scholarly journals Effect of the oestrous cycle, pregnancy and uterine region on the responsiveness of the isolated mouse uterus to prostaglandin F2α and the thromboxane mimetic U46619

2006 ◽  
Vol 188 (3) ◽  
pp. 569-577 ◽  
Author(s):  
A L Griffiths ◽  
K M Marshall ◽  
J Senior ◽  
C Fleming ◽  
D F Woodward

Previous studies in this laboratory have suggested that the isolated uterus from non-pregnant mice has a prostaglandin F and a thromboxane receptor population similar to that found in human myometrium. The aim of this study was to investigate any regional variation in myogenic activity ) and the and responsiveness to prostaglandin F2α (PGF2α thromboxane mimetic U46619 in the mouse uterus taken during different stages of the oestrous cycle and during pregnancy. Uterine samples from BKW mice were taken from different anatomical segments along the length of each uterine horn and set up for superfusion at 2 ml/min with Krebs solution (containing 1 μM indometacin) at 37 °C, and gassed with 95%O2/5%CO2. Responses (area under the curve) are expressed as a percentage of the final contraction induced by hypotonic shock. Data are expressed as the means ± s.e.m. of n=5–12 and were analysed using Student’s paired t-test or two-way ANOVA with a Bonferroni post hoc test. Regional variation in myogenic activity was observed in all tissues studied except those taken during labour. These tissues displayed significantly greater myogenic activity than tissues taken at late gestation and at all stages of the oestrous cycle. Tissues from pregnant animals were generally more responsive to U46619 and PGF2α than tissues taken from non-pregnant animals. Tissues taken from the upper segment of the uterine horn were more responsive to both agonists during the oestrous cycle. The findings demonstrated that the hormonal milieu and site of excision are important for myogenic activity and responsiveness.

2008 ◽  
Vol 197 (1) ◽  
pp. 171-179 ◽  
Author(s):  
Deborah P Fischer ◽  
Jonathon A Hutchinson ◽  
Diane Farrar ◽  
Peter J O'Donovan ◽  
David F Woodward ◽  
...  

Prostaglandins (PG) E2, PGF2α and thromboxane (TX) mediate uterine contractility by targeting prostonoid EP, FP and TP receptors respectively. The aim of this study was to elucidate the function of these receptors in isolated human myometrium taken at term gestation prior to and following labour onset. Lower segment myometrial strips were immersed in organ baths in oxygenated Krebs' solution at 37 °C and connected to isometric force transducers. After equilibration, spontaneous activity and concentration responses to PGE2, PGF2α and U46619 (a stable TX mimetic) were measured as area under the curve and expressed as a percentage of the final contraction induced by hypotonic shock. Results were expressed as arithmetic means±s.e.m. and analysed using two-way ANOVA with Bonferroni's post hoc test. Myometrium excised at late gestation displayed the greatest spontaneous activity compared with the tissues taken during labour (P<0.001). Excitation evoked by PGF2α (P<0.01) and PGE2 at 10−5 mol/l were attenuated after labour onset. U46619 consistently stimulated concentration-dependent contractions (P<0.001) and selective antagonists confirmed TP-mediated effects. The maintained responses to TX indicate crucial roles for TP receptors in the muscular tonus of the parturient uterus. This receptor and its secondary messenger system represent effective myometrial targets for tocolytic agents in both pregnancy and labour-associated disorders.


1976 ◽  
Vol 68 (3) ◽  
pp. 445-451 ◽  
Author(s):  
F. R. BLATCHLEY ◽  
B. T. DONOVAN ◽  
N. L. POYSER

SUMMARY The presence of beads in the guinea-pig uterus caused premature regression of the corpora lutea, and a corresponding decrease in utero-ovarian venous plasma levels of progesterone, by days 9–10 of the oestrous cycle. If the beads were placed in one horn only, premature luteal regression occurred only in the adjacent ovary. Induced luteal regression was preceded by an increased release of prostaglandin F2α (PGF2α) from the uterine horns which contained the beads. Oestradiol benzoate treatment of guinea-pigs carrying beads in one uterine horn overcame the unilateral effect and resulted in premature luteal regression in both ovaries. This was also associated with the early release of PGF2α from both uterine horns, though a difference in the timing of the release was apparent between the bead-containing (experimental) and control horns.


2009 ◽  
Vol 21 (5) ◽  
pp. 709 ◽  
Author(s):  
Marta Wasielak ◽  
Katarzyna Kamińska ◽  
Marek Bogacki

The present study was conducted to evaluate the effect of the conceptus on uterine prostaglandin-F2α (PGF2α) and prostaglandin-E2 (PGE2) release and the expression of prostaglandin synthase enzymes during the periimplantation period in the pig. A surgically generated model with conceptuses developing in only one of the uterine horns was created. The highest concentration of PGF2α and PGE2 was found in the gravid uterine horn, compared with the non-gravid horn and the intact horn of cyclic gilts. Endometrial concentration of both PGs in pregnant gilts was elevated regardless of the conceptus in the uterine horn, whereas only myometrial PGE2 concentration increased during pregnancy. Expression of prostaglandin-E2 synthase (mPGES-1) mRNA in the endometrium was upregulated during the oestrous cycle, while protein expression presented a similar pattern to that of PGE2 concentration in the uterine flushings. Prostaglandin-F2α synthase (PGFS) mRNA and protein expression in the endometrium did not differ between pregnancy and oestrous cycle but PGFS mRNA in the myometrium increased during pregnancy both in the gravid and the non-gravid uterine horns. We suggest a local effect of the conceptus on PG release pathways but also a more systemic effect within the whole uterus with regard to PG synthesis and accumulation in uterine tissues.


2011 ◽  
Vol 23 (6) ◽  
pp. 798 ◽  
Author(s):  
Hyun Jung Park ◽  
In Sun Kuk ◽  
Jin Hoi Kim ◽  
Jae Hwan Kim ◽  
Sang Jin Song ◽  
...  

During the oestrous cycle, pregnancy and parturition, the uterus undergoes marked morphological, physiological and functional changes. Amid these changes, the Wnt/β-catenin signalling pathway has been identified as having a crucial role in regulating associated biological events. Recently, based on results from a mouse embryo study, interferon-induced transmembrane protein 1 (Ifitm1) was reported as a downstream molecule of the Wnt/β-catenin signalling pathway. Differential expression patterns of the Ifitm1 gene during the oestrous cycle, pregnancy and parturition were identified in the present study. Quantitative real-time polymerase chain reaction data from uterine samples of mice induced start the oestrous cycle by injection of human chorionic gonadotropin (hCG) and revealed that Ifitm1 mRNA expression increased from late pro-oestrus to metoestrus, and decreased during dioestrus and early pro-oestrus. During pregnancy, Ifitm1 gene expression was minimal until parturition, but increased markedly 2 days after parturition. This significant elevation in Ifitm1 gene expression at post partum stage was identical to Ifitm1 expression after the induction of abortion by injection of prostaglandin F2α. Interestingly, pregnant mare serum gonadotropin (PMSG) and oestrogen are also facilitates changes in Ifitm1 gene expression in an ovariectomised (OVX) mouse model. Expression of Ifitm1 mRNA was higher in response to PMSG than other hormones investigated. These results suggest that Ifitm1 may be involved in uteri physiology, although the mechanisms involved in the regulation of this gene expression and function in the uterus remain unknown. In the present study, differential expression patterns of the Ifitm1 gene were identified in the uteri of mice and the correlation between the patterns of Ifitm1 gene expression and Wnt/β-catenin signalling discussed.


1993 ◽  
Vol 120 (1) ◽  
pp. 103-106 ◽  
Author(s):  
E. R. Mutiga ◽  
E. Mukasa-Mugerwa ◽  
T. Azage

SUMMARYThe luteolytic effect of prostaglandin F2α (PGF2α) during the confirmed luteal phase of the oestrous cycle was evaluated in ten Boran and ten Boran × Friesian cross-bred heifers. Following injection with 25 mg Lutalyse, animals were bled every 6 h for 96 h and plasma progesterone (P4) determined by the ELISA technique. Borans had significantly (P < 0·05) smaller corpora lutea (12·01±0·72 ν. 17·03±2·10 mm) and responded faster to PGF2α injection (65·57±1·40 ν. 78·27±2·18 h) than the cross-bred heifers. However, there was no significant difference in either the initial P4 values (6.24±0·98 ν. 8·00±1·71 ng/ml) or the rate of its decline following PGF2α injection between the two breeds. Values declined sharply to basal levels (11% of the initial pretreatment values) within 48 h in both breeds. All ten cross-breds and eight Borans showed standing oestrus within a week of treatment. However, oestrus was better synchronized (P < 0·05) in Borans than cross-breds. It was concluded that PGF2α is effective for oestrus synchronization in both breeds, but oestrus occurred earlier and was more precise in Borans than in cross-breds.


1999 ◽  
Vol 47 (2) ◽  
pp. 249-262 ◽  
Author(s):  
Genowefa Kotwica ◽  
Anita Franczak ◽  
S. Okrasa ◽  
J. Kotwica

The role of oxytocin (OT) in the regulation of prostaglandin F2α (PGF2α ) secretion during luteolysis in gilts was studied using a highly specific OT antagonist (CAP-581). In Experiment 1 gilts on Days 14 to 19 of the oestrous cycle in Latin square design were used, to determine the dose and time of application of OT and CAP. In Group I (n = 6) gilts were treated intravenously with saline or with 10, 20 and 30 IU of OT. Concentrations of the main PGF2α metabolite i.e. 13,14-dihydro-15-keto-prosta-glandin F2α (PGFM) were measured in blood samples as uterine response to the treatment. Twenty IU of OT was the most effective to stimulate PGFM release and this dose was used after CAP treatment in gilts of Groups II, III and IV. Gilts of Group II (n = 3) were injected into the uterine horns (UH) with saline (5 ml/horn) or CAP (2 mg, 3 mg and 4 mg; half dose/horn) and OT was injected (i.v.) 30 min thereafter. Any of the CAP doses given into the UH affected PGFM plasma concentrations stimulated by OT. In Group III (n = 4) gilts were infused (i.v.) for 30 min with CAP (9 mg, 14 mg and 18 mg/gilt) followed by 20 IU of OT. All doses of CAP effectively inhibited OT-stimulated PGF2α release, therefore 9 mg was selected for the further studies. Gilts of Group IV (n = 4) received OT 4, 6 and 8 h after CAP to define how long CAP blocks the OT receptors. Concentrations of PGFM increased after any of this period of time. Thus, we concluded that 9 mg of CAP infused every 4 h will effectively block OT receptors. In Experiment 2, gilts (n = 4) received CAP as a 30-min infusion every 4 h on Days 12-20 of the oestrous cycle. Control gilts (n = 3) were infused with saline. CAP infusions diminished the height of PGFM peaks (P < 0.05). Frequency of the PGFM (P < 0.057) and OT (P < 0.082) peaks only tended to be lower in the CAP-treated gilts. Peripheral plasma concentrations of progesterone (P4) and oestradiol-17β (E2) and the time of luteolysis initiation as measured by the decrease of P4 concentration were the same in CAP-and saline-treated gilts. The macroscopic studies of the ovaries in gilts revealed lack of differences between groups. We conclude that OT is involved in the secretion of luteolytic PGF2α peaks but its role is limited to controlling their height and frequency. Blocking of OT receptors did not prevent luteolysis in sows.


Cephalalgia ◽  
2011 ◽  
Vol 31 (15) ◽  
pp. 1532-1541 ◽  
Author(s):  
Maria Antonova ◽  
Troels Wienecke ◽  
Jes Olesen ◽  
Messoud Ashina

Background: During two decades of migraine provocation studies with naturally occurring signalling molecules, vasodilators such as prostaglandin E2, prostaglandin I2 (prostacyclin) and prostaglandin D2 were shown to be able to induce headache in man. To elucidate the role of inflammation and vasodilatation in the generation of headache, we investigated whether the pro-inflammatory and vasoconstricting prostanoid prostaglandin F2α (PGF2α) would cause headache in a human model of headache. Methods: Twelve healthy volunteers were randomly allocated to receive 3.5 µg/kg/min PGF2α or placebo over 20 min in a two-way crossover study. We recorded headache intensity on a verbal rating scale, middle cerebral artery blood flow velocity (VMCA) and the diameters of the superficial temporal artery (STA) and radial artery (RA). Results: We found no difference in the area under the curve (AUC) for immediate headache (0–90 min) between PGF2α and placebo ( p = 0.144). The McNemar's test showed no difference in the incidence of immediate and delayed headache between verum and placebo ( p = 0.500 and p = 1.000, respectively). There was no difference in VMCA ( p = 0.776) and in the diameter of the STA ( p = 0.460) or RA ( p = 0.780) between PGF2α and placebo. Conclusion: The present study shows that PGF2α, unlike vasodilating prostaglandins, does not provoke headache. We suggest that the vasodilating abilities of prostaglandins are important for the induction of experimental headache in healthy volunteers.


2004 ◽  
Vol 82 (6) ◽  
pp. 363-371 ◽  
Author(s):  
R M Narayansingh ◽  
M Senchyna ◽  
M M Vijayan ◽  
J C Carlson

In this study we examined the mechanism of corpus luteum (CL) regression by measuring changes in expression of prostaglandin G/H synthase-1 (PGHS-1) and -2 (PGHS-2) in day 4 CL and inducible heat shock protein 70 (HSP-70) in day 4 and day 9 CL of immature superovulated rats. The rats were superovulated and treated with 500 µg of prostaglandin F2α (PGF2α) on day 4 or day 9 after CL formation. Ovaries and serial blood samples were removed during the 24-hour period following treatment. Plasma progesterone was determined by radioimmunoassay while mRNA abundance and protein expression were assessed by semiquantitative RT-PCR and immunoblot analysis, respectively. One hour after PGF2α, both day 4 and day 9 rats exhibited a significant decrease in progesterone secretion; however, there was a greater decrease in day 9 rats. In ovarian samples removed on day 4, there was a significant increase in mRNA for PGHS-2 at 1 hour after PGF2α. PGHS-1 mRNA content remained unchanged. Immunoblot analyses showed an increase in PGHS-2 protein expression only at 8 h. There were no changes in PGHS-1 protein expression. In day 9 rats, ovarian HSP-70 protein levels increased by 50% after PGF2α injection; however, on day 4 there was no change in expression of this protein over the sampling period. These results suggest that expression of PGHS-2 may be involved in inhibiting progesterone production and that expression of HSP-70 may be required for complete CL regression in the rat.Key words: rat, prostaglandin F2α, corpus luteum, prostaglandin G/H synthase, heat shock protein-70.


1986 ◽  
Vol 66 (3) ◽  
pp. 643-651 ◽  
Author(s):  
J. A. FITZGERALD ◽  
G. A. EVERETT ◽  
J. APGAR

The effect of low dietary Zn intake upon several plasma endocrine and metabolic profiles was examined during late gestation in the ewe. Thirty adult, primiparous Finncross ewes were fed a low Zn diet with (+Zn, n = 14) or without (0Zn, n = 16) supplemental Zn in the drinking water starting day 1 of pregnancy. Although the mean prepartum progesterone and prolactin concentrations were lower (P < 0.05 and P < 0.01, respectively) in 0Zn than in +Zn ewes, the peak prolactin concentrations in 0Zn ewes at lambing were similar to +Zn ewes. Both basal and thyrotropin-releasing-hormone (TRH)-induced prolactin release were less (P < 0.01) in 0Zn ewes 2 d postpartum. Plasma concentrations of 13, 14-dihydro-15-keto prostaglandin F2α (PGFM) of ewes sampled within 45 min post-lambing were lower (P < 0.05) in 0Zn ewes. There was no difference in cortisol concentrations within 45 min after lambing between 0Zn and + Zn ewes. Plasma protein concentrations in 0Zn ewes were higher (P < 0.01) than those in +Zn ewes during pregnancy. In summary, these data show that low Zn intake in the pregnant ewe affected several endocrine and metabolic plasma parameters associated with normal pregnancy and parturition. Key words: Zinc, parturition, dystocia, feed intake, ovine


Author(s):  
Mark H. Oliver ◽  
Frank H. Bloomfield ◽  
Amita Bansal ◽  
Hui Hui Phua ◽  
Eric B. Thorstensen ◽  
...  

Abstract Maternal periconceptional undernutrition (PCUN) affected fetal pancreatic maturation in late gestation lambs and impaired glucose tolerance in 10-month-old sheep. To examine the importance of the timing of maternal undernutrition around conception, a further cohort was born to PCUN ewes [undernourished for 61 d before conception (PreC), 30 d after conception (PostC), or 61 d before until 30 d after conception (PrePostC)], or normally fed ewes (Control) (n = 15–20/group). We compared glucose tolerance, insulin secretion, and sensitivity at 36 months of age. We also examined protein expression of insulin signalling proteins in muscle from these animals and in muscle from a fetal cohort (132 d of gestation; n = 7–10/group). Adult PostC and PrePostC sheep had higher glucose area under the curve than Controls (P = 0.07 and P = 0.02, respectively), whereas PreC sheep were similar to Controls (P = 0.97). PostC and PrePostC had reduced first-phase insulin secretion compared with Control (P = 0.03 and P = 0.02, respectively). PreC was similar to Control (P = 0.12). Skeletal muscle SLC2A4 protein expression in PostC and PrePostC was increased 19%–58% in fetuses (P = 0.004), but decreased 39%–43% in adult sheep (P = 0.003) compared with Controls. Consistent with this, protein kinase C zeta (PKCζ) protein expression tended to be increased in fetal (P = 0.09) and reduced in adult (P = 0.07) offspring of all PCUN ewes compared with Controls. Maternal PCUN alters several aspects of offspring glucose homeostasis into adulthood. These findings suggest that maternal periconceptional nutrition has a lasting impact on metabolic homeostasis of the offspring.


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