Implications of the RhoA/Rho associated kinase pathway and leptin in primary uterine inertia in the dog.

The underlying functional and molecular changes in canine primary uterine inertia (PUI) are still not clarified. Leptin (Lep) and obesity negatively affect uterine contractility in women, partly mediated by the RhoA/Rho associated kinase pathway, affecting myometrial calcium sensitization. We hypothesized that increased uterine Lep/Lep receptor (LepR) or decreased RhoA/Rho associated kinase expression contributes to PUI in dogs, independent of obesity. Dogs presented for dystocia were grouped into PUI (n = 11) or obstructive dystocia (OD, still showing strong labor contractions; n = 7). Interplacental full-thickness uterine biopsies were collected during Cesarean section for relative gene expression (RGE) of RhoA, its effector kinases (ROCK1, ROCK2), Lep and LepR by qPCR. Protein and/or mRNA expression and localization was evaluated by immunohistochemistry and in situ hybridization. RGE was compared between groups by one-way ANOVA using body weight as covariate with statistical significance at P < 0.05. Uterine ROCK1 and ROCK2 gene expression was significantly higher in PUI than OD, while RhoA and Lep did not differ. LepR RGE was below the detection limit in five PUI and all OD dogs. Litter size had no influence. Lep, LepR, RhoA, ROCK1, ROCK2 protein and/or mRNA were localized in the myometrium and endometrium. Uterine protein expression appeared similar between groups. LepR mRNA signals appeared stronger in PUI than OD. In conclusion, lasting, strong labor contractions in OD likely resulted in downregulation of uterine ROCK1 and ROCK2, contrasting the higher expression in PUI dogs with insufficient contractions. The Lep-LepR system may affect uterine contractility in non-obese PUI dogs in a paracrine-autocrine manner.

Smooth muscle 22α deficiency impairs oxytocin-induced uterine contractility in mice at full-term pregnancy.

Smooth muscle 22α (SM22α, namely Transgelin), as an actin-binding protein, regulates the contractility of vascular smooth muscle cells (VSMCs) by modulation of the stress fiber formation. However, little is known about the roles of SM22α in the regulation of uterine contraction during parturition. Here, we showed that contraction in response to oxytocin (OT) was significantly decreased in the uterine muscle strips from SM22α knockout (Sm22α-KO) mice, especially at full-term pregnancy, which may be resulted from impaired formation of stress fibers. Furthermore, serious mitochondrial damage such as the mitochondrial swelling, cristae disruption and even disappearance were observed in the myometrium of Sm22α-KO mice at full-term pregnancy, eventually resulting in the collapse of mitochondrial membrane potential and impairment in ATP synthesis. Our data indicate that SM22α is necessary to maintain uterine contractility at delivery in mice, and acts as a novel target for preventive or therapeutic manipulation of uterine atony during parturition.

Relationship between uterine smooth muscular CPI-17-signal pathway-mediated Ca2+ sensitivity changes and uterine atony-induced postpartum haemorrhage.

This study aimed to investigate the changes of protein kinase C (PKC)-potentiated phosphatase inhibitor of 17 ku (CPI-17) expression, PKC activity and Rho kinase activity in the maternal uterine smooth muscle (USM), and their roles in the occurrence of uterine atony-induced postpartum haemorrhage (UAI-PPH). Sixty primiparaes who had a caesarean section performed were divided into the case group (with UAI-PPH) and the control group (the uterine contraction was good, without the PPH). The USM-p-CPI-17 (Thr38) protein levels, the activities of PKC and Rho kinase in the case group and the control group were 0.43 ± 0.20, 4.30 ± 0.91, 10.85 ± 1.70 and 0.67 ± 0.32, 0.099 ± 0.028, 0.20 ± 0.071, respectively (p < .05). The down-regulated expression of CPI-17 phosphorylated proteins might be one of the important factors of UAI-PPH, while the activity reduction of PKC and Rho kinase might be the reason that led to the phosphorylation level reduction of USM-CPI-17 in UAI-PPH. Impact Statement What is already known on this subject? The studies have shown that in the late pregnancy period, the total protein and phosphorylated protein of myometrial CPI-17 are significantly higher than in the non-pregnancy state, and they were all involved in regulating and enhancing the Ca2+ sensitivity of USMC during the pregnancy. The data regarding the CPI-17-signal pathway-mediated Ca2+ sensitivity in UAI-PPH is sparse. What do the results of this study add? We have shown that the down-regulated expression of CPI-17 phosphorylated proteins might be one of the important factors of UAI-PPH, while the activity reduction of PKC and Rho kinase might be the reason that led to the phosphorylation level reduction of USM-CPI-17 in UAI-PPH. What are the implications of these findings for clinical practice and/or further research? Further studies are needed to confirm the pathogenesis of CPI-17-signal pathway-mediated Ca2+ sensitivity in UAI-PPH.

Hemorragia obstétrica manejada con balón de Bakri / Obstetric hemorrhage management with the Bakri SOS balloon

Antecedentes: La Organización Mundial de la Salud reporta que existen en el mundo 536.000 muertes maternas al año, de las cuales 140.000 son originadas por hemorragia obstétrica, representando el 25% del total de dichas muertes. En México, se considera la segunda causa de muerte materna, con una tasa de mortalidad de 14,3 por 100.000 nacidos vivos. Objetivo: Conocer el porcentaje de éxitos de las pacientes con hemorragia obstétrica tratadas con balón de Bakri en el Instituto Nacional de Perinatología. Material y métodos: Se analizó una serie de casos, durante 2 años (2009-2011) en pacientes complicadas con hemorragia obstétrica, las cuales recibieron manejo conservador con balón de Bakri. Se encontró a 19 pacientes y se describieron los antecedentes obstétricos, personales, control prenatal, atención obstétrica, parámetros de laboratorios y desenlace perinatal. Resultados: El porcentaje de éxito con el balón de Bakri fue del 95% y solo el 5% se consideró fallido, ameritando histerectomía obstétrica. La pérdida hemática promedio fue 1.290 cc, con diferencia de 4 g/dl en los controles de hemoglobina pre- y posquirúrgicos. Dos días promedio de estancia en unidad de cuidados intensivos. El peso promedio de los recién nacidos fue 2.580 g y el 63% fue de sexo femenino. No se reportaron complicaciones por el uso del balón de Bakri. Se realizó una fórmula para estimar el llenado de balón en cc = 41 + (11 × semanas de gestación). Conclusión: El uso del balón de Bakri puede ser útil en el manejo conservador ante una hemorragia obstétrica con una tasa considerable de éxito y sin reportes de complicación debida al uso

Background: The World Health Organization reports that 536,000 maternal deaths occur per year, of which 140,000 are caused by obstetric hemorrhage, representing 25% of all maternal deaths. In Mexico, obstetric hemorrhage is the second cause of maternal death, with a mortality rate of 14.3/100,000 newborns. Objective: To describe the success rate in obstetric hemorrhage patients treated with the Bakri SOS balloon in the National Institute of Perinatology. Material and methods: From 2009- 2011, data were collected from obstetric hemorrhage patients (n = 19) who were treated conservatively with the Bakri SOS balloon in the Institute. Data on obstetric and personal history, prenatal care, obstetric care, laboratory values and perinatal outcomes were obtained. Results: The success rate with the Bakri SOS balloon was 95%, with a failure rate of only 5%; these patients required further hysterectomy. The mean blood loss was 1,290 cc, with a difference of 4 g of hemoglobin before and after surgery. The mean length of stay in the intensive care unit was 2 days. The mean birth weight was 2,580 g, and 63% of the neonates were females. There were no incidents or complications with the use of the Bakri SOS balloon. The formula to estimate balloon filling was cc = 41 + (11 × gestational age). Conclusion: The Bakri SOS balloon can be helpful to treat obstetric hemorrhage and has high success rates and no complications

[Morphological features of the myometrium in connective tissue dysplasia in women with uterine inertia].

OBJECTIVE: to reveal the morphological features of the lower uterine segment myometrium in connective tissue dysplasia (CTD) in women with uterine inertia. MATERIAL AND METHODS: Histological, immunohistochemical (with antibodies against collagen types I and III, matrix metalloproteinases 1 and 9 (MMR-1, MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), fibronectin; fibulin-5, connexin-43), electron microscopic, and electron immunocytochemical studies with morphometry of myometrial fragments from 15 parturient women with CTD and uterine inertia (a study group) and those from 10 women without CTD (a control group). RESULTS: The myometrium in CTD exhibited the decreased expression of connextin-43, fibulin-5, TIMP-1, collagens types I and III with collagen type III predominance and the unchanged levels of fibronectin and MMP-1 and MMP-9. Electron microscopy and immunocytochemistry showed fewer intercellular contacts and the dramatically lower expression of connexin-43 than in the control. CONCLUSION: A set of found myometrial changes in women with uterine inertia is a manifestation of CTD.

[The influence of nitric oxide generation on the production of interleukins and processes of prostaglandin synthesis in fetal membranes in spontaneous parturition and uterine inertia]. / Vliianie generatsii oksida azota na produktsiiu interleikinov i protsessy sinteza prostaglandinov v plodnykh obolochkakh pri spontannoi rodovoi deiatel'nosti i slabosti rodovykh sil.

62 women in 38-40 weeks gestation were examined, 37 of them had normal delivery, whereas others (25) with uterine inertia, had delivery by Cesarean section. In the fetal membranes preparations nitric oxide production, interleukins -1beta and -6, arachidonic acid content and phospholipase A2 activity (limiting the rate of prostaglandin biosynthesis) were examined. In the case of uterine inertia increase of nitric oxide generation, decrease of interleukins and arachidonic acid levels and phospholipase A2 activity was found. Modulation of nitric oxide production with inhibitors and activators allowed to emphasize the role of NO in regulation of cytokine response and control of initial stages of prostaglandins synthesis.

Application of electron spin resonance for evaluation of the level of free radicals in the myometrium in full-term pregnancy with normal labour and uterine inertia.

In order to identify and quantify free radicals in the tissues of patients with normal physiological and pathological states of births, we developed a method to evaluate the amount of free radicals in myometrium of subplacental area and from body of uterus, using electron spin resonance spectroscopy. Analysis of the concentration of free radicals in the myometrium in full-term pregnancy with normal labour and during uterine inertia was studied. The activities of Ca2+-ATPase, cytochrome c oxidase and succinate dehydrogenase in samples of these tissues were tested too. Low free radical concentrations in these tissues were associated with disturbances in contractile activity of myometrium along with reduction of Ca2+-ATPase, cytochrome c oxidase and succinate dehydrogenase activity. There proved to be an association between the level of free radicals in the tissues and alteration in the physiological processes.

[Lectin histochemistry of human placenta in the normal state and in uterine inertia]. / Lektinogistokhimiia platsenty cheloveka v norme i pri slabosti rodovoi deiatel'nosti.

The lectin-peroxidase technique has been used. The peanut lectin is able to label selectively Kashchenko--Hofbauer cells, villi of the chorion; the soya lectin--decidual cells in the maternal part of the placenta. Prolonged labour development is connected with disappearance of Kashchenko--Hofbauer cells, with a reduced binding of the Laburnum anagyroides lectin in combination with an intensified peanut lectin and concanavalin A binding with glycopolymeres of the villi of the chorion.

[ATPase activity and fluorescence of myometrial actomyosin in experimental uterine inertia]. / ATF-azna aktyvnist' ta fluorestsentsiia aktomiozinu miometriia za aksperymental'noï slabkosti polohovoï diial'nosti

A comparative study was performed for actomyosin complexes of the female rabbit myometrium in the state of labour (actomyosin of the control) and secondary uterine inertia (actomyosin of the model). Under the secondary uterine inertia the activity of actomyosin Ca2+- and Mg2+-ATPase decreases. When pH of the medium changes, ATPase of control actomyosin has two peaks of the activity: at rH 6.0 and pH 9.0, that of the model at pH 6.0. Actomyosin of the model and control differs by a degree and rate of superprecipitation, thermal stability and structure. It is supposed that the structural changes in actomyosin under the secondary uterine inertia occur due to accumulation of the metabolism products, the level of which with this pathology is beyond the limits of the adaptation potentialities of the organism.