Biomedical subjects

M Brännström

Publications and source records attributed to M Brännström.

At least 19 recordsLinked to original sources

PubMed2006

Gelatinases and their tissue inhibitors during human ovulation: increased expression of tissue inhibitor of matrix metalloproteinase-1.

Remodelling of the extracellular matrix (ECM) of the follicular wall by matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) has been suggested to be crucial in ovulation. To investigate the expression of the gelatinases, MMP-2 and MMP-9, together with their inhibitors, TIMP-2 and TIMP-1, in the perifollicular ovarian stroma from women just before and during ovulation, we obtained biopsies of the stroma adjacent to the leading follicle. Laparoscopic surgery was performed either before the LH peak or at any of three intervals after ovulation triggering by hCG. Immunoblotting, immunohistochemistry and quantitative RT-PCR were performed. All four proteins were expressed by immunoblots, with no detectable changes in the expression of MMP-2, MMP-9 and TIMP-2. Scattered immunostaining for MMP-9 and TIMP-2 was seen, and MMP-2 was demonstrated in a concentric layer. A significant increase in TIMP-1 protein and mRNA was seen during the three ovulatory phases, and a strong and patchy immunostaining for TIMP-1 was shown. This is the first study that has demonstrated an ovulation-associated expression of these ECM-remodelling enzymes around the human follicle at ovulation. The increased expression of TIMP-1 may reflect a specific temporal inhibition of collagenolysis and thereby a time-dependent regulation of ECM breakdown in areas surrounding the apex of the follicle.

Adult↗

PubMed2006

Rejection of the transplanted uterus is suppressed by cyclosporine A in a semi-allogeneic mouse model.

BACKGROUND: A mouse uterus transplantation model has previously been developed for studies of various aspects of uterine transplantation, which in the future may be used as treatment for uterine infertility. The aim of the study was to evaluate the effect of the immunosuppressant cyclosporine A (CyA) on the rejection of the allotransplanted uterus in the mouse. METHODS: C57BL/6 mice were recipients of uteri from F1 hybrids (C57BL/6 x CBA/ca). Transplanted mice received vehicle (control, n=5), 10 or 20 mg/kg/day of CyA (CyA10, n=5 and CyA20, n=5). Untreated F1 hybrids with syngeneic transplants (n=3) were negative controls. On day 10 post-transplantation, the grafted uteri were examined, and biopsies were taken for histology and quantification of T cells. RESULTS: Histology analysis revealed necrosis of the uterine transplants in controls and to a lesser extent in the CyA groups. Apoptosis and inflammation was prominent in grafts from the CyA10 group but suppressed in the CyA20 group. A similar increase of CD4+ cells was seen in all groups, whereas the number of CD8+ cells was higher (P < 0.05) in the two allogeneic groups receiving CyA compared with the allogeneic vehicle group. CONCLUSIONS: CyA treatment clearly delays the progress of rejection of grafted uteri but is insufficient to suppress T cell infiltration. Interestingly, the number of CD8+ cells was higher in groups receiving CyA, possibly reflecting a CyA-dependent depression of activation-induced cell death (AICD) of cytotoxic T cells.

Animals↗

PubMed2005

Rejection patterns in allogeneic uterus transplantation in the mouse.

BACKGROUND: Transplantation of the uterus in the mouse has been developed as a model system for research towards human uterine transplantation. Previous studies in a mouse model have demonstrated that a syngeneic uterus transplant can give rise to normal offspring. The aim of this study was to characterize the time course of rejection in a fully allogeneic mouse uterus transplantation model. METHODS: Uteri of BALB/c mice were transplanted to a heterotopic position in C57BL/6 recipients, whose native uteri were left in situ. The blood flow of the uteri, their gross appearance and general histology and the density of T-lymphocytes were examined on postoperative days 2-28. RESULTS: Macroscopic signs of rejection were apparent from day 5. At the light microscopy level, minimal inflammatory changes were seen from day 5 and massive inflammation was seen from day 10 to day 15. At day 28, necrosis and fibrosis were seen. The density of T-lymphocytes (CD3(+)) was increased in the grafted uterus from day 2 in the myometrium and from day 5 in the endometrium. Blood flow in the grafted uteri was reduced from day 15. CONCLUSION: A murine model to study rejection of allogeneic uterus transplants was characterized. Signs of rejection were seen from day 2 to day 5 and severe rejection was seen from day 10 to day 15. The data will be useful in future studies on immunosuppressants in this model.

Animals↗

PubMed2005

Short-term ischaemic storage of human uterine myometrium--basic studies towards uterine transplantation.

BACKGROUND: Transplantation of the uterus has been suggested as a possible future treatment of absolute uterine infertility. The tolerability of human uterine tissue to cold ischaemic storage was tested in the present study. METHODS: Small tissue samples of human uteri were subjected to cold (4 degrees C) ischaemia (6 and 24 h) in Ringer acetate (RIN), the intracellular-like University of Wisconsin solution (UW) or the extracellular-like Perfadex solution (PER). The ability of myometrial strips to contract, histology by light and electron microscopy as well as tissue concentrations of glutathione, ATP and protein were used as parameters to detect cold ischaemic injuries. RESULTS: Contractile ability and response to prostaglandin F(2alpha) (PGF(2alpha)) was better preserved after 6 h cold ischaemia in UW and PER in comparison with the other groups. Histological examination did not reveal any major changes after 6 and 24 h cold ischaemic storage in UW and PER solutions, while specimens stored in RIN for 24 h displayed degenerative changes on the electron microscopy level. UW and PER preserved ATP concentrations significantly better than RIN. Myometrium stored in UW contained more total glutathione but also a larger proportion of oxidized glutathione than specimens stored in RIN and PER. Protein concentrations did not change with storage time in any of the solutions. CONCLUSIONS: The results show that human uterine myometrial tissue is resistant towards cold ischaemia for at least 6 h if stored in UW and PER solutions.

Adenosine↗

PubMed2005

Safety and efficacy of atorvastatin in patients with severe renal dysfunction.

OBJECTIVE: To investigate the efficacy and safety of a daily dose of 10 mg of atorvastatin in patients with chronic kidney disease (CKD) stages 4 and 5 and a glomerular filtration rate of <30 ml/min. MATERIAL AND METHODS: This was an open, prospective, randomized study. A total of 143 patients were included: 73 were controls and 70 were prescribed 10 mg/day of atorvastatin. As efficacy variables, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels were determined at the start of the study and at 1, 3, 6, 12, 18, 24, 30 and 36 months. RESULTS: The follow-up period was a mean of 20+/-14.4 months (range 1-36 months) for those on atorvastatin versus 22+/-12.7 months (range 0.5-36 months) for the controls. Compared with baseline values, patients treated with atorvastatin had significantly lower concentrations of total cholesterol at Month 36 (5.8 vs 4.4 mmol/l; -23%; p<0.001), of LDL cholesterol at Month 36 (3.6 vs 2.2 mmol/l; -35%; p<0.001) and of triglycerides at Months 24 (2.5 vs 1.9 mmol/l) and 36 (2.5 vs 1.8 mmol/l). The controls had significantly reduced levels of total cholesterol at Month 36 (p<0.21) and of LDL cholesterol at Months 30 and 36. Compared with the controls, the atorvastatin group had lower levels of total cholesterol and LDL cholesterol at Months 1-30. Fifteen patients (21%) stopped taking their medication as they could not tolerate the side-effects, the most frequent complaints being gastrointestinal discomfort and headache. CONCLUSION: Although the medication caused no severe adverse events, we recommend caution when using atorvastatin for severe CKD patients until further evidence of its safety and efficacy is verified.

Aged↗

PubMed2003

Wnt-signalling pathway in ovarian epithelial tumours: increased expression of beta-catenin and GSK3beta.

Beta-catenin is involved in both cell-cell adhesion and in transcriptional regulation by the Wingless/Wnt signalling pathway. Alterations of components of this pathway have been suggested to play a central role in tumorigenesis. The present study investigated, by immunohistochemistry and immunoblotting, the protein expression and localisation of beta-catenin, adenomatous polyposis coli (APC), glycogen synthase kinase 3beta (GSK3beta) and lymphocyte enhancer factor-1 (Lef-1) in normal human ovaries and in epithelial ovarian tumours in vivo and in vitro. Immortalised human ovarian surface epithelium and ovarian cancer cell cells (OVCAR-3) expressed beta-catenin, APC, GSK3beta and Lef-1. Nuclear staining of beta-catenin and Lef-1 were demonstrated only in OVCAR-3 cells. There were significant increases of beta-catenin and GSK3beta, while APC was reduced in ovarian cancer compared to the normal ovary. Beta-catenin and Lef-1 were coimmunoprecipitated in ovarian tumours, but not in the normal ovary. Nuclear localisation of beta-catenin or Lef-1 could not be demonstrated in the normal ovary or in the ovarian tumours. The absence of nuclear localisation of beta-catenin could be due to an increased binding to the cadherin-alpha-catenin cell adhesion complex. In fact, we have earlier reported an increased expression of E-cadherin in ovarian adenocarcinomas. In summary, this study demonstrates an increase in the expression of components of the Wingless/Wnt pathway in malignant ovarian tumours. The increase suggests a role for this signalling pathway in cell transformation and in tumour progression. However, it remains to be demonstrated whether it is an increased participation of beta-catenin in transcriptional regulation, or in the stabilisation of cellular integrity, or both, that is the crucial event in ovarian tumorigenesis.

Adenocarcinoma↗

PubMed2003

Pregnancy in transplanted mouse uterus after long-term cold ischaemic preservation.

BACKGROUND: The aim of this study was to evaluate the viability of the transplanted murine uterus after cold ischaemic preservation. METHODS: Uteri of mice (6-8 weeks old) were isolated and kept at 4 degrees C in vitro for 24 or 48 h in 0.154 mol/l NaCl or University of Wisconsin (UW) solution. Viability was evaluated by assessment of morphology and contractility in vitro. Furthermore, uteri were transplanted by vascular anastomoses to syngeneic recipients after 24 or 48 h cold ischaemic preservation in UW solution and morphology, blood flow and capacity to implant transferred blastocysts were assessed 2 weeks later. RESULTS: Uteri that had been preserved for 24 h exhibited normal morphology but after 48 h preservation minimal degenerative changes were seen. Spontaneous contractions occurred in uteri after 24 h as well as 48 h cold ischaemic preservation and prostaglandin F(2alpha)-stimulated responses were preserved. Blood flow and morphology were normal 2 weeks after transplantation in uteri preserved for 24 h, while grafts preserved for 48 h had a decreased blood flow and morphology showed total necrosis of the transplants. Transplanted uteri that had been preserved for 24 h developed pregnancies (in five out of six animals) after embryo transfer, with offspring showing normal weight and growth trajectory. CONCLUSIONS: This study shows for the first time that the mouse uterus tolerates cold ischaemic preservation and that pregnancies can be carried in transplanted uteri that have been preserved for 24 h.

Animals↗

PubMed2003

Role of the angiotensin II system in regulation of ovulation and blood flow in the rat ovary.

The aim of the present study was to examine the roles of the angiotensin II receptor subtypes, AT(1) and AT(2), in ovulation, and to evaluate the contribution of angiotensin II-mediated pathways in regulation of ovarian blood flow. The AT(1)-specific antagonist, losartan, was administered alone or in combination with the AT(2)-specific antagonist, PD123319, to preovulatory rat ovaries perfused in vitro. Losartan (100 micromol l(-1)) did not affect the number of ovulations, whereas the combination of losartan (100 micromol l(-1)) and PD123319 (10 micromol l(-1)) inhibited ovulation. The angiotensin II antagonists did not affect the ovarian production of oestradiol, progesterone, prostaglandin E(2) (PGE(2)), PGF(2 alpha) or plasminogen activator activity. Ovarian nitric oxide production was inhibited by losartan. Ovarian blood flow was measured by laser Doppler flowmetry in vivo in preovulatory rat ovaries. Intrabursal injection of angiotensin II reduced ovarian blood flow of gonadotrophin-stimulated rats. Losartan had no effect on basal ovarian blood flow but completely blocked the angiotensin II-induced reduction. In contrast, treatment with PD123319 increased basal ovarian blood flow and failed to reverse the effect of exogenously administered angiotensin II, indicating that under physiological conditions, ovarian blood flow of the rat is negatively regulated by angiotensin II mainly through the action of AT(2). Taken together, these results indicate that two different types of angiotensin II receptor facilitate ovulation by cooperative mechanisms and that they regulate ovarian blood flow in a different manner.

Angiotensin II↗

PubMed2002

Nitric oxide induced cervical ripening in the human: Involvement of cyclic guanosine monophosphate, prostaglandin F(2 alpha), and prostaglandin E(2).

OBJECTIVE: The purpose of the study was to investigate possible mechanisms and morphologic changes involved in nitric oxide-induced cervical ripening. STUDY DESIGN: Women scheduled for surgical termination of first trimester pregnancy were randomized to 1 of 3 groups: isosorbide 5-mononitrate 40 mg 4 hours or 10 hours before the operation or no preoperative treatment. Cervical specimens were obtained for the analysis of tissue levels of cyclic guanosine monophosphate, cyclic adenosine monophosphate, cyclo-oxygenase 1, cyclo-oxygenase 2, prostaglandin F(2 alpha), and prostaglandin E(2) or were fixed in glutaraldehyde for microscopy. RESULTS: Increased levels of cyclic guanosine monophosphate, cyclo-oxygenase 2, prostaglandin F(2 alpha), and prostaglandin E(2) were found in samples that were exposed to isosorbide 5-mononitrate compared with control samples. Electron microscopy revealed stromal edema and collagen disorganization after isosorbide 5-mononitrate treatment. CONCLUSION: Cyclic guanosine monophosphate, prostaglandin F(2 alpha), and prostaglandin E(2) are involved in nitric oxide-induced cervical ripening. Nitric oxide causes morphologic changes similar to those changes seen during spontaneous cervical ripening.

Cervical Ripening↗

PubMed2002

Heterotopic uterine transplantation by vascular anastomosis in the mouse.

A method of heterotopic uterine transplantation was developed in the mouse as a model system for studies of uterine function and transplant immunology of the uterus. The model involved transplantation of the right uterine horn and the cervix by vascular anastomosis to a donor animal with the intact native uterus remaining in situ. F1-hybrids of inbred C57BL/6 x CBA/ca (B6 CBAF1) mice of 6-8 weeks of age (n=42) were used. The specific pelvic vascular anatomy of these mice was first examined by intra-aortal injection of a two-component silicon-rubber curing agent. The surgery of the donor animal involved microsurgical isolation of the right uterine horn and the cervix, with preserved vascular supply from the aorta through the right uterine artery. After isolation of the uterine horn with vascular supply and venous drainage, including approximately 3 mm of the inferior vena cava and aorta, the organ was put on ice. The recipient animal was prepared by exposing and mobilizing the infrarenal part of the aorta and the vena cava. The grafted uterus was placed in the abdomen on the left side and the aorta and vena cava of the graft were anastomosed end-to-side to the aorta and vena cava of the recipient animal with 11-0 sutures. The total time for these procedures declined with time and was 125+/-4 min for the last 28 operations. Viability of the uterus was confirmed, several days later, by demonstrating a blood flow similar to that of the native uterus, and histology of the grafted uterus demonstrated normal morphology, including intact ultrastructure of the endothelial cells. The overall survival rate of the recipient animals increased with learning from approximately 40% in animals 1-21 to 71% in animals 22-42. The proportion of viable grafts, as judged by normal blood flow and histology among the surviving mice was 25% in animals 1-21 and 87% in animals 22-42. An undisturbed function of the transplanted uterus horn was finally demonstrated by its ability to implant inserted blastocysts and to carry pregnancy with fetal weight being similar to that of fetuses in the native uterus and controls. In conclusion, this is the first report of successful transplantation of the uterus with proven functionality in the mouse. The model should be useful for many aspects of research in uterine physiology and pathophysiology.

Anastomosis, Surgical↗

PubMed2001

Production of steroids by human ovarian surface epithelial cells in culture: possible role of progesterone as growth inhibitor.

OBJECTIVE: The purpose was to investigate whether normal ovarian surface epithelial cells, harvested from premenopausal and postmenopausal women, are capable of steroid production, and to evaluate effects of estradiol and progesterone on growth regulation of such cells. METHODS: Ovarian surface epithelial cells were obtained by brushing of the ovarian surface of 9 premenopausal and 10 postmenopausal women undergoing surgery for benign gynecological diseases. The conditioned media after culture, with and without addition of FSH and LH, were analyzed for estradiol and progesterone. The proliferative effects of the steroids were analyzed using two different culture models, nonconfluent cells and confluent cells, and two different detection methods, [(3)H]thymidine incorporation and a colorimetric method assaying cell number. RESULTS: The normal ovarian surface epithelial cells were found to secrete both estradiol and progesterone, a production that was not regulated by FSH or LH. Addition of steroids to the cultured cells did not induce any overall significant growth effects. However, progesterone significantly inhibited the growth of ovarian surface epithelial cells from three of the patients. Enhanced thymidine incorporation was observed in the presence of the progesterone receptor antagonist Org 31710 in the nonconfluent cultures of cells from postmenopausal women, but no effect of an estrogen receptor antagonist was observed. CONCLUSIONS: The normal ovarian surface epithelium is capable of steroid production, which is also often observed in tissue from ovarian epithelial tumors. Progesterone appeared to be a negative regulator of ovarian surface epithelial growth, while estradiol had no effect.

Aged↗

PubMed2001

Low peripheral blood levels of the immunosuppressive cytokine interleukin 10 (IL-10) at the start of gonadotrophin stimulation indicates increased risk for development of ovarian hyperstimulation syndrome (OHSS).

Our hypothesis was that patients developing ovarian hyperstimulation syndrome (OHSS) might have a disturbed responsiveness or delayed activation of the immunosuppresive cytokine system. In a prospective cohort study, women (n=428) undergoing in vitro fertilisation (IVF) treatment were subjected to repeated blood sampling and collection of clinical data. Fifteen patients, who developed severe OHSS, were compared with matched (age, follicle numbers, pregnancy) control patients. Samples of serum and plasma were collected throughout the stimulation and up to 7 days after embryo transfer as well as during hospitalisation for OHSS. Levels of IL-4, IL-10, IL-13, oestradiol and progesterone were measured. Significantly lower levels of IL-10 were seen at the start of gonadotrophin stimulation in OHSS patients, with an increase seen after the development of OHSS. In these OHSS patients, a negative correlation between IL-10 levels and number of follicles at time of aspiration existed, but there were no correlations between steroid and IL-10 levels. Levels of IL-13 and IL-4 were low in both groups and did not change during stimulation. The lower levels of IL-10 at start of stimulation in OHSS patients, as compared with controls, may be of pathophysiological importance by allowing for an enhanced Th-1 type immune response during gonadotrophin stimulation and thereby increased and generalised inflammation. The increase in IL-10 after development of OHSS indicates that IL-10 at that time is induced in a systemic attempt to suppress the inflammation of OHSS.

Cohort Studies↗

PubMed2001

Plasma levels of free vascular endothelial growth factor(165) (VEGF(165)) are not elevated during gonadotropin stimulation in in vitro fertilization (IVF) patients developing ovarian hyperstimulation syndrome (OHSS): results of a prospective cohort study with matched controls.

OBJECTIVE: To evaluate whether differences in plasma vascular endothelial growth factor(165) (VEGF(165)) concentrations exist during gonadotropin stimulation in IVF patients developing severe ovarian hyperstimulation syndrome (OHSS) compared to matched controls. STUDY DESIGN: Prospective cohort study with comparison of 15 OHSS cases with 30 matched (age, follicle numbers, pregnancy) controls. Unpaired students t-test was used to evaluate differences between the OHSS and control group and correlations were calculated with Pearson's test. RESULT(S): Plasma levels of VEGF(165), at four time-points from start of gonadotropin stimulation to embryo transfer (ET), were compared and related to steroid levels and ultrasound data. There were no differences between OHSS and control patients in plasma VEGF(165) levels at any of the four time points, which were compared. The mean levels were between 53--83 pg ml(-1) and 64--83 pg ml(-1) in the OHSS and control group, respectively. Positive correlations existed between total number of follicles, number of large (>15 mm) follicles and VEGF(165) at day of oocyte aspiration and between VEGF(165) and progesterone at ET in the control group, but not in the OHSS group. CONCLUSION(S): Patients developing OHSS do not have raised plasma VEGF(165) levels during gonadotropin stimulation. The lack of positive correlation between VEGF(165) levels and follicle numbers/progesterone in the OHSS group, suggests a disruption in OHSS of the normal controlled follicular VEGF expression.

Adult↗

PubMed2001

Changes in intrafollicular pressure in the rat ovary by nitric oxide and by alteration of systemic blood pressure.

BACKGROUND: ovulation is associated with degradation of the follicular apex vasodilatation and increased permeability of ovarian vessels. These changes may maintain or increase intrafollicular pressure (IFP) at ovulation to cause rupture of the follicular wall. OBJECTIVE: to investigate the possible regulation of IFP during the ovulatory process. STUDY DESIGN: immature Sprague-Dawley rats were primed with pregnant mare serum gonadotrophin (PMSG; 10IU) and given hCG (10IU) 48h later. The ovary was exposed 48-60h after PMSG, micropipette inserted into the Graafian follicle and the IFP measured at three time periods: preovulatory (PO) 48h after PMSG; midovulatory (MO) 4-7h after hCG; late ovulatory (LO) 9-12h after hCG. The offset of the nitric oxide synthase (NOS) inhibitor L-arginine methyl ester (L-NAME), the alpha(1)-adrenoceptor agonist phenylephrine and the beta-adrenoceptor agonist isoprenaline were tested. RESULTS: phenylephrine given i.v. increased the systemic blood pressure, and significantly decreased the IFP in the LO phase (78% of pre-treatment value). Local administration of phenylephrine or isoprenaline (1ml of 1.5-15 microM) by superfusion over the ovary did not change the IFP. Local administration of L-NAME (1ml of 2 microM) significantly lowered (P<0.05) the IFP in the MO and LO phases, but was without effect in the PO phase. CONCLUSION: this study reveals that IFP regulation may be related to changes of the systemic blood pressure and that NO may be one local ovarian mediator in IFP regulation.

Adrenergic alpha-Agonists↗

PubMed2001

Diverse effects of FSH and LH on proliferation of human ovarian surface epithelial cells.

The purpose of this study was to evaluate the effects of FSH and LH on growth regulation of normal ovarian surface epithelial (OSE) cells harvested from both premenopausal and postmenopausal women. Ovarian surface epithelial cells were obtained through brushing of the ovarian surface during surgery. FSH and LH were added to the OSE cultures and the proliferative effects were analysed using two different culture models, non-confluent and confluent cells, and two different detection methods, [(3)H]thymidine incorporation and a colorimetric cell number assay. FSH lowered the OSE proliferation under non-confluent conditions (10-27%), and the inhibitory effect was most pronounced among cells from postmenopausal women (P: < 0.01). In the confluent model only cells from postmenopausal women showed significantly (P: < 0.05) decreased proliferation. No effects of LH on OSE cells were detected. The unexpected results of an anti-proliferative effect of FSH on OSE, and the absence of effect by LH, do not support the theory that gonadotrophins are directly involved in ovarian carcinogenesis through an enhanced proliferation of OSE cells.

Adult↗

PubMed2001

Induction of delayed follicular rupture in the human by the selective COX-2 inhibitor rofecoxib: a randomized double-blind study.

BACKGROUND: The aims of the present study were to examine whether periovulatory administration of a cyclo-oxygenase (COX)-2 inhibitor affects human ovulation and endocrine parameters. METHODS: Thirteen healthy women, 30-40 years of age, without hormonal treatment and with regular menstrual cycles (27-34 days), were given the selective COX-2 inhibitor rofecoxib (n = 6) or placebo (n = 7) in a random double-blind fashion. In an initial control cycle, serial hormonal analyses, detection of a measurable mid-cycle urine LH peak and transvaginal ultrasound scans were performed to confirm normal ovulatory and endocrinological cyclic patterns, in all participating women. During the subsequent treatment cycle, serial ultrasound scans were performed. When the dominant follicle reached 14-16 mm in diameter, 25 mg rofecoxib or placebo was taken orally, once daily for 9 consecutive days, during which follicle size was monitored daily by ultrasound scans and serial hormone analyses were performed. RESULTS: Four of the six women who received rofecoxib demonstrated delayed follicle rupture, >48 h after the LH peak, when compared with the placebo group, who all had follicular rupture >36 h after the detected LH peak. No differences in peripheral serum concentrations of progesterone, oestradiol, LH and FSH were observed between placebo and rofecoxib groups, when analysed at specified time intervals. CONCLUSIONS: This study suggests that selective COX-2 inhibition has a negative, local effect on human ovulation, resulting in delayed follicular rupture, without affecting peripheral hormonal cyclicity.

Adult↗

PubMed2001

Plasma concentrations of nitrate during the menstrual cycle, ovarian stimulation and ovarian hyperstimulation syndrome.

BACKGROUND: Nitric oxide (NO) is predominantly a locally acting mediator, affecting several functions in the human female reproductive tract. In vivo, it is quickly metabolized to its stable end product nitrate, which is cleared by the kidney. METHODS AND RESULTS: The aim of the present study was to evaluate possible fluctuations of plasma nitrate concentrations during the menstrual cycle, ovarian stimulation as well as ovarian hyperstimulation syndrome (OHSS). During the menstrual cycle (n = 19 women) the mean nitrate concentrations were between 26.7 and 29.5 micromol/l at all stages except for the day of ovulation, when the concentrations were significantly (P < 0.001) increased (mean 37.2 micromol/l +/- 2.0). Significantly lower concentrations of plasma nitrate (P < 0.01) were measured at the end of gonadotrophin-releasing hormone (GnRH) down-regulation (24.6 micromol/l +/- 1.4) compared with the concentrations found at day 8 of follicle-stimulating hormone (FSH) stimulation (34.9 micromol/l +/- 2.6) and at the day of human chorionic gonadotrophin (HCG) (35.6 micromol/l +/- 3.3). The concentrations of nitrate (33.4 micromol/l +/- 3.4) in women with OHSS (n = 13) were similar to those seen 5 days after embryo transfer (33.2 micromol/l +/- 2.3). CONCLUSIONS: The results indicate that NO synthesis is increased at the time of spontaneous ovulation. GnRH treatment inhibits NO synthesis, while NO production is not increased in women with OHSS.

Adult↗

PubMed2001

Inhibition of ovulation in the rat by a leukotriene B(4) receptor antagonist.

The involvement of leukotriene (LT) B(4) in the ovulatory process of the rat was investigated by the use of a LTB(4)-receptor antagonist (ZK158252 = L-ANT) administered either intrabursally in vivo or to the in-vitro perfused ovary. The in-vivo experiments revealed inhibition of human chorionic gonadotrophin (HCG)-induced ovulation by 500 micromol/l L-ANT (median 5.5, 25-75% range 1.0-6.0) compared with controls (median 9.0, range 6.25-13.5). In vitro, ovulation was induced by LH (0.2 microg/ml) + 3-isobutyl-1-methylxanthine (IBMX; 0.2 mmol/l). The ovary was perfused either for 20 h, to study ovulation rate, or for 10 h to examine ovarian concentrations of the ovulatory mediators matrix metalloproteinase (MMP)-2 and MMP-9, plasminogen activator (PA), prostaglandin (PG)E(2) and PGF(2 alpha). Addition of LH+IBMX resulted in a marked stimulation of steroid release and ovulations occurred in all ovaries (median 11.0, range 10.0-14.0). The L-ANT inhibited ovulation in a dose-dependent way (median 10.0, range 8.0-13.0 at 1 micromol/l; median 6.0, range 3.5-10.0 at 10 micromol/l; median 2.0, range 0.75-5.75 at 100 micromol/l). The intra-ovarian activity of PA was increased 1.5-fold by L-ANT (100 micromol/l), but the concentrations of PGE(2) and PGF(2 alpha) remained unaltered. While no changes in MMP-9 were observed, conversion from pro-MMP-2 to active MMP-2 was inhibited by L-ANT. These results suggest that activation of the LTB(4)-receptor within the ovary is involved in the ovulatory process and that the effects of LTB(4)-receptor activation are partly mediated via MMP-2.

Animals↗