Rat Uterine Research Articles

Tocolytic activity of the Lippia alba essential oil and its major constituents, citral and limonene, on the isolated uterus of rats

The species Lippia alba (Mill.) N. E. Brown belongs to the Verbenaceae family. It is abundant and grows spontaneously throughout the Brazilian territory. Popularly known as “erva-cidreira”, it is widely used because of its sedative, carminative and analgesic properties. The objective of this study was to investigate the mechanism of action of the L. alba essential oil (EOLa) and its major constituents citral and limonene, on isolated rat uterus muscle. To evaluate the EOLa, citral and limonene effect, cumulative concentrations curves for EOLa and citral (1–600 μg/mL) and for limonene (1–1200 μg/mL) were constructed from contractions of rat uterine strips under a 1 g tension. EOLa, citral and limonene dose-dependently relaxed myometrial preparations pre-contracted with 60 mM KCl, 10-2 IU/mL oxytocin, serotonin (10 μM), or ACh (10 μM). The results demonstrate that the EOLa, citral and limonene cause relaxation of the uterine smooth muscle. These results suggest that the relaxation induced by EOLa, citral and limonene is caused by inhibition of L-type VOCC, inhibiting the Ca2+ current through these channels, although other mechanisms of action are likely to contributing to relaxant activity. There was no involvement of K+ channels (BKca, KATP, KV) or cyclooxygenase on the relaxation promoted by EOLa. Then studies of the tocolytic effects of EOLa, citral and limonene may yield new insights into their therapeutic use.

Особенности структурно-функциональных преобразований миометрия межплацентарных зон рогов матки крыс в период гестации

Особенности структурно-функциональных преобразований миометрия межплацентарных зон рогов матки крыс в период гестации

A computational model of excitation and contraction in uterine myocytes from the pregnant rat

Aberrant uterine myometrial activities in humans are major health issues. However, the cellular and tissue mechanism(s) that maintain the uterine myometrium at rest during gestation, and that initiate and maintain long-lasting uterine contractions during delivery are incompletely understood. In this study we construct a computational model for describing the electrical activity (simple and complex action potentials), intracellular calcium dynamics and mechanical contractions of isolated uterine myocytes from the pregnant rat. The model reproduces variant types of action potentials – from spikes with a smooth plateau, to spikes with an oscillatory plateau, to bursts of spikes – that are seen during late gestation under different physiological conditions. The effects of the hormones oestradiol (via reductions in calcium and potassium selective channel conductance), oxytocin (via an increase in intracellular calcium release) and the tocolytic nifedipine (via a block of L-type calcium channels currents) on action potentials and contractions are also reproduced, which quantitatively match to experimental data. All of these results validated the cell model development. In conclusion, the developed model provides a computational platform for further investigations of the ionic mechanism underlying the genesis and control of electrical and mechanical activities in the rat uterine myocytes.

Bisphenol A decreases the spontaneous contractions of rat uterus in vitro through a nitrergic mechanism.

Bisphenol A (BPA), a chemical used in the manufacture of plastics, has toxic effects on various systems of the human body including the reproductive system. BPA possesses estrogenic activity and is implicated in altering oogenesis, ovulation, and fertility. In addition to ovulatory changes, uterine contractility is an important factor for fertility. However, the effects of BPA on myometrial contractions are not known. Therefore, we examined the effect of BPA on rat uterine contractions. The uterus was isolated from adult rats showing estrous phase, and spontaneous in vitro contractions were recorded (35±1 °C). The effect of cumulative concentrations of BPA was determined. Further, the involvement of nitric oxide (NO) and guanylyl cyclase (GC) for the BPA-induced changes on uterine contractility was evaluated using the NO synthase inhibitor (L-NAME) or GC inhibitor (methylene blue). BPA decreased the amplitude and frequency of spontaneous uterine contractions in a concentration-dependent manner. A decrease of 50% occurred at 1 and 3 μM for amplitude and frequency, respectively. L-NAME (N-ω-nitro-l-arginine methyl ester) blocked the BPA-induced decrease in amplitude at all concentrations but antagonized the frequency only at the maximum concentration (10 μM). Methylene blue (a GC inhibitor) did not block the BPA-induced responses but for the frequency at 10 μM of BPA. The results indicate that BPA decreased the amplitude and frequency of spontaneous uterine contractions by involving the nitrergic mechanism; however, the GC mechanism is not involved in the depression.

Preparation of rat uterine decellularized scaffold and extracellular matrix hydrogel

The chemical extraction method was used to prepare the rat uterine decellularized scaffolds, and to investigate the feasibility of preparing the extracellular matrix (ECM) hydrogel. The rat uterus were collected and extracted by 1%sodium dodecyl sulfate (SDS), 3% TritonX-100 and 4% sodium deoxycholate (SDC) in sequence. Scanning electron microscopy, histochemical staining and immunohistochemistry was used to assess the degree of decellularization of rat uterine scaffold. The prepared decellularized scaffold was digested with pepsin to obtain a uterine ECM hydrogel, and the protein content of ECM was determined by specific ELISA kit. Meanwhile, the mechanical characteristic of ECM hydrogel was measured. The results showed that the chemical extraction method can effectively remove the cells effectively in the rat uterine decellularized scaffold, with the ECM composition preserved completely. ECM hydrogel contains a large amount of ECM protein and shows a good stability, which provides a suitable supporting material for the reconstruction of endometrium in vitro.

Focal Adhesion Proteins, Vinculin and Integrin β5, During Early Pregnancy in Rat Uterine Epithelial Cells: Anastrozole Favors their Normal Distribution

Focal Adhesion Proteins, Vinculin and Integrin β5, During Early Pregnancy in Rat Uterine Epithelial Cells: Anastrozole Favors their Normal Distribution

Effects of the Aqueous Extract of Cnestis Ferruginea on the Histological Structure of Female Rat Ovary and Uterine Horns

Effects of the Aqueous Extract of Cnestis Ferruginea on the Histological Structure of Female Rat Ovary and Uterine Horns

The impact of obesity on pregnant rat uterine contractility: The roles of kisspeptin

The impact of obesity on pregnant rat uterine contractility: The roles of kisspeptin

Mechanisms of butylidenephthalide for twitch facilitation in electrically stimulated mouse vas deferens

Context: The rhizome of Ligusticum chuaxiong Hort. (Umbelliferae) has been used by Chinese for several thousand years. Its main constituent, butylidenephthalide (Bdph), was proved to be active in inhibiting rat uterine contractions induced by prostaglandin F2α and was reported to be a nonspecific antispamodic and a blocker of voltage-dependent Ca2+ channels (VDCCs).Objectives: The present study investigates the mechanisms of Bdph for twitch facilitation in ICR mouse vas deferens (MVD).Materials and methods: Electrical field stimulation (EFS, supramaximal voltage ranging from 60–90 V, 1 ms, 0.2 Hz) was applied to the isolated MVD in Krebs solution. Interactions between Bdph (50 µM) and calcium antagonist (verapamil, diltiazem or aspaminol) on the EFS-evoked twitch responses were determined. The number of experiments was 3–18.Results: Bdph (50 µM)-induced twitch facilitations from 100 to 391.9% were unrelated to activation of postjunctional cholinergic or adrenergic receptors. Verapamil and Bdph unabolished the twitch facilitation each other. Diltiazem unabolished the Bdph-induced twitch facilitation. In contrast, Bdph abolished those induced by diltiazem. Aspaminol at 20 μM abolished the Bdph-induced twitch facilitation. In contrast, Bdph abolished those induced by aspaminol. Tetraethylammonium and 4-aminopyridine, the K+ channel blockers, significantly augmented the Bdph-induced twitch facilitation.Discussion and conclusions: Bdph may bind to the different, more and same subtypes of VDCCs from verapamil, than diltiazem, and as aspaminol does on prejunctional membrane, respectively. Besides a blocker of VDCCs, Bdph may be a blocker of K+ channels on prejunctional membrane. Thus, Bdph depolarized the membrane and facilitated the cumulative Ca2+-induced twitch responses.

Effects of newly synthetized isoquinoline derivatives on rat uterine contractility and ROCK II activity

Protein kinases have an important role in signal transduction in the cellular system via protein phosphorylation. RhoA activated Rho-kinases have a pivotal role in the regulation of smooth muscle contraction. ROCK I and ROCK II phosphorylate myosin-phosphatase and myosin-kinase, which induces contraction in the myometrium. Several studies have investigated the affinity of isoquinoline alkaloids (HA-1077, H1152P) to Rho-kinases, and these compounds notably inhibited the Ca2+-independent process.We measured the efficiency of 25 original, newly synthesized isoquinoline derivatives for the Rho-kinase activity using Rho-associated kinase activity assay and determined their effects on the non-pregnant, 20-day pregnant and parturient rat myometrial contraction in vitro.The IC50 values of 11 from among the 25 derivatives were significantly lower on the oxytocin-induced non-pregnant rat uterine contraction compared with Y-27632 and fasudil, although their maximal inhibitory effects were weaker than those of Y-27632 and fasudil. We measured the effects of 11 isoquinoline molecules with significant IC50 values on ROCK II activity. We found two isoquinolines out of 11 compounds (218 and 852) which decreased the active ROCK II level similarly as Y-27632. Then we found that 218 and 852 relaxed the 20th-day pregnant and parturient rat uterus with greater potency as compared with fasudil.The majority of the synthesized isoquinoline derivatives have uterus relaxant effects and two of them significantly suppress the Rho-kinase mediated myosin light chain phosphorylation. Our results may suggest that the isoquinoline structure has a promising prospect for the development of new and effective inhibitors of uterine contractions in preterm birth.

Development of an in vitro model to study uterine functions and early implantation using rat uterine explants.

This study was conducted to develop an in vitro model using rat uterine explants to explore complex uterine functions. Rat uterine explants (1-2mm) were isolated, cultured and further characterized. Steroid hormone treatment of cultured explants showed that both Muc1 and Pr were significantly up-regulated (P<0.05) by E2. Areg was significantly up-regulated (P<0.05) by P4 and Igfbp1 was significantly up-regulated (P<0.05) by the combination of E2 and P4, although, in rat, Igfbp1 is E2-dependent. In vitro decidualization of cultured explants was induced and two potential markers of decidualization, Prl8a2 and Bmp2, were examined. Real-time quantitative PCR data revealed that both Prl8a2 and Bmp2 were significantly up-regulated (P<0.05) in MPA- and db-cAMP-treated explants compared to the control group of explants. Then, an individual hatched blastocyst and cultured explant was placed in a 96-well(round-bottom U-shaped) plate. Co-culture results showed that stable attachments were observed after 48h, where embryos were stably attached to the explants and could not be dislodged after mild shaking and/or pipetting. The rates of attachment of embryos to the explants were increased significantly in the P4-treated group (63.6%) compared to the control group (35.5%), after steroid hormone treatment. The rates of attachment were reduced significantly in the E2-treated group (0.0%), where no stable attachments were observed. Despite the necessity of comprehensive investigation, our results suggest that the cultured rat uterine explants can be a useful in vitro model to study uterine functions and early implantation.

Selective Estrogen Receptor Modulator (SERM)-like Activities of Diarylheptanoid, a Phytoestrogen from Curcuma comosa, in Breast Cancer Cells, Pre-osteoblast Cells, and Rat Uterine Tissues.

Diarylheptanoids from Curcuma comosa, of the Zingiberaceae family, exhibit diverse estrogenic activities. In this study we investigated the estrogenic activity of a major hydroxyl diarylheptanoid, 7-(3,4 -dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene (compound 092) isolated from C. comosa. The compound elicited different transcriptional activities of estrogen agonist at low concentrations (0.1-1 μM) and antagonist at high concentrations (10-50 μM) using luciferase reporter gene assay in HEK-293T cells. In human breast cancer (MCF-7) cells, compound 092 showed an anti-estrogenic activity by down-regulating ERα-signaling and suppressing estrogen-responsive genes, whereas it attenuated the uterotrophic effect of estrogen in immature ovariectomized rats. Of note, compound 092 promoted mouse pre-osteoblastic (MC3T3-E1) cell differentiation and the related bone markers, indicating its positive osteogenic effect. Our findings highlight a new, nonsteroidal, estrogen agonist/antagonist of catechol diarylheptanoid from C. comosa, which is scientific evidence supporting its potential as a dietary supplement to prevent bone loss with low risk of breast and uterine cancers in postmenopausal women.

Umbilical cord-derived mesenchymal stem cells on scaffolds facilitate collagen degradation via upregulation of MMP-9 in rat uterine scars

BackgroundSevere injuries of the uterus may trigger uterine scar formation, ultimately leading to infertility or obstetrical complications. To date, few methods have adequately solved the problem of collagen deposition in uterine scars. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have shown great promise in clinical applications. The objective of this study was to investigate the effect of a scaffold/UC-MSCs construct on collagen degradation and functional regeneration in rat uterine scars following full-thickness excision of uterine walls.MethodsIn order to establish a rat model of uterine scars, the uterine wall of approximately 1.0 cm in length and 0.5 cm in width (one-third of the uterine circumference) was excised from each uterine horn. A total of 128 scarred uterine horns from 64 rats were randomly assigned to four groups, including a PBS group (n = 32 uterine horns), scaffold group (n = 32 uterine horns), UC-MSCs group (n = 32 uterine horns) and scaffold/UC-MSCs group (n = 32 uterine horns) to investigate the effect of different treatments on the structure and function of uterine scars. PBS, degradable collagen fibres, UC-MSCs or UC-MSCs mixed with gelatinous degradable collagen fibres were injected into four pre-marked points surrounding each uterine scar, respectively. At days 30 and 60 post-transplantation, a subset of rats (n = 8 uterine horns) from each group was euthanized and serial sections of uterine tissues containing the operative region were prepared. Haematoxylin-eosin staining, Masson’s trichrome staining, and immunohistochemical staining for MMP-2, MMP-9, α-SMA and vWF were performed. Finally, another subset of rats (n = 16 uterine horns) from each group was mated with male rats at day 60 post-transplantation and euthanized 18 days after the presence of vaginal plugs to check numbers, sizes and weights of fetuses, as well as sites of implantation.ResultsThe scaffold/UC-MSCs group exhibited obvious collagen degradation compared with the other three groups. At day 60 post-transplantation, the number of MMP-9-positive cells in the scaffold/UC-MSCs group (25.96 ± 3.63) was significantly higher than that in the PBS group (8.19 ± 1.61, P < 0.01), the scaffold group (7.25 ± 2.17, P < 0.01) and the UC-MSCs group (8.31 ± 2.77, P < 0.01). The pregnancy rate in the scaffold/UC-MSCs group (10/16) was also significantly higher than that in the PBS group (2/16, P < 0.017), the scaffold group (1/16, P < 0.017) and the UC-MSCs group (3/16, P < 0.017).ConclusionsThe scaffold/UC-MSCs system facilitated collagen degradation in uterine scars via upregulation of MMP-9, which was secreted by transplanted UC-MSCs, and promoted regeneration of the endometrium, myometrium and blood vessels in uterine scars. Furthermore, the scaffold/UC-MSCs-treated uterine scars showed nearly complete restoration of receptive fertility.

Chronic ingestion of bisphenol A decreases the cholinergically evoked and spontaneous contractions of rat uterus in vitro

Background: Bisphenol A (BPA), a chemical used in the manufacture of plastics, has toxic effects on reproductive, developmental, and metabolic systems. It is implicated as a causative factor for infertility. The uterine and tubal contractility play a vital role in fertilization and implantation of zygote. The chronic exposure to BPA on myometrial contractions is not known. Aims and Objectives: The aim of this study is to examine the effect of chronic ingestion of BPA on rat uterine contractions evoked by acetylcholine. Materials and Methods: Rats weighing 90-150 g were fed BPA (2 μg/kg/day) or placebo containing pellets (time-matched control; TMC) orally for 28 days. The contractility of the uterus was also assessed in group of rats at the beginning (initial control [IC]). After 28 days, animals showing estrous phase were chosen for in vitro recording of uterine contractions (35 ± 1°C). Evoked contractions to different concentrations of acetylcholine were recorded followed by the effect on spontaneous contractions. Results: Acetylcholine evoked uterine contractions in vitro in a concentration-dependent manner. The contractions were similar in magnitude in IC and TMC. The uterus from BPA-fed animal exhibited decreased responsiveness to acetylcholine-evoked contractions as compared to TMC. In the presence of acetylcholine, frequency and force of spontaneous contractions increased in a concentration-dependent manner. However, in BPA-fed group, the frequency and force of spontaneous contractions were significantly attenuated. Conclusions: The results indicate that chronic exposure to BPA decreased the acetylcholine-evoked contractions as well as the spontaneous uterine contractions. The decreased contractility may account for the infertility seen after exposure to BPA.

Effects of ZD7288, a hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker, on term-pregnant rat uterine contractility in vitro

The uterus is a myogenic organ that is able to produce discrete spontaneous action potentials and contractions without any stimuli. Myometrial excitability is governed by ion channels including Ca+2 and K+ channels, but whether or not other channels such as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which play an important role in regulating cellular excitability, are also involved has not been reported in uterine smooth muscles. The aim of the present study was to examine whether blocking HCN channels with a specific blocker ZD7288 would modulate the uterine contractility in a rat model. Using longitudinal uterine strips from term-pregnant rats, the effects of varying concentrations of ZD7288 (50 μM, 100 μM, and 200 μM) were examined on uterine contractions generated spontaneously or by oxytocin (5 nmol/L) and on uterine strips depolarized by high-KCl (60 mM/L), or activated by L-type Ca2+ channels agonist (Bay K8644; 1 μM). Application of ZD7288 at concentrations of 200 μM and 100 μM, but not 50 μM, significantly decreased the amplitude of spontaneous uterine contractions. In addition, 200 μM of ZD7288 significantly reduced the force of contractions induced by oxytocin with a pronounced reduction while the tissues were depolarized by high-KCl solution, or activated by Bay K8644. The present study provides pharmacological evidence suggesting that pregnant uterine contractility is modulated by HCN channels and that these channels might represent a therapeutic target for controlling premature activation of uterine activity associated with preterm labor.

Oncogenic effects of urotensin-II in cells lacking tuberous sclerosis complex-2.

Lymphangioleiomyomatosis (LAM) is a destructive lung disease that can arise sporadically or in adults suffering from the tumor syndrome tuberous sclerosis complex (TSC). Microscopic tumors (‘LAM nodules’) in the lung interstitium arise from lymphatic invasion and metastasis. These consist of smooth muscle-like cells (LAM cells) that exhibit markers of neural crest differentiation and loss of the tumor suppressor protein ‘tuberous sclerosis complex-2’ (TSC2). Consistent with a neural phenotype, expression of the neuropeptide urotensin-II and its receptor was detected in LAM nodules. We hypothesized that loss of TSC2 sensitizes cells to the oncogenic effects of urotensin-II. TSC2-deficient Eker rat uterine leiomyoma ELT3 cells were stably transfected with empty vector or plasmid for the expression of TSC2. Urotensin-II increased cell viability and proliferation in TSC2-deficient cells, but not in TSC2-reconstituted cells. When exposed to urotensin-II, TSC2-deficient cells exhibited greater migration, anchorage-independent cell growth, and matrix invasion. The effects of urotensin-II on TSC2-deficient cells were blocked by the urotensin receptor antagonist SB657510, and accompanied by activation of Erk mitogen-activated protein kinase and focal adhesion kinase. Urotensin-II-induced proliferation and migration were reproduced in TSC2-deficient human angiomyolipoma cells, but not in those stably expressing TSC2. In a mouse xenograft model, SB657510 blocked the growth of established ELT3 tumors, reduced the number of circulating tumor cells, and attenuated the production of VEGF-D, a clinical biomarker of LAM. Urotensin receptor antagonists may be selective therapeutic agents for the treatment of LAM or other neural crest-derived neoplasms featuring loss of TSC2 or increased expression of the urotensin receptor.

MTORC1-mediated downregulation of COX2 restrains tumor growth caused by TSC2 deficiency.

Tuberous sclerosis complex (TSC), caused by loss-of-function mutations in the TSC1 or TSC2 gene, is characterized by benign tumor formation in multiple organs. Hyperactivation of mammalian target of rapamycin complex 1 (mTORC1) is the primary alteration underlying TSC tumors. By analyzing Tsc2-null mouse embryonic fibroblasts (MEFs) and rat uterine leiomyoma-derived Tsc2-null ELT3 cells, we detected evidence for the involvement of cyclooxygenase 2 (COX2) as a downstream target of mTORC1 in the development of TSC tumors. We showed that loss of TSC2 led to decreased COX2 expression through activation of an mTORC1/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Overexpression of COX2 promoted proliferation and tumoral growth of Tsc2-null cells. COX2 knockdown inhibited the proliferation of the control cells. COX2 enhanced Tsc2-null cell growth through upregulation of interleukin-6 (IL-6). In addition, rapamycin in combination with celecoxib, a COX2 inhibitor, strongly inhibited Tsc2-deficient cell growth. We conclude that downregulation of COX2 exerts a protective effect against hyperactivated mTORC1-mediated tumorigenesis caused by the loss of TSC2, and the combination of rapamycin and celecoxib may be an effective new approach to treating TSC.

The effects of estrogen on the α2-adrenergic receptor subtypes in rat uterine function in late pregnancy in vitro.

AimTo assess the effect of 17β-estradiol pretreatment on the function and expression of α2- adrenergic receptors (ARs) subtypes in late pregnancy in rats.MethodsSprague-Dawley SPD rats (n = 37) were treated with 17β-estradiol for 4 days starting from the 18th day of pregnancy. The myometrial expression of the α2-AR subtypes was determined by real time polymerase chain reaction and Western blot analysis. In vitro contractions were stimulated with (-)-noradrenaline, and its effect was modified with the selective antagonists BRL 44408 (α2A), ARC 239 (α2B/C), and spiroxatrine (α2A). The cyclic adenosine monophosphate (cAMP) accumulation was also measured. The activated G-protein level was investigated by guanosine 5′-O-[gamma-thio]triphosphate (GTPγS) binding assay.Results17β-estradiol pretreatment decreased the contractile effect of (-)-noradrenaline via the α2-ARs, and abolished the contractile effect via the α2B-ARs. All the α2-AR subtypes’ mRNA was significantly decreased. 17β-estradiol pretreatment significantly increased the myometrial cAMP level in the presence of BRL 44408 (P = 0.001), ARC 239 (P = 0.007), and spiroxatrine (P = 0.045), but did not modify it in the presence of spiroxatrine + BRL 44408 combination (P = 0.073). It also inhibited the G-protein-activating effect of (-)-noradrenaline by 25% in the presence of BRL 44408 + spiroxatrine combination.ConclusionsThe expression of the α2-AR subtypes is sensitive to 17β-estradiol, which decreases the contractile response of (-)-noradrenaline via the α2B-AR subtype, and might cause changes in G-protein signaling pathway. Estrogen dysregulation may be responsible for preterm labor or uterine inertia via the α2-ARs.

Mechanism of vascular dysfunction due to circulating factors in women with pre-eclampsia.

Circulating factors have been proposed to play a major role in the pathophysiology of endothelial dysfunction in pre-eclampsia (PE), which is defined as new-onset hypertension with proteinuria after 20 weeks of gestation. However, the mechanisms leading to altered vascular reactivity remain unclear. We hypothesized that circulating factors lead to endothelial dysfunction by increasing oxidative stress and reducing nitric oxide (NO) and prostaglandin (PG) bioavailability. Pregnant rat uterine and mesenteric arteries were incubated overnight with 3% normotensive (NP) or PE plasma collected from women upon admission to hospital. Responses to methacholine (MCh) were obtained using wire myography to assess endothelial function pathways. Vascular superoxide level was measured via dihydroethidium staining and nitric oxide synthase (NOS) expression via Western blots. PE plasma significantly increased superoxide levels and impaired endothelial dysfunction in uterine arteries (Emax 79.9±5.6% compared with 44.9±6.3%, P=0.0004), which was restored in the presence of oxidant scavengers or PG synthesis inhibition. Uterine artery vasodilation was abolished in the presence of pan-NOS inhibitor (P<0.0001) in both NP- and PE-treated vessels, but inducible nitric oxide synthase (iNOS)-dependent vasodilation was present only in NP-treated arteries. Uterine arteries exposed to PE plasma exhibit an increased endothelial NOS expression and a decreased iNOS expression. PE plasma did not alter endothelial function in mesenteric arteries, suggesting that the effect of circulating factors was vascular-bed-specific. We have shown that circulating factors lead to endothelial dysfunction via altered oxidative stress and vasodilator pathways. The present study contributes to our understanding of the pathophysiology and finding a potential target for intervention in PE.

Spasmodic versus spasmolytic activities of Euphorbia spinidens extract on rat isolated uterus.

Preterm contraction of uterus is a main cause of miscarriages and preterm labour. Euphorbia known as Ferphion in Iranian traditional medicine texts like Al-Hawi, is reported for prevention of preterm labour. Therefore, the objective of this research was to investigate the effect of Euphorbia spinidens Bornm. Ex Prokh. on motility of rat uterus. Uterine horns were isolated form non-pregnant female rats pretreated with estrogen. E. spinidens hydroalcoholic extract was examined on KCl (80 mM) induced and spontaneous periodic contraction in isolate uterine strips suspended in an organ bath and compared with nifedipine and ritodrine. In isolated rat uterine strips, E. spinidens extract (1-500 µg/mL) showed mixed effects. At lower concentrations, firstly potentiated the spontaneous periodic contraction, while in concentrations above 256 µg/mL the spontaneous periodic contractions were completely attenuated. These findings demonstrated that although lower concentrations of hydroalcoholic extract potentiated the spontaneous periodic contraction of rat uterine smooth muscle, but at higher concentrations it had inhibitory effect on rat uterus contraction.