Cervical diameter in relation to uterine and cervical EMG activity in early postpartum dairy cows with retained placentas after PGF2alpha induced calving

The cervix must regain its normal diameter after parturition. Until now, little has been known about the pattern of cervical closure and the possible influences of myometrial and cervical contractions in this process. We continuously measured the cervical diameter with ultrasound cervimetry during the first 48h after calving in six cows with retained fetal membranes, while uterine (n=6) and cervical outer muscular layer (n=4) electromyographic (EMG) activity was measured with bipolar EMG electrodes. We found that the cervical diameter which was 6.2cm (+/-0.7) at 1.4h after calving, initially increased to 9.0cm (+/-1.0) during the first 14.8h (+/-2.8) postpartum. After this time, the diameter decreased gradually to 5.3cm (+/-1.0) at 48h after calving. The overall EMG activity after parturition decreased by 59% (+/-6) and 35% (+/-17) for the uterus and cervix, respectively. The decrease in EMG activity was due to a 50% (+/-7) decrease in EMG amplitudes of the myometrium; the EMG amplitudes of the cervix decreased by only 8% (+/-21) (P>0.05). At the same time in the cervix, burst frequency decreased by 69% (+/-17), while the decrease in burst frequency of the myometrium was only 11% (+/-5) (P>0.05). Uterine myometrial and cervical EMG activity after parturition showed burst patterns. These contractions of the uterus and cervix were accompanied by and correlated with transient dilatations of the caudal cervix. This could have functional relevance in the evacuation of the uterus.     

Cervical dilatation related to uterine electromyographic activity and endocrinological changes during prostaglandin F(2alpha)-induced parturition in cows

The temporal relationship between changes in cervical dilatation, uterine electromyographic (EMG) activity, and maternal plasma concentrations of estradiol 17beta (E(2)), progesterone (P(4)), and 13,14-dihydro-15-keto-prostaglandin-F(2alpha) (PGFM), was investigated in six parturient cows. Calving was induced with a single injection of a synthetic analogue of prostaglandin F(2alpha) (PG) on Day 274 of gestation. Cervical dilatation was measured continuously by measuring the transit time between two implanted ultrasound crystals while at the same time uterine EMG activity was measured through two silver electrodes sutured on the myometrial surface until the expulsive stage of calving had been reached. In blood samples collected at 4-h intervals, starting at the moment of PG injection, the mean plasma E(2) concentration gradually increased and was significantly elevated at 28 h after PG injection. At 4 h after PG treatment, the mean P(4) concentration had dropped significantly and continued to decrease until a value of around 1 ng/ml was reached, where it stayed until the onset of expulsion. Mean plasma PGFM concentrations increased steadily after PG injection, reaching significantly elevated concentrations at 20 h after treatment. In the five cows that delivered calves in anterior positions, uterine EMG activity, expressed as root mean square (RMS in microV), started to increase at a mean interval (+/- SD) of 13.1 +/- 3.7 h following PG treatment. The increase in EMG activity was significantly correlated with changes in plasma PGFM concentrations. In these cows, dilatation of the caudal cervix started after a mean (+/- SD) interval of 28.5 +/- 1.5 h following PG treatment and dilatation progressed at a mean (+/- SD) rate of 2.25 +/- 0.24 cm/h. In one cow with a calf in the posterior position, uterine EMG activity and dilatation started at 15.8 h and 31.8 h, respectively, after induction of calving. We conclude that a predictable sequence of physiological changes occurs around induction of calving, which allows specific timing of future studies on cellular and biochemical changes within the cervix during parturition.     

EMG activity of the muscular and stromal layer of the cervix in relation to EMG activity of the myometrium and cervical dilatation in PGF2alpha induced parturition in the cow

The goal of this study was to quantify and characterize the electromyographic (EMG) activities in the cervical outer muscular layer and in the cervical stromal layer, and to characterize their relationship with myometrial EMG activity and cervical dilatation during PGF2alpha-induced parturition in term pregnant cows. We continuously measured the EMG activity of the uterine myometrium and cervical outer muscular layer as well as the cervical stromal layer in five cows using bipolar electrodes while at the same time measuring changes in the cervical diameter with ultrasound cervimetry. This we did from the moment a prostaglandin analogue was injected until the expulsion of the calf. In contrast to the cervical stromal layer, the cervical outer muscular layer showed distinct EMG activity, which began to increase at about the same time as the EMG activity of the myometrium, i.e. some 12 h before the start of cervical dilatation. However, the rate of this increase was lower than in the myometrium and it was not characterized, like in the myometrium, by an increase in maximum EMG amplitude. Although the cervical outer muscular layer showed contracture and contraction like EMG activity in unison with in the myometrium, it was also characterized by a more irregular EMG activity, which occurred independently from the myometrium. These data suggest that while the outer muscular layer of the cervix may be considered to be a caudal continuation of the myometrium, it also displays activity independently from the myometrium. The physiological relevance of this activity remains to be explored.     

Characteristics of bovine early puerperal uterine contractility recorded under farm conditions

A non-invasive, digital technique was used to measure and quantify intrauterine pressure (IUP) changes in early postpartum dairy cows kept under farm conditions in order to document physiological changes in uterine contractility after uncomplicated calvings. In addition, possible relationships between characteristics of uterine contractility and blood ionized calcium (Ca(2+))-concentrations were investigated. Recordings of uterine contractility were made by using a transcervically inserted open tip catheter in 12 healthy cows during their first 48h after calving. The IUP recording technique appeared easily applicable under farm conditions. Although mean frequency (FREQ), amplitude (AMP) and area under the curve (AUC) of the myometrial contractions significantly decreased due to time, untreated early postpartum cows showed a high variability in characteristics of uterine contractility. There was no correlation between blood Ca2+ -concentrations and any of the contractility parameters.     

Uterine motility in the cow during the estrous cycle. I. Spontaneous activity

This study describes a method for measuring intrauterine pressure (IUP) changes and uterine motility in cows. Spontaneous uterine motility was recorded during the estrous cycle in stanchioned, nonlactating dairy cows using a pair of miniature pressure transducers mounted 15 cm apart at the distal end of a dacron catheter placed in one uterine horn via the cervix. Clinical examination of ovarian status and determination of the peripheral plasma levels of estradiol-17beta and progesterone were used to determine the stages of the cycle. The pressure sensors recorded variations in muscular resting tension (tone) and the occurrence, spatial distribution, and force of the uterine contractions. Both tone and uterine activity varied significantly during the cycle. They were minimal during diestrus, increased during proestrus, reached maximal values at estrus, and then decreased. The highest synchronized motor activity with presence of peristaltic-antiperistaltic movements occurred during estrus. The prevailing direction of the uterine contractions during late estrus (immediate preovulatory period) was cervico-tubal.     

Prostaglandin-induced luteolysis in pregnant and pseudopregnant rabbits and the resultant effects on the myometrial activity.

The effect of prostaglandin (PG)-induced luteolysis on the myometrial activity in 20--21-day-pregnant and 11--12-day-pseudopregnant rabbits was studied by intrauterine pressure (IUP) recording during PG infusions. The same dose of PG (10 micrograms/h during 8h) was also given to 7 non-pregnant (untreated) does that were used as controls. Peripheral plasma concentration of progesterone and oestradiol-17 beta were measured at 2-h intervals during the infusion. Plasma progesterone level decreased significantly within 2 h or the start of infusion in pregnant and pseudopregnant does and continued to decrease; at the end of 8 h, the concentrations were 31 and 41%, respectively, of the pre-infusion levels. The amplitude of uterine contractions increased significantly after 4 h in pseudopregnant does, increased slightly but insignificantly in the pregnant does and showed no significant change in the non-pregnant does during PG infusion. The amplitudes developed in the pregnant and pseudopregnant does were significantly different. The direct effect of progesterone (1--3 micrograms/h during 4 h) was also studied in 7 non-pregnant rabbits. After 2 h the amplitude of contractions had decreased markedly and the pattern of activity had become irregular. The results support the concept of a myometrial inhibitory factor other than progesterone in rabbit pregnancy and suggest that this factor(s) originates in conceptus.     

The efficacy and acceptability of the ″prostaglandin impact″ in inducing complete abortion during the second week after the missed menstrual period

Twenty-two pregnant patients were exposed, 12±1 days after their missed menstrual period, to a single intrauterine dose of 5mg PG F2_α, to provoke a PG ″Impact″ (PGI) and through it legal abortion. The PGI, delivered through the cervix during 10 minutes, induced 83±9mm Hg contracture in 20±3 minutes. Cyclic IUP reached 102±10mm Hg only in 116±14 minutes, it was then sustained for about 2 hours and subsequently declined.During the evolution of IUP uterine bleeding appeared, progesterone (P) and estradiol 17_β (E₂) started to decrease and continued decreasing. At 24 hours after PGI, P-withdrawal was 44% (P<0.05), bleeding continued and cervical dilatation approximated 1cm. Subsequently uterine bleeding (containing tissue fragments) continued and out of 22 women 20 aborted completely. After 3–5 days bleeding declined, the pregnancy tests became negative and normal menstrual periods one month after PGI provided the desired end points of the study. Complete abortions, simulating the symptoms of delayed menstrual periods, had a high Abortion Score of 95 and in the sedated patients the side effects were infrequent, mild and acceptable. This clinical outcome encourages extensive field trials.None of the patients aborted during the short lived period of exogenous PG stimulation. However, the continued steroid withdrawals indicated that PGI damaged the endocrine function of the ovum and the luteotrophic support of the corpus luteum. Therefore, if it was PG which completed abortion eventually, it had to be the endogenous compound, having become effective in physiological concentrations, due to the threshold-lowering action of P-withdrawal.     

The efficacy and acceptability of the "prostaglandin impact" in inducing complete abortion during the second week after the missed menstrual period

Clinical research was undertaken using PGF2a (prostaglandin) to induce abortion in 22 pregnant women at 12 +/- 1 days following their missed menstrual period. The PG was administered in a 5 mg single intrauterine dose through the cervix for a 10-minute period. The PG administration caused increased uterine contraction within 20 minutes and raised intrauterine pressure which was sustained for 2 hours. During the initiation of the intrauterine pressure, bleeding started and progesterone and estradiol levels decreased and continued to do so. In those patients who had been sedated, side effects were minimal. At 24 hours following the PG administration, progesterone had been withdrawn at a rate of 44%, bleeding was continuing, and cervical dilatation was at approximately 1 cm. Complete abortion was achieved in 20 out of the 22 women. It is believed that the abortion was effected through the action of endogenous PG, due to the withdrawal effect on progesterone of the exogenously-administered PG.     

Uterine motility in the cow during the estrous cycle. II. Comparative effects of prostaglandins F(2alpha), E(2), and cloprostenol

Intrauterine pressure (IUP) changes were recorded in nonlactating, cyclic dairy cows using transcervically placed intraluminal pressure microtransducers. Spontaneous activity was recorded for the first 30 min. Prostaglandins (PG) F(2alpha) (5 mug/kg), E(2) (5 mug/kg), or cloprostenol (0.1 mug/kg) were then injected intravenously (i.v.) at diestrus, proestrus, estrus, and metestrus, and their effects were recorded. The drug administrations did not alter the duration of the estrous cycle of the cows. Single doses of PGF(2alpha) and E(2) significantly increased uterine activity at all stages of the estrous cycle, while cloprostenol had no effect. PGF(2alpha) and PGE(2) increased IUP, frequency, and amplitude during all stages of the estrous cycle. The spontaneous pattern resumed within 20 min postinjection. Partial uterine refractoriness occurred with both PGs. The results indicate that low doses of natural prostaglandins stimulate uterine activity during the estrous cycle in cattle.     

Release of proinflammatory cytokines related to luteolysis and the periparturient acute phase response in prostaglandin-induced parturition in cows

An acute phase response was previously found in cows at parturition, which might be associated with uterine cytokine release. Five late pregnant cows were implanted with vascular catheters in both the maternal aorta and uterine vein. Blood samples were taken to study temporal relationships between changing plasma levels of proinflammatory cytokines and the periparturient acute phase response following prostaglandin (PG)-induced luteolysis at Day 275 of gestation. The plasma levels of three proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6), as well as progesterone (P4), PGFM and serum amyloid A (SAA) were measured every 4 h between PG induction and expulsion of the calf. In the arterial plasma, progesterone levels dropped to baseline levels within 10 h following PG treatment, indicative of complete luteolysis. Contrary to expectations, the uterine vein samples showed lower proinflammatory cytokine levels compared with the maternal aorta values. A classical acute phase response, as assessed by SAA, was observed during the expulsive stage, but not during luteolysis.     

Effect of different doses of prostaglandin E2 on intrauterine pressure and uterine motility during diestrus in experimental cows

Studies in human medicine proved the important role of prostaglandin E2, which stimulates uterine contractions in vivo and in vitro and has been extensively used to ripen the cervix around labor. We wanted to demonstrate that increasing the dosage of prostaglandin E2 (1.25 mg, 2.5 mg, 5 mg and 10 mg) provokes an increase in intrauterine pressure and uterine motility in cattle. Five healthy, lactating dairy cows were used as experimental animals for this study. Intrauterine pressure was recorded during the diestrus phase (1 recording per cow and diestrus phase) by means of a transcervically placed intraluminal pressure microtransducer. Physiologic uterine motility was recorded for 30 min, then placebo or one of the prostaglandin E2- dosages was administered through an indwelling catheter in the jugular vein, followed by a 2-h recording period (eight 15-min periods). Area under the curve (AUC), mean amplitude, frequency of pressure waves and intrauterine pressure were analyzed. Furthermore, we recorded protocols for monitoring heart and respiratory rates and side effects at 9 given examination times. Significant differences were found for the AUC, the mean amplitude and the intrauterine pressure (P < or = 0.05), whereas the number of pressure waves per 15 min did not differ significantly among treatments. Peak values for AUC, mean amplitude and intrauterine pressure were found during the first 15 min after administration of 10 mg of prostaglandin E2. Dose-effect curves showed that the 2.5 mg dosage provided the optimal ratio between myometrial stimulation and undesirable side-effects.     

Cardiac output during labour.

Serial measurements of cardiac output and mean arterial pressure were performed in 15 women during the first stage of labour and at one and 24 hours after delivery. Cardiac output was measured by Doppler and cross sectional echocardiography at the pulmonary valve. Basal cardiac output (between uterine contractions) increased from a prelabour mean of 6.99 l/min to 7.88 l/min at greater than or equal to 8 cm of cervical dilatation as a result of an increase in stroke volume. Over the same period basal mean arterial pressure also increased. During uterine contractions there was a further increase in cardiac output as a result of increases in both stroke volume and heart rate. The increment in cardiac output during contractions became progressively greater as labour advanced. At greater than or equal to 8 cm of dilatation cardiac output increased from a basal mean of 7.88 l/min to 10.57 l/min during contractions. There were also further increases in mean blood pressure during contractions. One hour after delivery heart rate and cardiac output had returned to prelabour values, though mean arterial pressure and stroke volume remained raised. By 24 hours after delivery all haemodynamic variables had returned to prelabour values. Haemodynamic changes of the magnitude found in this series are of considerable clinical relevance in managing mothers with complicated cardiovascular function.     

The effects of ovariectomy and strech on the regulatory profile and activity of the uterus

Following ovariectomy of five New Zealand white rabbits at day 25 of pregnancy, the intrauterine pressure (IUP) and uterine progesterone (P) and prostaglandin (PG) levels were measured sequentially at days 25, 26 and 27. At day 25, when the uterine P and PGE and PGF were high, massive intrauterine treatment with 500 μg PGF2α provoked only a sustained contracture on which only low level oscillation in IUP was superimposed. At day 26, when the P levels had decreased significantly (P<0.001) and the PG levels had not changed significantly, 50 μg PGF2α significantly increased cyclic IUP as compared with the day 25 value (P<0.001). At day 27, when the P levels decreased further, as little as 5 μg PGF2α provoked still higher cyclic IUP, in spite of a significant reduction in PG levels (P<0.05).Stretching the uterus of six post partum and six 26 days pregnant rabbits (after removing the uterine contents) significantly increased the uterine PGF levels (P<0.001). However, stretch increased only cyclic IUP of the post partum uterus and was without effect on the pregnant uterus, which still had high P levels. These results indicate that the myometrium activated by exogenous PG or stretch, regardless of whether the uterine PG levels increase, remain unchanged or even moderately decrease, provided that the uterine P levels are reduced to a critical value.     

Relation between fetal arterial PO2 and oxytocin-induced uterine contractions in pregnant sheep

The relation between oxytocin-induced type A uterine contractions and fetal arterial PO2, measured continuously with an intravascular oxygen electrode, was studied in nine chronically catheterized sheep during late pregnancy. Oxytocin provoked dose-related increases in intrauterine pressure (IUP) and decreases in fetal PaO2. There was a significant positive relationship between changes in IUP and the maximum decrease in fetal PaO2 (average r = 0.696, df = 92; P less than 0.001). We conclude that changes in uterine activity contribute to transient fetal hypoxemia, and that administration of exogenous oxytocin provides an experimental paradigm to examine the consequences of this relationship.     

Postpartum suppression of ovarian activity with a Deslorelin implant enhanced uterine involution in lactating dairy cows

Holstein cows received, subcutaneously a non-degradable implant containing 5mg of the GnRH agonist Deslorelin (DESL) or no implant (CON) at 2+/-1 days postpartum (dpp). All cows were injected with PGF(2alpha) at 9 dpp. Previous pregnant (PPH) and non-pregnant uterine horns (PNPH) were determined by palpation per rectum. In Experiment 1, cows [DESL implant (n=10) and CON (n=9)] were examined by ultrasonography to record ovarian structures (23, 30 and 37 dpp) and uterine horn and cervical diameters (16, 23, 30 and 37 dpp). Uterine tone was scored before ultrasonography. Vaginoscopy was conducted just after ultrasonography examination to assess cervical discharge and color of the external cervical os. Blood samples were collected on a weekly basis for hormonal analyses. In Experiment 2, cows [DESL implant (n=77) and CON (n=70)] were palpated per rectum and vaginoscopy at 30 dpp for scoring of uterine tone, uterine horns, cervical diameter, and discharge. Blood samples were collected only at 9 dpp. In Experiment 1, DESL-implant-treated cows had more Class 1 follicles (P<0.01), less Class 2 (P<0.01) and Class 3 follicles (P<0.01) and no corpus luteum (CL) formation (P<0.01). In CON cows, six of nine animals had visible CL at 25+/-7 dpp. At 9 dpp plasma concentration of E(2), P(4) (P<0.01) and PGFM (P<0.05) were less in the DESL-implant treatment group. Diameter of PPH (P<0.01), PNPH (P<0.01) and cervix (P=0.08) were less in the DESL-implant treatment associated with greater uterine tone (P=0.07). The DESL-implant cows had a greater frequency of clear cervical discharge (P=0.09) and pink cervical os (P=0.06). In Experiment 2, plasma concentrations of PGFM were less at 9 dpp in DESL-implant treatment (P<0.01). Diameters of the PPH (P<0.01) and PNPH (P<0.01) were less and more uterine tone (P<0.01) in the DESL-implant treatment. Diameter of cervix and frequency of a cervical discharge score did not differ between treatments. Treatment with non-degradable Deslorelin (5mg) implant during postpartum: (1) suppressed ovarian follicular development, (2) enhanced physical involution of the uterus and cervix, (3) increased tone of the uterine wall, (4) decreased frequency of purulent cervical discharges, and (5) reduced inflammatory processes of the reproductive tract.     

Letter: On the administration of prostaglandins as a pre-operative means of cervical dilatation

Prostaglandin (PG) administration by the intramuscular or extraamniotic route has been reported to be a safe and reliable means of effecting cervical dilatation prior to 1st trimester abortion by suction curettage. At the Mulago Hospital, Kampala, a minimum of 5 cases of 1st trimester abortions were performed weekly using the Karman cannula (KC), a flexible polyethylene catheter which lessens the risk of cervical dilatation. In none of the cases was cervical dilatation required for insertion of a KC of sufficient diameter. Paracervical block with procaine 2% (10 ml) was used for analgesia; in rare cases, 10 mg of diazepan was administered orally or intravenously as a preoperative medication. Complications encountered included: 1) perforation of the uterine fundus; 2) metritis; and 3) retained products of conception. With proper instrumentation, cervical dilatation is no longer required for 1st trimester abortions. PG administered for cervical dilatation is no longer justified because it is time consuming, a source of additional expense, inconvenient, and is associated with uterine cramps and gastrointestinal side effects. In occasional cases, as in undue cervical resistance, the use of PGs may be justified.     

Concentrations of spermatozoa in the vagina of heifers after deposition of semen in the uterine horns, uterine body or cervix

In Exp. I, virgin Holstein heifers (N = 18) were induced into oestrus with PGF-2 alpha. Animals which stood to be mounted were paired for insemination approximately 8 h later with 56.1 x 10(6) spermatozoa from a single bull. Semen was deposited in the uterine body of one female. Each matched female was inseminated by deposition of one-half of the inseminate into the right uterine horn and one-half into the left uterine horn approximately 7.0 cm anterior to the internal cervical os. In Exp. II, additional heifers (N = 18) were induced into oestrus and inseminated by deposition into the uterine horns or cervix (2.0 cm anterior to the external cervical os). A 1.0 ml aspirate of vaginal mucus was collected at hourly intervals for 8 h after insemination. Concentration of spermatozoa was determined by haemocytometry. In Exp. I, cumulative percentage spermatozoa recovered in an 8 h collection period were similar (P greater than 0.10) for insemination into the uterine horns (17.9 +/- 2.9%) and uterine body (18.5 +/- 4.5%). In Exp. II, cumulative % sperm recovery from the vagina was greater (P less than 0.10) for cervical deposition (59.1 +/- 14.1%) than for that into the uterine horns (30.9 +/- 7.8%). In Exp. II, the insemination treatment x hour of sample interaction was significant (P less than 0.08). Recovery of spermatozoa from the vagina was greatest (P less than 0.05) within 3 h after cervical insemination (31.4 +/- 9.9% compared to 9.4 +/- 2.5% for uterine horn deposition). Percentage recovery of spermatozoa from the remaining hourly collections were similar (P greater than 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of prostaglandin E2, DL-cloprostenol,and prostaglandin E2 in combination with D-cloprostenol on uterine motility during diestrus in experimental cows

Prostaglandin F(2alpha) is used in dairy herd management because of its luteolytic properties and for its direct effect on the myometrium in cows diagnosed with endometritis. Prostaglandin E(2) has a contractile effect on the bovine uterus. In human medicine, prostaglandin E(2) is routinely used to maintain labor and to ripen the cervix. We hypothesized, that a combination of prostaglandin F(2alpha) and prostaglandin E(2) would provoke a long-lasting increase in intrauterine pressure (IUP) and uterine motility as compared to either prostaglandin group. Intrauterine pressure was recorded during the diestrus of eight lactating dairy cows using a transcervically placed intraluminal pressure microtransducer. After recording of physiologic uterine motility for 30min, prostaglandins (DL-cloprostenol, PGE(2), PGE(2) in combination with D-cloprostenol) or placebo were administered, followed by a 2h recording period. Significant differences were found for the area under the curve, the mean amplitude and the intrauterine pressure, whereas the number of pressure waves did not differ significantly among treatments. Peak values for area under the curve and mean amplitude were found during the first 15min for the combination of PGE(2) and D-cloprostenol. During the last 15min of the recording session, area under the curve and mean amplitude were increased only for the combination of PGE(2) and D-cloprostenol as compared to placebo. Although PGF(2alpha) and PGE(2) provoke an increase in intrauterine pressure, only their combination guarantees a significant effect over a 2h recording period.     

Anti-inflammatory effect of proteoglycan and progesterone on human uterine cervical fibroblasts

AimsThe aim of this study was to compare the anti-inflammatory effect of proteoglycan (PG) with that of progesterone (P) in the cultured fibroblasts from human uterine cervix.Main methodsAfter obtaining informed consent, the cervix was collected from normal women undergoing total hysterectomy. The cervix was cultured until fibroblasts proliferated and had grown to confluence, then, the fibroblasts were stimulated by lipopolysaccharide (LPS) with or without PG, P and a combination of both; they were cultured for 24–48 h. The anti-inflammatory effects of PG and P were evaluated by the suppression of IL-6 or IL-8 secretion. The expression of the IL-6 or IL-8 gene and the expression of their protein were determined by real-time PCR, and ELISA, respectively. Activation of Toll-like receptor (TLR) 4 was evaluated by Western blotting.Key findingsLPS markedly enhanced gene and protein expression of IL-6 and IL-8 in human uterine cervical fibroblasts. The up-regulation of the IL-6 or IL-8 gene and protein expression by LPS was significantly suppressed with PG, P and a combination of both. Western blotting revealed that combination of PG and P showed more potent inhibition on LPS-stimulated TLR4 induction than that seen by each.SignificanceThis study showed that both PG and P have an inhibitory effect on LPS-induced inflammation. This anti-inflammatory effect of PG and P was augmented by co-administration of both, suggesting for the first time that PG has an anti-inflammatory effect on human uterine cervical fibroblasts.     

Dehydroepiandrosterone sulfate stimulates collagenase synthesis without affecting the rates of collagen and noncollagen protein syntheses by rabbit uterine cervical fibroblasts

The effects of dehydroepiandrosterone 3-sulfate (DHAS) and 17 beta-estradiol (E2) on collagen and noncollagen protein syntheses by rabbit uterine cervical cells were studied, and their effects on latent collagenase synthesis were compared. DHAS (1 X 10(-6) M) stimulated the synthesis of latent collagenase and did not affect the cell number and [3H]thymidine incorporation into DNA, whereas E2 had no effect on collagenase synthesis. On the other hand, neither DHAS (1 X 10(-6) M) nor E2 (1 X 10(-10)-1 X 10(-6) M) showed effects on collagen and noncollagen protein syntheses. These results suggest that the stimulative effect of DHAS on cervical ripening is mediated mainly by the stimulation of collagen catabolism, and that E2 does not concern the changes in the concentration of collagen and noncollagen protein in uterine cervix of the rabbit during pregnancy at term.