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Demonstration that progesterone 'blocks' uterine activity in the ewe in vivo by a direct action on the myometrium.

Intrauterine pressure was monitored in vivo in oestrogen-treated ovariectomized ewes before, during and after treatment with progesterone (50 mg s.c./day for 3 days). Progesterone reversibly reduced the frequency and amplitude of myometrial activity and abolished uterine reactivity to oxytocin (i.v.) and PGF-2alpha (intrauterine infusion). The rate of rise of intrauterine pressure during active pressure cycles was significantly reduced. These results confirm that the action of progesterone on the ovine myometrium is comparable to the classic progesterone 'block'. The intrauterine infusion of PGF-2alpha (10 microgram/min), which elicited a marked mechanical response in the control animals, failed to stimulate the progesterone-'blocked' uterus, suggesting that the inhibition produced by progesterone is due to a direct action of the hormone on the uterine muscle and not to an indirect mechanism operating through endometrial prostaglandin output.

Animals

Transcriptomics and proteomics reveal associations between myometrium and intrauterine adhesions.

BACKGROUND: Intrauterine adhesions (IUAs) is a gynecological condition with a poor therapeutic prognosis, that severely threatens the fertility and the reproductive physiology and psychological health of women. Our previous research on the use of umbilical cord mesenchymal stem cells (HUCMSCs) for treating IUAs revealed that CM-Dil-labelled HUCMSCs were barely distributed in the endometrial epithelium. Instead, these cells were predominantly found in the myometrium, with no statistically significant difference in distribution compared to the endometrial stromal cells. Therefore, we aimed to explore the associations between the myometrium and IUAs. METHODS: Eight patients with moderate and 5 severe lesional IUAs were included in the experimental group. The control group included 7 patients whose inner and outer myometrium were normal. We used H&E, Masson's trichrome and immunohistochemical staining to obtain the pathological features of the tissues. Transcriptomic and proteomic analyses were conducted to identify differentially expressed genes, proteins and enrichment pathways. RESULTS: Both IUAs lesion tissues expressed the smooth muscle markers &#x3b1;-SMA and H-caldesmon, and there was no significant difference between severe IUAs tissue and normal myometrium (p&#x2009;>&#x2009;0.05). Transcriptomic and proteomic data revealed that genes and proteins involved in cell mitosis, such as KIF14, KIF4A, and CIT, were downregulated in both IUAs lesion tissues compared with the inner myometrium (p&#x2009;<&#x2009;0.05). Additionally, some genes or proteins that participate in activating the complement-coagulation cascade system and extracellular matrix (ECM) degradation also significantly differed (p&#x2009;<&#x2009;0.05). CONCLUSIONS: Transcriptomic and proteomic data revealed a correlation between endometrial injury and the myometrium. These findings preliminarily revealed that the myometrium possibly contributes to the aetiology and progression of IUAs through dual mechanisms. On the one hand, the myometrium inhibits endometrial regeneration by suppressing the cell mitogenic pathway. On the other hand, it promotes fibrosis by activating the complement-coagulation cascade system and inhibiting the ECM degradation pathway. These new findings increase our understanding of the pathogenesis of IUAs and potentially contribute to the application of precision clinical treatment for IUAs.

Humans

The effect of an intrauterine device on myometrial glycogen in the hamster.

The myometrical glycogen content of the uterine horns of cycling, castrated and castrated hormone-treated hamsters was basically unaffected by the presence of an intrauterine device (IUD). The study also indicates that visual evaluation of histochemical localization of glycogen is not adequate to determine minor differences in staining intensity. The "estrogen-like" effect or stimulatory effect of the IUD on uterine glycogen in the rat is not duplicated in the hamster.

Animals

Effects of oral and intrauterine administration of contraceptives on the uterus.

Combined regimen contraceptive steroids produce precocious endometrial secretion, followed by involution leading to a suppressed endometrium with small tubular glands and failure of spiral arterioles to develop; decidua-like stromal changes are dose related as is dilatation of venules. Thrombosis of the latter, perhaps estrogen mediated, leads to local tissue infarction and is the proximate cause of "breakthrough bleeding". Sequential regimen contraceptive steroids lead to retarded endometrial secretion, failure of spiral arterioles to develop, and a weak decidua-like stromal transformation. Contraceptive steroids occasionally produce polypoid lesions of the endocervix with atypical microglandular hyperplasia. There are conflicting reports about the effects of contraceptive steroids on the squamous epithelium of the exocervix, but they neither protect against cancer nor cause it in the usually accepted sense. Uterine leiomyomas may exhibit increased cellularity and bizarre, hyperchromatic nuclei or mutinucleation in women receiving contraceptive steroids. Both polyethylene and metal-containing intrauterine devices may initiate inflammatory responses in the endometrium varying from mild to severe, related to the time the device has been in contact with the mucosa. Salpingitis and ectopic pregnancy are increased in frequency in device users.

Adult

Heparin-like activity in uterine fluid.

Uterine fluid was collected from a group of normal patients and a group of patients with menorrhagia. Heparin-like activity was detected in 34 out of 38 samples using an anti-Xa heparin assay. The heparin-like activity in uterine fluid was inhibited by adding the heparin antagonist hexadimethrine bromide to the assay. Concentrations of fibrinogen-fibrin degradation products (FDPs) were measured in five samples of uterine fluid. FDPs in the concentration detected had no effect on the anti-Xa assay. Heparin-like activity was higher in the group with menorrhagia, although the differences were not significant. Heparin-like activity increased throughout the menstrual cycle and decreased during menstruation, suggesting a possible cyclical variation in activity. There was no correlation between mast cell numbers in the endometrium and myometrium and heparin-like activity in uterine fluid and no correlation between the numbers and the stage in the menstrual cycle. In a few patients with intrauterine contraceptive devices (IUCDs) heparin-like activity was increased.

Body Fluids

Prostaglandins and the initiation of labor.

A total of 96, dated pregnant, New Zealand white rabbits were studied. In 58 animals the intrauterine pressure (IUP) of the unstimulated and PGF2alpha-stimulated myometrium was recorded, by the extraovular microballoon technique, before, during and after parturition. In the remaining 38 the concentrations of PGE and PGF and progesterone (P) were measured by radioimmunoassays (RIA). The samples were collected individually or sequentially during the perinatal period from uterine tissue and uterine or peripheral vein blood. At the critical time, at around parturition, when the myometrium is converted from a suppressed and refractory muscle into a spontaneously active and reactive organ (quantitated by recording the IUP), the uterine PGE and PGF levels decreased rather than increased (quantitated by RIA). Thus, this critical regulatory and functional change of the myometrium cannot be accounted for by an increase in the intrinsic uterine stimulant: PG, but only by a decrease in the suppressor: P. These findings, 46 years after the discovery of P, demand the further exploration of Corner's legacy.

Animals

[The induction of labor by prostaglandin F2alpha Clinical, tocographic and electrohysterographic study].

Induction of labor was performed in 65 patients by intravenous infusion of PgF2alpha. 55 patients were near term and induction made electively. 5 cases failed. No correlation was found between the stade of the cervix and the probability of success nor the length of the induction time. PgF2alpha induced labor needs to be closely monitored (electronical pumps and monitoring) because of the risk of hypertonus. With such a technique the side effects are minimal and no undesirable consequences were observed concerning either the mother or the child. During the course of this investigation a study was performed for the first time of the electrical activity of the human myometrium subjected to PgF2alpha stimulation. (26 recordings through the extra-amniotic intrauterine technique). The pattern of this activity is quite similar to spontaneously occuring alectrical activity.

Apgar Score

Ultrasonic demonstration of myometrial contractions in intrauterine pregnancy.

An incidental finding associated with ultrasound examination of early intrauterine pregnancy is transient thickening of a limited region of the myometrium, which we interpret as a localized contraction. Contractions were demonstrated in nearly all 881 patients examined and were shown to significantly change in configuration within a 30 min period. In all except one patient, the contractions were completely asymptomatic, and they seem to be of no discernible clinical significance.

Adolescent

Menorrhagia, diffuse myometrial hypertrophy and the intrauterine contraceptive device: a report of fourteen cases.

Fourteen uteri, removed for IUD-associated menorrhagia, were studied. Twelve of these IUD-bearing uteri showed pure diffuse myometrial hypertrophy; the other two uteri were enlarged as a result of multiple leiomyomas in one case and extensive deep adenomyosis in the other. The incidence of pure myometrial hypertrophy in the IUD group was far in excess of that observed in a control non-IUD-bearing menorrhagia series, where leiomyomas and/or deep adenomyosis were mostly responsible for the uterine enlargement.

Adult

Comparison of intrauterine prostaglandin metabolism during pregnancy in man, sheep and guinea pig.

Metabolism of prostaglandin F2 alpha (PGF2 alpha) was studied in uterine tissues from pregnant women (n = 10), sheep (n = 6) and guinea pigs (n = 6). Two maternal tissues, myometrium and decidua or maternal placenta, and two fetal tissues, fetal placenta and membranes, were studied in each species. PGF2 alpha was metabolized via the well-known pathway into 15-keto-PGF2 alpha and 13,14-dihydro-15-keto-PGF2 alpha, while 13,14-dihydro-PGF2 alpha was tentatively identified in some tissues. The presence of 15-hydroxyprostaglandin dehydrogenase (PGDH) and 13,14-prostaglandin reductase was demonstrated in all tissues from each of the three species studied, but the quantitative intrauterine distribution of these enzymes differed from one species to another. In man, PGDH activities were highest in fetal membranes followed by fetal placenta and then by decidua and myometrium. In sheep, PGDH activities were highest in the maternal placenta followed in decreasing order by myometrium, fetal placenta and membranes. In the guinea pig, PGDH activity was highest in the fetal membranes followed in decreasing order by maternal placenta, fetal placenta and myometrium. Quantitative assay of PGDH showed that PGDH activity in the pregnant uterus is higher in women than in sheep and guinea pig. The results are discussed in relation to the involvement of prostaglandins in parturition.

Animals

Some clinical and theoretical aspects on prostaglandins in obstetrics and gynecology.

The present article discusses two aspects on prostaglandins, both related to the control of uterine contractility. One concerns a clinical problem, induction of abortion, and argues in favor of systemic instead of intrauterine administration of prostaglandins and the choice of E instead of F analogues. The other relates to the stimulatory effect on the myometrium of some recently detected endogenous prostaglandins. The discussion regarding the endogenous control of myometrial contractility has so far exclusively been focused upon the classical prostaglandins. It is, however, felt that substances like PGH2, PGI2 and thromboxane A2 may play a significant role in the regulation of uterine activity.

Abortion, Induced

Effect of fenoterol and isoxsuprine on myometrial and intervillous blood flow during late pregnancy.

The use of beta-adrenergic agonists in high-risk pregnancies has shown evidence of favorable effects on the fetus. Intravenous injections of 133Xe were given to evaluate the effects of short-term administration of fenoterol (3 microgram/min) and isoxsuprine (150 migrogram/min) on the intervillous and myometrial blood flow in a series of 48 women during the last trimester of pregnancy. Both fenoterol and isoxsuprine treatment increased the maternal heart rate significantly. There was a significant rise in myometrial blood flow when fenoterol was given, but the intervillous blood flow did not change significantly during the administration of either isoxsuprine or fenoterol. Previous oral isoxsuprine treatment did not diminish the cardiac effect of intravenous fenoterol, but the improvement in myometrial blood flow was eliminated. This result indicates that beta-adrenergic agonists may have a specific dilatational effect on the myometrial blood vessels. From the hemodynamic point of view, the beta-adrenergic agonists have a limited value in the treatment of chronic fetal asphyxia or intrauterine fetal growth retardation.

Ethanolamines

Some effects of an intrauterine device on glucosaminoglycans of the hamster uterus.

The effect of an intrauterine device (IUD) on non-heparin sulfomucopolysaccharide (SMP) was studied in castrated, hormone-treated, and cycling hamsters by photographic densitometry of tissue sections stained specifically for SMP with Alcian blue. Non-heparin SMP increased slightly in the myometrium of IUD-containing uteri of all castrated groups, with the increase being significant in only the peanut oil-treated group. The endometrium also showed slight increases in sulfomucin in IUD-containing uteri of peanut oil, progesterone, and estrogen plus progesterone-treated animals. These increases, however, were not statistically significant. In cycling hamsters the IUD had little effect on uterine non-heparin SMP in most cycle stages.

Animals

Myotonia dystrophica: obstetric complications.

We describe the course and outcome of 23 pregnancies in six women affected by myotonia dystrophica in a large Labrador family. A seventh patient had 14 pregnancies, so that the infertility commonly described in this disorder did not apply to this family. The rate of complications was high, particularly in respect of polyhydramnios, premature onset of labor, cesarean section, postpartum hemorrhage, and neonatal deaths. Polyhydramnios indicated that the fetus was abnormal. Direct observation of an atonic uterus at cesarean section supported other evidence that uterine muscle may be affected. We also report a newborn infant with the congenital form of myotonic dystrophy, a manifestation which has been attributed to the effect of a maternal intrauterine factor upon a fetus carrying the gene.

Female

[Investigations of the human isolated nonpregnant uterus contractility in the course of the menstrual cycle by measuring intramyometrial pressure (author's transl)].

In this work, the behaviour of the intramyometrial pressure, registered in the wall of the myometrium of the human isolated nonpregnant uterus, has been followed up. Intramyometrial pressure measurements were performed in 33 uteri. Simultaneously the intravascular pressure was monitored. The values of the intramyometrial pressure correspond with the intrauterine pressure, and the pressure in the uterine cavity, measured with the use of inserted balloon, was a resultant of the intrauterine pressure measured in the corpus uteri and isthmus at the same time. It has been found that in the course of the sexual cycle, nonpregnant human uterus shows irregular contractile activity. The contractile activity of the nonpregnant human uterus is characterized by the lack of coordination of contractions among particular uterine regions registered simultaneously. During the course of the menstrual cycle the isthmus region was dominating and revealed a pacemaker properties and during menstrual bleeding corpus uteri dominated. The results were discussed and the close relationship between uterine contractility and intravascular pressure was underlined.

Female

The effects of ovariectomy and stretch on the regulatory profile and activity of the uterus.

Following ovariectomy of five New Zealand white rabbits at day 25 of pregnancy, the intrauterine pressure (IUP) and uterine progesterone (P) and prostaglandin (PG) levels were measured sequentially at days 25, 26 and 27. At day 25, when the uterine P and PGE and PGF were high, massive intrauterine treatment with 500 microng PGF2alpha provoked only a sustained contracture on which only low level oscillation in IUP was superimposed. At day 26, when the P levels had decreased significantly (P less than 0.001) and the PG levels had not changed significantly, 50 microng PGF2alpha significantly increased cyclic IUP as compared with the day 25 value (P less than 0.001). At day 27, when the P levels decreased further, as little as 5 microng PGF2alpha provoked still higher cyclic IUP, in spite of a significant reduction in PG levels (P less than o.05). Stretching the uterus of six post partum and six 26 days pregnant rabbits (after removing the uterine contents) significantly increased the uterine PGF levels (P less than o.001). However, stretch increased only cyclic IUP of the post partum uterus and was without effect on the pregnant uterus, which still had high P levels. These results indicate that the myometrium is activated by exogenous PG or stretch, regardless of whether the uterine PG levels increase, remain unchanged or even moderately decrease, provided that the uterine P levels are reduced to a critical value.

Animals

Effects of nifedipine on myometrial activity and lower abdominal pain in women with primary dysmenorrhoea.

The effects of the calcium antagonist nifedipine on uterine activity and lower abdominal pain were studied during the first menstrual day in 10 women with severe primary dysmenorrhoea. Intrauterine pressure was recorded at three different levels by means of microtransducers. Nifedipine, 20 to 40 mg given orally, within 10 to 30 minutes effectively reduced the myometrial activity and relieved the pain. A moderate increase in heart rate, and a transient facial flushing were noted. In some patients receiving 30 or 40 mg this was associated with a slight headache. Otherwise no side effects were observed. It is suggested that calcium antagonists can be used to treat primary dysmenorrhoea and other conditions in which an inhibition of uterine activity is desirable.

Adolescent