gradient. Estrogen perfusion resulted in a significantly higher rate of peristaltic waves starting in the isthmus uteri and directed towards the corpus uteri. Progesterone was able to antagonize the estrogen effect in general. This study demonstrates that estrogen and progesterone have differential effects in the regulation of uterine peristalsis. The present observation shows that estrogen stimulates uterine peristalsis and is able to generate a cervico-fundal direction of peristalsis, whereas progesterone inhibits directed uterine peristalsis.

Perfused Non-Pregnant Swine Uteri: A Model for Evaluating Transport Mechanisms to the Side Bearing the Dominant Follicle in Humans

Adequate uterine contractility and periovulatory peristalsis, interpreted as "rapid sperm transport" to the side bearing the dominant follicle, may be a precondition for successful reproduction in humans. Estrogen and progesterone fluctuate characteristically during the menstrual cycle, and their source is the dominant follicle and corpus luteum. The question is, how is the direction to the left or right side of transport mechanisms influenced? An extracorporeal perfusion model of the swine uterus was used that maintained the uterus in a functional condition and that was suitable for the study of physiological questions. The effects of side-dependent estrogen, progesterone, and estrogen plus progesterone perfusion on oxytocin-induced uterine peristalsis were assessed using two intrauterine microcatheters placed in each horn of the swine uterus. Estrogen perfusion was associated with an increase in intrauterine pressure (IUP) in a dose-dependent manner only in the estrogen-perfused horn of the swine uterus. There was a significant difference between the IUP increase measured in the estrogen-perfused horn and that in the non estrogen-perfused horn of the swine uterus. Progesterone perfusion showed no effect in general. Furthermore, progesterone antagonized the estrogen effects. This study demonstrates that side-dependent estrogen perfusion resulted in side-dependent contractility in the swine uterus perfusion system used. These observations show that estrogen stimulates uterine contractility in the estrogen-perfused uterine horn and that estrogens may be the "trigger" for the transport mechanisms to the side bearing the dominant follicle during the periovulatory phase through their locally increased concentration and distribution via the utero-ovarian counter-current system in humans.

Control and function of uterine peristalsis during the human luteal phase

Rhythmic peristaltic contractions of the muscular wall of the non-pregnant uterus can be demonstrated throughout the menstrual cycle, with a maximum just before ovulation. However, not only during the follicular phase but also during the luteal phase, the uterus shows remarkable contractile activity. The present study was conducted in order to examine uterine peristaltic activity and its function during the luteal phases of the human menstrual cycle. The results of vaginal sonography of uterine peristalsis, of hysterosalpingoscintigraphy and of the documentation of the sites of embryo implantation in natural and artificial cycles have shown that uterine peristalsis during the luteal phase is controlled by systemic and probably even more by local hormonal secretion from the fresh corpus luteum, and facilitates the fundal implantation of the blastocyst predominantly ipsilateral to the site of the dominant ovarian structure. Furthermore, this study suggests that the defence against the infiltration and inflammation of the upper genital tract, and thus the degradation of the implanted embryo, represents a further and phylogenetically old and genuine function of the archimetra, which in placentalia was modified in order to participate in the control of invasion of the endometrium by the trophoblast.

Structural and functional comparison of mast cells in the pregnant versus nonpregnant human uterus

To characterize uterine mast cells and investigate uterine muscle strips contractile responses to challenge with an allergen in nonpregnant and pregnant women. A double-antibody labeling technique was used to identify tryptase positive or chymase-tryptase-positive mast cells in uterine samples from term pregnant and nonpregnant women. Longitudinal myometrial strips were prepared from biopsies of hysterectomy specimens from patients undergoing procedures for benign indications and women who had elective cesarean sections. Responses to ragweed antigen were compared in uterine tissues from allergic and nonallergic patients and with passively sensitized tissues in the absence or presence of H1 receptor antagonist and a cyclooxygenase inhibitor. Tryptase-chymase-positive mast cells were predominant in nonpregnant myometrium, whereas tryptase-positive cells were dominant in pregnant myometrium. Mast cell density was significantly higher in tissue from pregnant women than those of nonpregnant women. Studies in tissues from patients with known allergy to ragweed, as well as in passively sensitized tissues, showed an immediate and substantial increase in the frequency and force of myometrial contraction after a challenge with ragweed antigen. A similar response was observed to histamine. There was no contractile response to antigen challenge in tissues from nonallergic patients. An H1 receptor antagonist partially inhibited the response to antigen, whereas a cyclooxygenase inhibitor had no effect. Sensitized isolated pregnant and nonpregnant human uterine tissue is capable of responding to antigen challenge with strong myometrial contractions. This ability, along with the increased density of mast cells in pregnant tissues as compared with nonpregnant tissues, indicates a possible role for mast cells in mediating uterine contractility in pregnancy.