The Differential Expression of Myometrial Connexin-43, Cyclooxygenase-1 and -2, and G s α Proteins in the Upper and Lower Segments of the Human Uterus during Pregnancy and Labor 1 (original) (raw)
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Endocrinology, 1997
We investigated the effects of uterine stretch on the levels of messenger RNA (mRNA) encoding the gap junction proteins connexin-43 (Cx-43) and connexin-26 (Cx-26) as well as the presence of gap junction plaques formed by Cx-43 within the myometrium. In nonpregnant ovariectomized rats, stretch of one uterine horn with a polyvinyl tube induced a significant increase in myometrial Cx-43 mRNA levels, an effect that was blocked by progesterone; no expression of Cx-26 was detected in the presence or absence of stretch. To investigate whether pregnancy and parturition modified the response to stretch, unilaterally pregnant rats underwent either sham operation or placement of a tube in the nongravid uterine horns. On day 20 of pregnancy, expression of Cx-43 mRNA in gravid horns was low, and stretch did not increase this level. Cx-26 mRNA expression was elevated at this time, but only in the gravid horns. Cx-43 mRNA was highly expressed in the myometrium of gravid horns during labor, but Cx-43 expression in sham-operated, nongravid horns remained low. In contrast, nongravid horns stretched with tubes expressed Cx-43 mRNA at levels similar to those in gravid horns. Levels of Cx-26 mRNA in gravid horns fell between days 20 and 23, and this was not altered by stretch. Punctate Cx-43 immunofluorescence (indicative of gap junction formation) also increased in the myometrium after uterine stretch and in gravid horns during labor. Our data demonstrate that differential mechanisms regulate the expression of Cx-43 and Cx-26 in the pregnant myometrium. Cx-43 expression during labor is dependent upon myometrial stretch under conditions of low progesterone. In contrast, Cx-26 expression during late pregnancy, although requiring the presence of the fetal/placental unit, does not require stretch of the myometrium.
Prostaglandins, 1996
The synthesis of prostaglandins in the uterus at term are modulated by two isoforms of the enzyme cyclooxygenase (COX): constitutive COX-1 and inducible COX-2. This study aims to characterize the expression of the protein for COX-1 and -2 in the rat uterus and cervix during the estrous cycle, pregnancy, and labor, and in cultured myometrial cells. Western immunoblotting of proteins was performed and quantitation of protein was obtained densitometrically. Results indicate: 1) the rat uteri, cervix, and isolated myometrial cells express both COX-1 and COX-2 proteins, 2) during pregnancy, both COX-1 and-2 increase, with a dramatic increase at parturition (250%–280%), 3) a 2-fold increase of cervical COX-2 is seen at spontaneous labor, 4) during proestrus and estrus, uterine expression of COX-2 is elevated, 5) both COX-1 and -2 were expressed by rat myometrial cells and treatment with IL-1β (10 ng/mL) produced a significant increase in COX-2, and 6) immunocytochemical studies show that both COX-1 and -2 were primarily localized to the epithelial cells of the endometrium and smooth muscle cells in the circular layers of the myometrium in the uterus and to the epithelial cells and smooth muscle cells in the cervix. Thus, we propose that increased expression of COX-2 may be involved at term in increased uterine contractility and cervical ripening.
Molecular Human Reproduction, 2000
Glutaredoxins are glutathione disulphide oxidoreductases catalysing disulphide reductions via a redox active disulphide. We have examined the presence of glutaredoxin in the human cervix, and its differential expression during cervical remodelling in term pregnancy and immediately post-partum as compared to the non-pregnant state. Cervical biopsies were obtained from 24 term-pregnant and 24 post-partal women, of which 10 were taken after spontaneous delivery, 10 after prostaglandin-induced delivery and four after mifepristone-induced delivery, all obtained within 15 min after delivery. Six non-pregnant women served as controls. The tissues were analysed for the glutaredoxin mRNA levels using a solution hybridization method. Glutaredoxin mRNA was expressed in the human cervix, the level increased ജ2-fold at term pregnancy and immediately postpartum. The level of cervical glutaredoxin mRNA from prostaglandin E 2 -treated women was 3-fold higher than after spontaneous ripening and delivery. Localization of glutaredoxin was visualized with immunohistochemistry in cervices from two post-partal women, and was compared to that of thioredoxin. We conclude that glutaredoxin may be involved in the regulation of cervical ripening in humans, particularly in the inflammatory reaction seen during this process. Glutaredoxin mRNA levels are up-regulated after prostaglandin treatment, which is effective and the most commonly used substance for cervical priming and induction of labour.
Endocrinology, 2000
Myometrial contractions of labor result from an increase in myometrial activation and stimulation. Activation develops through the expression of contraction associated proteins (CAPs), including oxytocin receptors (OTR), connexin-43 (Cx-43), and prostaglandin F 2␣ receptors (FP). Stimulation involves increases in contractile agonists including prostaglandin E 2 (PGE 2 ) and prostaglandin F 2␣ (PGF 2␣ ) that may result from increases in prostaglandin endoperoxide H synthase (PGHS)-2. A mouse model of preterm birth was used to study gene expression involved in myometrial activation and stimulation. To induce preterm birth, pregnant C57BL/6J mice were intubated with 6 g/kg ethanol on gestational day 16 and were killed every 6 h from treatment until birth. RIA was used to measure uterine PGE 2 and PGF 2␣ , while PGHS-2, OTR, Cx-43, and FP messenger RNA levels were measured by ribonuclease protection assay. Increases in CAP mRNA were associated with term and preterm birth. There were differences in stimulation effectors associated with preterm and term birth. Uterine PGF 2␣ values were increased only at the time of term birth, but PGE 2 was elevated during both preterm and term labor. These data suggest that existing levels of PGF 2␣ are sufficient for preterm birth when CAP expression is increased, but term labor requires increases in PGE 2 , PGF 2␣ , and CAPs. The PGHS-2 messenger RNA expression pattern suggests that it is a CAP.
Reproductive biology and endocrinology : RB&E, 2006
Prolonged labour is associated with greater morbidity and mortality for mother and child. Connexin 43 is a major myometrial gap junction protein found in human myometrium. Syndecan 3 seems to prevail in the human uterus among heparan sulphate proteoglycans, showing the most significant increase during labour. The aims of the present study were to investigate syndecan 3 and connexin 43 mRNA expressions and protein distributions in human uterine tissue during normal and prolonged labour. Uterine isthmic biopsies were collected from non-pregnant (n = 7), term pregnant women not in labour (n = 14), in normal labour (n = 7) and in prolonged labour (n = 7). mRNA levels of syndecan 3 and connexin 43 were determined by real time RT-PCR. The localization and expression were demonstrated by immunohistochemistry and confocal microscopy. In women with prolonged labour, the mRNA expressions of syndecan 3 and Connexin 43 were considerably lower than the expression level at normal labour (p < 0...
The Journal of Physiology, 2008
We have documented gestation-and labour-(preterm and term) dependent changes in expression of genes encoding contraction associated proteins in the rat uterus and correlated these changes with various parameters of uterine contractility. The data demonstrate increased expression of contractile agonist systems concurrent with decreased expression of relaxant systems after gestational day 20. Significant increases in expression of oxytocin (OT), its receptor (OTR), prostaglandin (PG) H synthase isoform 1 (PGHS-1) and PGF 2α receptor (FP) occurred first, followed by increases in PGHS-2, connexin-43, endothelin-1 (ET-1) and the ET-1 receptor isoform ET A. Expression of OTR and FP was significantly reduced during mid-gestation compared to non-pregnant animals. Expression of inducible nitric oxide synthase (iNOS) increased significantly during pregnancy then decreased concurrently with the increase in OTR and FP. Functional changes in uterine contractility accompany changes in gene expression. OT was the most potent contractile stimulant. Sensitivity of uterine strips to OT was reduced in early and mid-pregnancy then increased at uterine activation. Progesterone antagonist-induced preterm labour caused changes similar to those at normal term. Comparison of mRNA transcripts in separated endometrium and myometrium suggested that the endometrium is an important regulator of myometrial contractility, analogous to the relationship between endothelium and vascular smooth muscle. This novel combination of functional and genetic expression analyses provides new insight into the physiology of parturition.
Acta Obstetricia et Gynecologica Scandinavica, 2013
ObjectiveTo investigate expression and localization of prostaglandin receptors EP1‐4 and FP and localization of stromal factors CTGF (connective tissue growth factor), furin, calgranulin B and ALOX15 (arachidonate 15‐lipooxygenase) in human cervical tissue from post‐term women with failed or successful labor induction after prostaglandin priming.DesignExperimental prospective clinical study.SettingTertiary obstetric care center.PopulationTwenty‐six women giving birth post‐term, with failed or successful labor induction, and a control group consisting of 19 women with spontaneous onset of labor and delivery at term.MethodsBiopsies were obtained from post‐term women with successful (responders; R) and failed (non‐responders; NR) labor induction. Women with spontaneous delivery at term were included as controls (C). mRNA expression was determined with real time PCR, protein expression and localization with immunohistochemistry.Main outcome measuresComparisons of mRNA and protein expres...