Loss of myometrial oxytocin receptors during oxytocin-induced and oxytocin-augmented labour

Oxytocin is used widely for the induction and augmentation of labour, but there is little information about the dynamics of oxytocin receptors in human myometrium during parturition, and the possible effect of oxytocin infusion. This information is important because G protein-coupled receptors, such as the oxytocin receptor, undergo desensitization after prolonged or repeated stimulation. The concentration of myometrial oxytocin receptors and the steady state of its mRNA were measured in patients undergoing Caesarean sections before or during spontaneous or induced labour. The concentration of receptors before labour was 477 (175-641) fmol mg(-1) protein (median, quartile range), and decreased to 140 (72-206; P < 0.05) and 118 (69-75; P < 0.01) fmol mg(-1) protein during prolonged oxytocin-augmented and oxytocin-induced labour, respectively. The corresponding oxytocin receptor mRNA concentrations decreased by 60- and 300-fold, respectively. The decrease in receptor binding and mRNA in women receiving oxytocin infusion indicates that homologous receptor desensitization occurs in vivo.     

Influence of the oral administration of micronized progesterone on plasma and tissue levels of steroids in human pregnancy

A single dose of micronized progesterone, orally administered to women at different stages of pregnancy, induced an immediate increase in the plasma levels of progesterone. Progesterone was administered to another group of women just before elective cesarean section. Levels of progesterone, oestradiol-17 beta and oestrone were determined in plasma, placenta and at different sites of the myometrium obtained during the surgical procedure. Results were compared to those observed in a control group of women who did not receive progesterone. Progesterone levels demonstrated a marked increase in plasma and in the whole myometrium 150 min after administration; the levels then decreased rapidly to control values within one hour. The concentrations of progesterone in the placenta did not show any change. Evident modifications of the oestrogen levels appeared in the myometrium and in the placenta after the administration of progesterone whereas no change occurred in the plasma. No difference was observed in estradiol-17 beta in the myometrium whereas an increase was seen in the placenta. Estrone levels decreased in the myometrium and in the placenta. This study demonstrates a prompt delivery of an orally administered natural progesterone to the myometrial target tissue and subsequent modifications in the estrogen pattern. This provides a theoretical mechanism for the clinical use of progesterone in the prevention of premature labor.     

Tissue-specific concentration changes of estrone and estradiol during spontaneous and ACTH-induced parturition in sheep

Changes in estrogen production are considered important in the sequence of events leading to parturition. We sought tissue-specific changes in the concentration of unconjugated estrone (E1) and estradiol (E2) in intrauterine fetal (amnion, chorion) and maternal (endometrium, myometrium) tissues during normal pregnancy, labour, and ACTH-induced labour in sheep. The mean concentrations of E1 and E2 in the fetal membranes were higher than in endometrium and myometrium. In amnion there were no consistent changes in estrone concentrations with gestation, although estradiol concentrations increased between day 130 and term. In the endometrium there were increases in both estrone and estradiol between day 100 and term, whereas in the myometrium increases in the concentrations of E1 and E2 occurred between days 130-135 and term. Animals showing a labourlike pattern of uterine contractions after intrafetal ACTH administration did not show significant differences in estrone or estradiol concentrations in amnion, chorion, or endometrium compared with saline-infused controls. However, there was a progressive increase in the concentration of estrone and estradiol in the myometrium during ACTH-induced labour. We conclude that changes in the concentrations of estrone and estradiol in intrauterine tissues vary between the tissues studied and the two estrogens. In general, estrogen concentrations increased towards term, but this trend was more marked in the maternal than fetal tissues. The changes in estrone concentrations in myometrium, but not in the other tissues, were replicated during ACTH-induced labour. Our results would be compatible with the suggestion that tissue-specific changes in estrogen concentrations may contribute to the local intrauterine steroid milieu during pregnancy and at term.     

Inducing labour with vaginally administered prostaglandin E2.

In 50 consecutive pregnant women at a 125-bed community hospital with 1000 deliveries annually, labour was induced with prostaglandin E2 administered intravaginally. There were no stillbirths or neonatal deaths, and complications in the mothers were few. In nine women (18%) oxytocin was subsequently administered because of a failure of labour to progress; in spite of this, cesarean section was required in two (4%) of the patients. The overall cesarean section rate was 6%. Prostaglandins have been used routinely to induce labour in the United Kingdom for several years. This noninvasive method is safe, effective and well received by women in a community hospital setting, including those wanting "natural childbirth".     

Corticotropin-releasing hormone acts on CRH-R1 to inhibit the spontaneous contractility of non-labouring human myometrium at term

AIMS: Corticotropin-releasing hormone (CRH) has been implicated in the mechanisms controlling human parturition. The aims of the present study were to explore effects of CRH on contractility of human term myometrium and compare these effects in labouring and non-labouring myometrial strips. MAIN METHODS: The cumulative effects of CRH (10(-10) to 10(-7) mol/l) on the spontaneous contractility of labouring and non-labouring myometrial samples were evaluated using isometric tension recordings. KEY FINDINGS: CRH exhibited a concentration-dependent relaxant effect on spontaneous contractions in non-labouring term myometrium. This effect was mediated principally via a reduction in the amplitude rather than any changes in the frequency of contractions. The CRH-induced inhibitory effect on contractility could be blocked by pre-treatment with a CRH-R1 antagonist antalarmin, but not by pre-treatment with the CRH-R2 antagonist astressin 2B. CRH had no effect on spontaneous contractions in the labouring myometrium, as no change in either the amplitude or the frequency was observed. SIGNIFICANCE: Our findings indicate that CRH acts on CRH-R1 to inhibit spontaneous contractions in term myometrium from women who were not undergoing labour, but not those who were undergoing labour, supporting the hypothesis that CRH exerts dual effect on myometrium during pregnancy.     

Identification of calmodulin-like activity in term human amnion: effect of calmodulin inhibitors on prostaglandin biosynthesis

Human amnion prostaglandin E2 (PGE2) synthesis increases with the onset of labour, and this synthesis is Ca2+-dependent. To understand better the mechanism of Ca2+-stimulated PGE2 biosynthesis, studies were performed to identify the presence of the intracellular Ca2+-mediator, calmodulin, in human amnion and to examine its role in PGE2 synthesis. Calmodulin-like activity was identified by the ability of the microsomal and cytosolic fractions of the 105,000g centrifugation of amnion homogenate to stimulate cyclic AMP-dependent phosphodiesterase activity. Cytosolic fractions consistently stimulated phosphodiesterase activity more than microsomal fractions (P less than 0.001) in paired samples from term human amnions. This activity was calcium-dependent. The cytosolic and microsomal factors increased the Vmax but not the Km of phosphodiesterase. There were no differences in these parameters with the onset of labour. The distribution of calmodulin-like activity between microsomes and cytosol was similar to the distribution of calmodulin mass as determined by radioimmunoassay. Three structurally different inhibitors of calmodulin activity, calmidazolium, trifluoperazine and W7, were tested for their ability to inhibit cytosolic factor-stimulated phosphodiesterase activity and to inhibit PGE2 output from dispersed amnion cells obtained before the onset of labour at term (cesarean section cells) or after spontaneous labour and vaginal delivery (spontaneous labour cells). The 50% inhibitory concentrations of the calmodulin antagonists in the phosphodiesterase assay were: trifluoperazine (6.7 microM), calmidazolium (0.11 microM), and W7 (24 microM). Trifluoperazine inhibited both basal and calcium ionophore (A23187)-stimulated PGE2 output from cesarean section cells and spontaneous labour amnion cells. Calmidazolium inhibited basal PGE2 output in cesarean section cells and spontaneous labour cells, but had no effect on A23187-stimulated output. W7 inhibited only the ionophore-stimulated PGE2 output in cesarean section amnion cells. The rank order of inhibition of both phosphodiesterase activation and basal PGE2 output was: calmidazolium greater than trifluoperazine greater than W7. These results suggest that human amnion contains calmodulin and that its distribution, concentration and activity remain unchanged with the onset of labour. The data suggest, although not conclusively, that calmodulin may, in part, play a role in amnion cell PGE2 production. Further investigation of calmodulin effects upon specific enzymes in the PGE2 synthetic pathway will be necessary to elucidate a role for calmodulin in PGE2 production.     

Concentration of oxytocin receptors in the placenta and fetal membranes of cows during pregnancy and labour.

The concentrations of oxytocin receptors were measured in intercaruncular and caruncular endometrium, fetal cotyledons, chorioallantois and amnion during pregnancy and parturition in cows. Tissues were obtained on days 20 (endometrium only), 50, 100, 150, 200, 225, 250, 275, at term (days 280-284), during labour and within 24 h after calving. Receptor concentrations in intercaruncular endometrium were low on day 20 of pregnancy, 39 +/- 11 fmol mg-1 protein. By day 50, receptor concentrations had increased more than tenfold to 572 +/- 52 fmol and rose steadily until day 250 and then levelled off at about 4500 fmol mg-1. Shortly before parturition, on day 282 +/- 1, a further rise to 7300 +/- 1418 fmol mg-1 was observed, these concentrations were maintained throughout labour. By contrast, caruncular endometrial receptor concentrations remained low until term, mean 145 +/- 15 fmol mg-1, and then rose to 720 +/- 163 fmol mg-1 during labour (cervix 17 cm--fully dilated). Fetal cotyledons and membranes had very low oxytocin receptor concentrations during most of pregnancy, on average only 20 fmol mg-1 protein. At term and during labour, receptor concentrations were significantly increased in both tissues. Mean concentrations during labour were 163 +/- 36 fmol mg-1 for cotyledons, 270 +/- 61 fmol mg-1 for chorioallantois and 311 +/- 121 fmol mg-1 for amnion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Local and systemic control of myometrial contractile activity during labour in the sheep

The relative contribution of systemic versus local (intrauterine) factors in the activation and stimulation of the sheep myometrium during labour was examined using an in-vivo myometrial explant preparation. Myometrial tissue alone (MYO) or with attached endometrium (ENDO/MYO) was removed from the pregnant uterine horn, sutured to a stainless-steel frame and placed into the omental fat. After 7-10 days the explants developed a pattern of electromyographic activity qualitatively similar to that of the uterine myometrium. Induction of preterm labour by infusion of ACTH (66.6 ng/min for 15 min every 2 h) to the fetus resulted in a reduction in plasma progesterone concentrations and increases in values of oestradiol-17 beta and 13,14-dihydro 15-keto PGF-2 alpha in maternal plasma. The onset of labour, which followed these endocrine changes, was characterized by an increase in EMG burst frequency and reduction in burst duration occurring simultaneously in both the uterine myometrium and in the explants. The response of the uterine and explant myometrium to oxytocin also exhibited a parallel significant increase over the 24-h period leading to delivery. No differences were apparent between the explants containing myometrial tissue alone or those comprising endometrial and myometrial tissue. There was no significant change in uterine or explant EMG activity, or oxytocin responsiveness, after saline administration to the fetus. The pattern of EMG activity changes during spontaneous labour were not distinguishable from those during ACTH-induced labour. As with oxytocin, the responsiveness of the explants to electrical stimulation increased significantly at labour compared to pre-labour. These data suggest that factors within the systemic circulation play a major role in both the onset of labour contractions and the increased response to electrical or hormonal (oxytocin) stimulation during parturition in sheep.     

Labour-associated changes in the regulation of production of immunomodulators in human amnion by glucocorticoids, bacterial lipopolysaccharide and pro-inflammatory cytokines

Parturition is associated with changes in the production of inflammatory mediators by gestational tissues. An explant system was established to study the change in response of human amnion to various regulating factors during labour. Disks of tissue (6 mm) were excised from amnion membranes obtained either at term by Caesarian section before labour (n = 5-6) or after spontaneous vaginal delivery (n = 3-7). After 24 h equilibration in media, the tissues were treated with interleukin 1 beta (10 ng ml-1), tumour necrosis factor alpha (100 ng ml-1), lipopolysaccharide (5 micrograms ml-1) and dexamethasone (1 mumol l-1) or an appropriate vehicle control for 24 h (n = 3 wells per treatment). Media were harvested and interleukin 10, interleukin 6 and prostaglandin E2 concentrations were determined by immunoassay. In tissues taken both before and after the onset of labour, basal interleukin 10 production by amnion explants was near to the limit of detection. Basal production rates of PGE2 by amnion explants were significantly higher (P < 0.0012; Mann-Whitney U test) in tissues taken during labour than in tissues taken before the onset of labour, while interleukin 6 production was not significantly altered by labour. Production rates of interleukin 6 and prostaglandin E2 were significantly increased by interleukin 1 beta, tumour necrosis factor alpha and lipopolysaccharide in explants from tissues taken during and before labour, while the responsiveness of interleukin 10 production to these treatments was inconsistent. Dexamethasone had no effect on interleukin 6 production by amnion explants, but significantly inhibited prostaglandin E2 production, although this inhibition was approximately 30% lower in tissues obtained after the onset of labour. These results support the presence of inflammatory positive feedback cycles, coincident with a deficiency of an anti-inflammatory factor within gestational tissue, which may be involved in the progression or maintenance of labour.     

Diagnosis of dystocia and management with cesarean section among primiparous women in Ottawa-Carleton.

We carried out a chart review study to determine the rate of diagnosis of dystocia (abnormal progress) and the use of cesarean section to treat dystocia among 3887 primiparous women who gave birth to a single baby in the vertex presentation at four hospitals in Ottawa-Carleton in 1984. Of the 3740 women who had some labour 1127 (30.1%) were given a diagnosis of dystocia. Cesarean section for dystocia was done during all phases of labour (41% of procedures in the latent phase, 38% in the active phase and 21% in the second stage). The cesarean section rate varied among the hospitals from 11.8% to 19.6%. A total of 75% of the cesarean sections were for dystocia, disproportion or failed induction. The findings suggest that cesarean section is being done for disproportion without a trial of labour beyond the latent phase and for dystocia in the absence of fetal distress. If these practices were modified the cesarean section rate could be reduced from 16% to about 8%, the rate found in some other centres and that observed in Canada in the early 1970s.     

Prostaglandin concentrations in intra-uterine tissues from late-pregnant sheep before and after labour

Prostaglandin E (PGE), prostaglandin F (PGF) and 13,14-dihydro-15-keto-prostaglandin F (PGFM) have been measured in cotyledons and myometrium from sheep before and after labour. Fetal cotyledons contained more PGE than maternal cotyledons which in turn contained more than myometriu. The maternal cotyledon contained the highest concentrations of PGF, but the fetal cotyledon was the only tissue exhibiting a statistically significant rise in the concentration of PGF following labour. Concentrations of PGFM were closely correlated with (although usually lower than) those of PGF.     

Spontaneous oxidative DNA damage in bovine retained and nonretained placental membranes

Retention of fetal membranes (RFM) is believed to be associated with conditions of oxidative stress. In this study, 8-hydroxy-2'-deoxyguanosine (8-OH-dG) was used for the determination of spontaneous oxidative DNA lesions in maternal and fetal parts of bovine retained and nonretained placentas. Placental specimens were collected directly after spontaneous delivery or during cesarean section from cows divided into 6 groups: (A) cesarean section before term without RFM, (B) with RFM, (C) cesarean section at term without RFM, (D) with RFM, (E) spontaneous delivery at term without RFM and (F) with RFM. Isolated DNA was hydrolyzed and analyzed by HPLC; native nucleosides were monitored at 254 nm and 8-OH-dG by electrochemical detection. No significant differences in 8-OH-dG levels between retained and nonretained placental tissues were found in all samples from preterm groups (mean concentrations between 13 and 42 micromol/mol deoxyguanosine (dG)). In the term cesarean section group with RFM a significant increase in 8-OH-dG concentration in DNA from maternal (8-fold) and fetal (18-fold) membranes were detected when compared to the respective nonretained tissues. Also, in the term spontaneous delivery groups maternal nonretained placental tissues showed increased levels of 8-OH-dG in comparison to the respective tissues of the retained placenta group. In placental tissues oxidative DNA lesions appear to be controlled by responsive mechanisms which, possibly following exhaustion, give rise to increased 8-OH-dG levels.     

Relative abundance of human placental phospholipase A2 messenger RNA in late pregnancy.

The aim of this study was to determine messenger RNA (mRNA) levels for a specific phospholipase A2 (PLA2) in human placenta during late gestation prior to the onset of labour. The relative abundance of human placental mRNA for a nonpancreatic Group II PLA2 was determined using cDNA clone specific for this PLA2. Twenty seven placentae were collected from women undergoing elective (i.e. before the onset of labour) Caesarean section between 37 and 41 completed weeks gestation. The relative amount of human placental PLA2 mRNA did not change significantly over this period of late pregnancy (p greater than 0.8). Previously, we have demonstrated that placental PLA2 messenger RNA levels are increased in association with spontaneous onset labour at term in the human. The data obtained in this current study are consistent with the conclusion that the regulation of this human placental PLA2 gene is tightly controlled around the time of parturition and that its expression is increased acutely in association with labour.     

The effects of gestational age and intrafetal ACTH administration on the concentration of progesterone in the fetal membranes, endometrium, and myometrium of pregnant sheep

To examine the hypothesis that progesterone withdrawal from intrauterine tissues is a prerequisite to spontaneous labour or labour induced by administering ACTH to the ovine fetus, we measured the concentration of progesterone in amnion, chorion, endometrium, and myometrium of sheep at different stages of pregnancy and during ACTH-induced labour. There was no significant change in the concentration of progesterone nor in the progesterone:estradiol ratio in amnion or chorion in association with either spontaneous or ACTH-induced labour. The concentration of progesterone in endometrium rose significantly between days 50-60 and days 130-135 of gestation and decreased at term. There was also a fall in the progesterone:estradiol ratio in endometrium between days 130-135 and term. Neither the progesterone concentration not the progesterone:estradiol ratio changed in endometrium during ACTH-induced labour. In the myometrium the concentration of progesterone rose significantly between days 50-60 and day 100 of pregnancy and decreased between day 100 and days 130-135, with a further decline towards term. After intrafetal ACTH there was no change in the concentration of progesterone in the myometrium, although there was a fall in the progesterone:estradiol ratio. We conclude that labour occurring spontaneously at term is associated with a decrease in the progesterone concentration of maternal intrauterine tissues, the myometrium and endometrium. In contrast, there is no decline in the progesterone concentrations of the fetal membranes, the amnion and chorion.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relationship between fetal breathing movements and prostaglandin E2 during ACTH-induced labour in sheep

We measured fetal breathing movements and fetal carotid arterial prostaglandin E concentrations during adrenocorticotrophin-induced labour in 6 pregnant sheep and in 6 control animals starting at day 127. The 6 ACTH-treated animals went into labour on average 97 h after the onset of infusion and the incidence of fetal breathing movements diminished during the last 12h before the onset of labour. There was a significant negative relationship between the incidence of fetal breathing movements and fetal carotid arterial prostaglandin E concentrations (r = -0.88; P less than 0.001) in ACTH treated animals. These data suggest a role for prostaglandin E in the diminution of fetal breathing movements prior to the onset of labour.     

Expression of prostanoid receptors in human lower segment pregnant myometrium

Prostanoids, especially prostaglandin (PG) E(2), are important mediators of uterine relaxation and contractions during gestation and parturition. Inhibitors of PG formation as well as PG analogues are used to modulate uterine tonus. So far, only limited data are available regarding the expression of prostanoid receptors in human pregnant myometrium. In the present study, the expression of the receptors for PGE(2) (EP1, EP2, EP3, EP4), PGF(2alpha) (FP), prostacyclin (IP), and thromboxane A(2) (TP) in human pregnant myometrium was studied by RT-PCR, in situ hybridization and immunohistochemistry. Myometrial tissue was obtained from five women at term and not in labour and from two women who delivered preterm. Tissue specimens were excised from the upper edge of the transverse lower uterine segment incision. In all tissues analysed, EP1, EP2, EP3, EP4, FP, TP and IP receptor mRNA and protein was detected. mRNA expression for PGD(2) (DP) receptor was not detected in the majority of tissue specimens. EP1, EP2, EP4, IP, TP and FP receptor protein was detected on myometrial smooth muscle cells, whereas EP3 receptor protein was only expressed by stromal and endothelial cells. In situ hybridization experiments yielded similar results. The expression of the EP2 receptor mRNA was inversely related to gestational age. We suggest that the contractile effect of PGE(2) at term is probably mediated directly by the EP1 receptor expressed in myometrial smooth muscle cells and indirectly by the EP3 receptor expressed in stromal cells and a decrease in EP2 receptor expression.     

Human myometrial gene expression before and during parturition

Identification of temporal and spatial changes in myometrial gene expression during parturition may further the understanding of the coordinated regulation of myometrial contractions during parturition. The objective of this study was to compare the gene expression profiles of human fundal myometrium from pregnant women before and after the onset of labor using a functional genomics approach, and to further characterize the spatial and temporal expression patterns of three genes believed to be important in parturition. Fundal myometrial mRNA was isolated from five women in labor and five women not in labor, and analyzed using human UniGEM-V microarrays with 9182 cDNA elements. Real-time polymerase chain reaction using myometrial RNA from pregnant women in labor or not in labor was used to examine mRNA levels for three of the genes; namely, prostaglandin-endoperoxide synthase 2 (PTGS2), calgranulin B (S100A9), and oxytocin receptor (OXTR). The spatial expression pattern of these genes throughout the pregnant uterus before and after labor was also determined. Immunolocalization of cyclooxygenase-2 (also known as PTGS2) and S100A9 within the uterine cervix and myometrium were analyzed by immunohistochemistry. Few genes were differentially expressed in fundal myometrial tissues at term with the onset of labor. However, there appears to be a subset of genes important in the parturition cascade. The cellular properties of S100A9, its spatial localization, and dramatic increase in cervix and myometrium of women in labor suggest that this protein may be very important in the initiation or propagation of human labor.     

Amniotic fluid levels of tumor necrosis factor-alpha and soluble tumor necrosis factor receptor 1 before and after the onset of labor in normal pregnancies.

Tumor necrosis factor-alpha (TNF-alpha) is present in human placental and uterine cells and promotes the regulation of trophoblast growth and invasion. Tumor necrosis factor receptor 1 (TNF-R1) is a receptor for TNF-alpha, and soluble TNF-R1 (sTNF-R1) is present in amniotic fluid after receptor shedding. We evaluated whether amniotic fluid TNF-alpha and sTNF-R1 levels during labor differed from those before the onset of labor in normal pregnancies. This study enrolled 34 Japanese women experiencing normal pregnancies with single fetuses who had no infection. Of these subjects, 17 went into labor and had subsequent term deliveries (the labor group), and the other 17 underwent cesarean section without labor (the nonlabor group). The average gestational age at entry was 38-39 weeks of gestation. Maternal ages and gestational ages did not differ significantly between the two groups. Amniotic fluid was collected and the TNF-alpha and sTNF-R1 levels were determined by the ELISA method. Each of these levels was compared between the two groups. There was a significant increase in amniotic fluid TNF-alpha levels in the labor group. However, amniotic fluid sTNF-R1 levels did not differ significantly between the two groups. Amniotic fluid TNF-alpha may promote the onset of labor at term and/or term labor contributing to subsequent delivery may induce the production and secretion of TNF-alpha into the amniotic cavity. There was no pregnancy-associated increase in receptor shedding or cell apoptosis at the onset of labor.     

Myometrial immune cells contribute to term parturition,preterm labour and post‐partum involution in mice

This study aimed to determine the mechanism of uterine activation during labour, both term (TL) and preterm (PTL). We hypothesized that the peripheral leucocytes are recruited to uterine tissues by locally produced cytokines where they contribute to the initiation of parturition. Mouse uteri were collected (i) during gestation, TL and post‐partum (PP), (ii) during PTL initiated by intrauterine infusion of LPS (125 μg) or (iii) injection of the progesterone receptor antagonist RU486 and analysed for multiple cytokine expression levels by real‐time polymerase chain reaction (RT‐PCR) and 23‐plex Cytokine assay or enzymatically dispersed for assessment of immune cell populations. Markers of myeloid cell differentiation (Gr1, Neu7/4 and F4/80) were evaluated by FACS to define tissue macrophages (Macs), monocytes (M) and neutrophils (N) and by immunohistochemistry to detect tissue Macs and N. Our results indicate that: (1) Macs were elevated in mouse myometrium before TL (P < 0.05) followed by an increase in M and N; these changes were accompanied by an increase in multiple pro‐inflammatory cytokines/chemokines genes. The expression of corresponding proteins increased PP. (2) TL and RU486‐PTL models showed similar gene/protein expression profiles, (3) LPS‐PTL was characterized by strong pro‐inflammatory response and massive influx of N in myometrial tissues showing a pattern different from TL and RU486‐PTL, (4) The PP period appears similar in all three models, with elevated myometrial cytokine levels and high infiltration of immune cells. We concluded that leucocytes infiltrate myometrium around the time of parturition implicating their potential role in labour activation (both term and preterm) and major role in PP uterine involution.