Monocyte chemotactic protein-1 in the follicle of the menstrual and IVF cycle

Department of Obstetrics and Gynecology, University of Gothenburg, Goeteborg, Västra Götaland, Sweden
Molecular Human Reproduction (Impact Factor: 3.75). 02/2006; 12(1):1-6. DOI: 10.1093/molehr/gah256
Source: PubMed


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.

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    • "Thus, probing follicular fluid collected at the time of oocyte retrieval may help to provide suitable biochemical markers of oocyte quality.[10] Several previous reports have indicated the putative, but often inconclusive value of specific individual cytokines, chemokines, growth factors and hormones in follicular fluid collected at the time of oocyte retrieval as likely predictors of successful pregnancy in IVF cycles.[1112131415161718192021222324] It has been suggested that multiplex analysis to explore the pattern of expression of a cohort of cytokines, chemokines and growth factors of follicular fluid may reveal robust indication of oocyte quality.[2526] "
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    ABSTRACT: Conflicting results were yielded about the superiority of gonadotropin-releasing hormone agonist (GnRH-a) versus gonadotropin-releasing hormone antagonist (GnRH-ant) protocols used in ovarian stimulation in in vitro fertilization (IVF) set-up. Reports also indicate that any single specific individual marker in follicular fluid collected at the time of oocyte retrieval bears inconclusive value as a predictor of oocyte quality. Simultaneous analyses of large numbers of cytokines, chemokines and growth factors in ovarian follicular fluid and perifollicular vascularity in both protocols for ovarian stimulation in IVF program to address the above mentioned lacunae. Normoresponder women (n = 45) were subjected to either GnRH-a (Group 1; n = 23) or GnRH-ant (Group 2; n = 22) for ovarian stimulation in IVF clinics. The fluid samples of dominant follicles collected at oocyte retrieval from women in Group 1 (GnRH-a; n = 20) and Group 2 (GnRH-ant; n = 16) were used for simultaneous quantitative assays of 48 cytokines. Perifollicular vascularity was assessed by Doppler hemodynamics to assess the ovarian vascular response in all participants in Groups 1 and 2. Despite demographic and reproductive parameters studied remained comparable, higher follicular fluid concentration of interleukins, IL-3 (P < 0.01), IL12p70 (P < 0.05) and vascular endothelial growth factor (P < 0.01), P4 (P < 0.05) and pulsatility index (P < 0.04) along with a lower number of oocytes in metaphase II stage (P < 0.03) was observed in Group 2 compared with Group 1. GnRH-a protocol appeared to be superior to GnRH-ant protocol for ovarian stimulation in normoresponder women.
    Full-text · Article · Mar 2013 · Journal of Human Reproductive Sciences
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    • "Third, GL cells secrete steroid hormones , which have pleiotropic effects on immune cells (Bouman et al., 2005). Four, ovarian granulosa cells secrete, beyond IL-8, additional chemokines that may periodically direct specific leukocyte subsets to the ovary, including monocyte chemoattractant protein-1, growth-regulated-a and fractalkine (Karströ m-Encrantz et al., 1998; Dahm-Kahler et al., 2006; Zhao et al., 2008). The ovary, besides placenta, is a unique site of physiological angiogenesis in adults. "
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    ABSTRACT: Leukocyte infiltration and angiogenesis in the forming corpus luteum are prerequisites for normal ovarian function and may also underlie disorders like ovarian hyperstimulation syndrome. We examined whether ovarian angiogenesis could be affected by an interaction between granulosa-lutein (GL) cells and leukocytes. We found that GL cells isolated from the follicular fluid synthesize and secrete the chemokine interleukin-8 (IL-8), which activates IL-8-receptor-specific Ca(2+) and p38 mitogen-activated protein kinase signalling in monocytes and induces a directed migration of these cells towards the chemical gradient. Monocytes were found to further enhance IL-8 release, which suggests that these cells promote a massive leukocyte infiltration of the forming corpus luteum. A possible utility of leukocyte infiltration is the modulation of angiogenesis. We found that GL cells induce migration and capillary tube formation by endothelial cells in vitro. Furthermore, monocytes altered the profile of angiogenic factors released by GL cells, which supports the theory that an interaction between GL cells and leukocytes regulates ovarian angiogenesis. In addition, we found a correlation between increased secretion of pro-angiogenic cytokines and number of oocytes collected during IVF, which suggests that ovarian angiogenesis is related to the clinical response during ovarian stimulation. An intricate communication may exist between infiltrating leukocytes and ovarian GL cells during the formation of corpus luteum, affecting neo-vascularization of the luteal tissue.
    Full-text · Article · Aug 2011 · Human Reproduction
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