| 1. |
- Dahm-Kähler, Pernilla, 1964, et al.
(författare)
-
Monocyte chemotactic protein-1 (MCP-1), its receptor, and macrophages in the perifollicular stroma during the human ovulatory process
- 2009
-
Ingår i: Fertility and Sterility. - : Elsevier BV. - 1556-5653 .- 0015-0282. ; 91:1, s. 231-239
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the expression and localization of the macrophage-specific chemokine monocyte chemotactic protein-1 (MCP-1), CC chemokine receptor 2 (CCR2), and macrophages (CD68) in the perifollicular stroma of different phases of the human ovulatory process and its relation to macrophage influx. DESIGN: Experimental study on patient-controlled material. SETTING: University hospital. PATIENT(S): Twenty-eight women planned to undergo laparoscopic sterilization. INTERVENTION(S): Surgery was performed at either of four distinct ovulatory phases, and a biopsy sample was obtained from the perifollicular stroma of the ovulatory follicle. MAIN OUTCOME MEASURE(S): Real-time polymerase chain reaction, immunoblotting, and immunohistochemistry were used for measurements of MCP-1, CCR2, and macrophages. RESULT(S): The messenger RNA levels of MCP-1 in the perifollicular stroma increased from the preovulatory to the late ovulatory phase and declined during the postovulatory phase. A higher density of macrophages was found in the preovulatory and early ovulatory phases compared with late and postovulatory phases. Monocyte chemotactic protein-1 and CCR2 were present in the stroma. Protein expression of CD68 and CCR2 were identified in the four ovulatory phases. CONCLUSION(S): This study demonstrates an upregulation of MCP-1 in the stroma compartment around the human follicle during the ovulatory process, and a high density of macrophages was found at earlier phases. Thus, inflammation-like reactions are integral in the ovulatory process and may be targeted to stimulate or inhibit this process.
|
|
| 2. |
- Lind, Anna Karin, 1962, et al.
(författare)
-
Collagens in the human ovary and their changes in the perifollicular stroma during ovulation
- 2006
-
Ingår i: Acta Obstet Gynecol Scand. ; 85:12, s. 1476-84
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Remodeling of the collagens around the follicle is a major event in ovulation. The aim of the present study was to investigate the distribution of collagen I, III, and IV in the human ovary. METHODS: Biopsies of the perifollicular stroma were obtained at sterilization during the preovulatory phase (follicle size >14 mm) or at any of three intervals (12-18 h after human chorionic gonadotrophin: early ovulatory phase; >18-24 h: late ovulatory phase; 44-77 h: postovulatory phase) after human chorionic gonadotrophin. Excised dominant follicles and whole ovarian sections were also obtained. Immunohistochemistry using antibodies against collagen I, III, IV, vimentin, and CD 45 was performed. RESULTS AND CONCLUSIONS: Collagens I and III were distributed in concentric layers in the capsular stroma with bundles of collagens connecting these layers to form a mesh. Collagen I was present in larger quantities in the outer layers and collagen III showed the inverse distribution. In the theca, collagen I was present in the externa and collagen III in the entire layer. The staining intensity of collagens I and III in the perifollicular stroma decreased from the preovulatory stage. Collagen IV was present in the basal lamina separating granulosa and theca cells. This study shows that collagen I and III are abundant in and around the ovulating human follicle with typical patterns of distribution. Collagen IV is present in the basal membrane that separates the granulosa from the theca cells. Taking into account the abundance of collagens in the follicular wall and their specific localization, major site-directed degradation of collagens seems to be necessary for follicular rupture to occur.
|
|
| 3. |
- Lind, Anna Karin, 1962, et al.
(författare)
-
Gelatinases and their tissue inhibitors during human ovulation: increased expression of tissue inhibitor of matrix metalloproteinase-1
- 2006
-
Ingår i: Mol Hum Reprod. ; 12:12, s. 725-36
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 4. |
- Jedel, Elizabeth, 1962, et al.
(författare)
-
Anxiety and depression symptoms in women with polycystic ovary syndrome compared with controls matched for body mass index.
- 2010
-
Ingår i: Human reproduction. - : Oxford University Press (OUP). - 1460-2350 .- 0268-1161. ; 25:2, s. 450-456
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Anxiety and depression are more prevalent in women with polycystic ovary syndrome (PCOS) than in those without this disorder. Possible confounding effects of overweight and obesity are suggested. The aim was to compare symptoms of anxiety and depression in women with PCOS and controls matched for age, body weight and body mass index (BMI). METHODS Women with PCOS (n = 30) and controls (n = 30) were recruited from the community. Persons with ongoing psychotropic medication were excluded. All potential participants underwent gynecological examination to confirm case-control status. Participants completed the self-reported versions of the Brief Scale for Anxiety (BSA-S) and Montgomery Asberg Depression Rating Scale (MADRS-S). RESULTS Women with PCOS had a higher BSA-S score compared with controls (median, range: 10.5, 1-24 versus 5.0, 0-28, P < 0.001). They scored higher on the following four individual symptoms: reduced sleep (2.0, 0-5 versus 0, 0-2, P < 0.001), worry (1.5, 0-4 versus 0, 0-6, P = 0.004), phobias (1, 0-4 versus 0, 0-3, P < 0.001), and pain (1, 0-3 versus 0, 0-2, P < 0.001). No statistical difference was demonstrated regarding MADRS-S scores (10.0, 0-27 versus 5.5, 0-24, P = 0.053). Only one of the nine MADRS-S symptoms, reduced sleep, which is also included in the BSA-S, differed between cases and controls. CONCLUSIONS Several anxiety symptoms distinguished women with PCOS from a control group matched on BMI. A better understanding of the symptoms is needed to identify and alleviate anxiety symptoms in this vulnerable group.
|
|
| 5. |
- Jedel, Elizabeth, 1962, et al.
(författare)
-
Impact of electroacupuncture and exercise on hyperandrogenism and oligo/amenorrhoea in women with polycystic ovary syndrome: A randomized controlled trial.
- 2011
-
Ingår i: American Journal of Physiology - Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 300:1, s. E37-45
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism, oligo/amenorrhea, and polycystic ovaries. We aimed to determine whether low-frequency electro-acupuncture (EA) decreases hyperandrogenism and improves oligo/amenorrhea more effectively than physical exercise or no intervention. Methods: We randomized 84 women with PCOS, aged 18-37 years, to 16 weeks of low-frequency EA, physical exercise, or no intervention. The primary outcome measure-changes in the concentration of total testosterone (T) at week 16 determined by gas and liquid chromatography/mass spectrometry-was analyzed by intention-to treat. Secondary outcome measures were changes in menstrual frequency; concentrations of androgens, estrogens, androgen precursors, glucuronidated androgen metabolites; and acne and hirsutism. Outcomes were assessed at baseline, after 16 weeks of intervention, and after a 16-week follow-up. Results: After 16 weeks of intervention, circulating T decreased by -25%, androsterone glucuronide by -30%, and androstane-3α, 17β-diol-3glucuronide by -28% in the EA group (P=0.038, 0.030, and 0.047, respectively vs. exercise); menstrual frequency increased to 0.69/month from 0.28 at baseline in the EA group (P=0.018 vs. exercise). After the 16-week follow-up, the acne score decreased by -32% in the EA group (P=0.006 vs. exercise). Both EA and exercise improved menstrual frequency and decreased the levels of several sex steroids at week 16 and at the 16-week follow-up, compared to no intervention. Conclusion/Significance: Low-frequency EA and physical exercise improved hyperandrogenism and menstrual frequency more effectively than no intervention in women with PCOS. Low-frequency EA was superior to physical exercise and may be useful for treating hyperandrogenism and oligo/amenorrhea.
|
|
| 6. |
- Dahm-Kähler, Pernilla, 1964, et al.
(författare)
-
Monocyte chemotactic protein-1 in the follicle of the menstrual and IVF cycle
- 2006
-
Ingår i: Mol Hum Reprod. ; 12:1, s. 1-6
-
Tidskriftsartikel (refereegranskat)abstract
- Ovulation constitutes an inflammatory-like process, with macrophages migrating into the follicle. This study evaluates the production of two macrophage-specific chemokines, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha), in the human follicle at ovulation. Blood samples, follicular fluids and follicular cells were collected during menstrual and IVF cycles. Levels of MCP-1 and MIP-1alpha were measured in follicular fluid, blood plasma and cultured media (granulosa, theca and granulosa-lutein cells [GLCs]). Cells were cultured with or without LH, FSH, interleukin (IL)-1alpha, IL-1beta, tumour necrosis factor (TNF) alpha, progesterone or estradiol. The levels of MCP-1 were markedly higher in follicular fluid as compared with blood plasma in both menstrual and IVF cycles. The difference in MCP-1 levels between follicular fluid and plasma in menstrual cycles increased from the follicular phase (three-fold difference) to the late ovulatory phase (25-fold). Levels of MIP-1alpha were low in plasma and follicular fluid of both menstrual and IVF cycles. Theca cells from follicles of menstrual cycles secreted both MCP-1 and MIP-1alpha under basal conditions, and the secretion was increased by addition of IL-1beta (MCP-1 and MIP-1alpha) and IL-1alpha (MCP-1). GLCs secreted MCP-1 under basal conditions and also MIP-1alpha after IL-1beta stimulation. The macrophage-specific chemokine MCP-1 is highly expressed and is induced by IL-1 in the theca layer of the human follicle at ovulation.
|
|
| 7. |
- Leonhardt, Henrik, 1963, et al.
(författare)
-
Ovarian morphology assessed by magnetic resonance imaging in women with and without polycystic ovary syndrome and associations with antimullerian hormone, free testosterone, and glucose disposal rate.
- 2014
-
Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 101:6
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract OBJECTIVE: To characterize ovarian morphology and perfusion by magnetic resonance imaging (MRI) in women with and without polycystic ovary syndrome (PCOS) and to investigate associations with antimüllerian hormone (AMH), free T, and glucose disposal rate (GDR). DESIGN: Explorative cross-sectional study. SETTING: University hospital. PATIENT(S): Fifty-eight women with PCOS and 31 controls from the general population. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Antral follicle count (AFC), ovarian/stromal volume, perfusion, AMH, free T, and GDR. RESULT(S): Antral follicles of 1-3 and 4-6 mm, but not 7-9 mm, were more numerous, and total AFC (1-9 mm) was higher in women with PCOS. Ovarian volume was larger in women with PCOS. AMH and free T were higher and GDR was lower in women with PCOS. All values were more deranged in classic compared with nonclassic PCOS. There was a positive correlation between AMH and AFC, 1-3 mm (r = 0.81), and between AMH and total AFC (r = 0.87). In receiver operating characteristic analyses, the area under the curve was 0.89 for total AFC, 0.86 for AMH, and 0.90 for free T. PCOS was independently associated with AFC and free T but not with AMH or GDR when adjusted for age and body mass index. CONCLUSION(S): Counting antral follicles down to 1 mm in size by MRI yielded higher AFCs than previously reported. AFC, AMH, and free T discriminated with high accuracy between women with PCOS and controls, but AMH was not independently associated with PCOS.
|
|
| 8. |
|
|
| 9. |
- Lind, Anna Karin, 1962
(författare)
-
Human ovulation. Studies on collagens, gelatinases and tissue inhibitors of metalloproteinases.
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ovulation is a highly regulated process, which involves the degradation and rupture of healthy tissue of the ovarian follicle and the extrusion of a fertilizable oocyte. This unique biological process is initiated by the LH-surge, which induces major vascular changes and remodelling of the extracellular matrix (ECM) in and around the follicle. The collagens of the ECM make up the tensile strength of the follicle wall and breakdown of these proteins seems to be a prerequisite for follicular rupture to occur. There is now robust evidence that matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) are crucial in this process. Earlier studies in this field have been mostly animal studies. The general aims of this thesis were to investigate the distribution of three types of collagens in the human ovary and to explore the expression patterns of the gelatinases, MMP-2 and MMP-9, together with their endogenous inhibitors, TIMP-2 and TIMP-1, during ovulation. The study was approved by the human Ethics Committee of Sahlgrenska Academy, Göteborg University. Informed written consent was obtained from all women participating in the study. Women, planned for laparoscopic sterilization participated in the study. They were closely monitored by transvaginal ultrasound. Surgery was performed during either of four distinct ovulatory phases and the dominant follicle and its adjacent stroma was excised. Granulosa and theca cells were harvested. Whole ovarian sections from premenopausal women undergoing oophorectomy at surgery for cervical cancer or due to familial predisposition to ovarian cancer were also obtained. The distribution of collagen types I, III and IV in biopsies of the perifollicular stroma from four distinct ovulatory phases as well as in whole ovarian sections was investigated by immunohistochemistry (paper I). Collagen types I and III were abundant in the perifollicular stroma around the periovulatory human follicle. These types of collagen were also present in a typical concentric layered pattern in the stromal capsule of the ovary making up a scaffold for the ovarian tissue. Collagen type IV was present in the basal lamina that separates the granulosa from the theca cells. The staining intensity of collagens type I and III in the perifollicular stroma decreased from preovulatory stage throughout ovulation indicating a degradation of the follicle wall. In paper II-IV, MMP-2, MMP-9 and TIMP-2 and TIMP-1 were found to be present in the stroma-, theca and granulosa cells compartment of the periovulatory follicle. The protein levels of these enzymes and inhibitors were examined by Western Blot in paper II. In paper II-IV mRNA expression was demonstrated by real time PCR and the protein distribution by immunohistochemistry. An increase of TIMP-1 was seen in the perifollicular stroma both on the protein- and mRNA- level. In the granulosa- and theca cells compartments a large increase in TIMP-1 and MMP-9 mRNA was demonstrated. Immunostaining for MMP-2, MMP-9, TIMP-2 and TIMP-1 was visualized in the different compartments of the periovulatory folllcle. In summary, the abundance of collagens in the human follicular wall and their specific localization suggest that major site-directed degradation of collagens is necessary for follicular rupture to occur. This is the first study that has demonstrated an ovulation-associated expression of the ECM remodelling enzyme, MMP-9, together with its endogenous inhibitor, TIMP-1, in and around the human follicle at ovulation. Increasing knowledge concerning these aspects of human ovulation could contribute to the development of clinical treatments of anovulation and also to the discovery of new contraceptive strategies that could inhibit ovulation on the ovarian level without the side effects of the oral contraceptives used today.
|
|
| 10. |
- Park, Eun-Sil, et al.
(författare)
-
RUNX2 Transcription Factor Regulates Gene Expression in Luteinizing Granulosa Cells of Rat Ovaries
- 2010
-
Ingår i: MOLECULAR ENDOCRINOLOGY. - 0888-8809. ; 24:4, s. 846-858
-
Tidskriftsartikel (refereegranskat)abstract
- The LH surge promotes terminal differentiation of follicular cells to become luteal cells. RUNX2 has been shown to play an important role in cell differentiation, but the regulation of Runx2 expression and its function in the ovary remain to be determined. The present study examined 1) the expression profile of Runx2 and its partner CBFβ during the periovulatory period, 2) regulatory mechanisms of Runx2 expression, and 3) its potential function in the ovary. Runx2 expression was induced in periovulatory granulosa cells of human and rodent ovaries. RUNX2 and core binding factor-β (CBFβ) proteins in nuclear extracts and RUNX2 binding to a consensus binding sequence increased after human chorionic gonadotropin (hCG) administration. This in vivo up-regulation of Runx2 expression was recapitulated in vitro in preovulatory granulosa cells by stimulation with hCG. The hCG-induced Runx2 expression was reduced by antiprogestin (RU486) and EGF-receptor tyrosine kinase inhibitor (AG1478), indicating the involvement of EGF-signaling and progesterone-mediated pathways. We also found that in the C/EBPβ knockout mouse ovary, Runx2 expression was reduced, indicating C/EBPβ-mediated expression. Next, the function of RUNX2 was investigated by suppressing Runx2 expression by small interfering RNA in vitro. Runx2 knockdown resulted in reduced levels of mRNA for Rgc32, Ptgds, Fabp6, Mmp13, and Abcb1a genes. Chromatin immunoprecipitation analysis demonstrated the binding of RUNX2 in the promoter region of these genes, suggesting that these genes are direct downstream targets of RUNX2. Collectively, the present data indicate that the LH surge-induced RUNX2 is involved in various aspects of luteal function by directly regulating the expression of diverse luteal genes.
|
|
