Extracellular Matrix of the Cumulus-Oocyte Complex

University of Rome Tor Vergata, Roma, Latium, Italy
Seminars in Reproductive Medicine (Impact Factor: 2.35). 10/2006; 24(4):217-27. DOI: 10.1055/s-2006-948551
Source: PubMed


The mammalian oocyte is surrounded by several layers of cumulus granulosa cells that nurture the oocyte during its development and actively participate in the process of ovulation. After the ovulatory luteinizing hormone surge, a distinctive program of extracellular matrix production is initiated in the cumulus-oocyte complex. This process known as cumulus expansion or mucification involves synthesis of a backbone of long hyaluronan oligosaccharide chains that are cross-linked by a complex of hyaluronan binding cell surface and extracellular matrix proteins and proteoglycans. Active components of the cumulus matrix are synthesized directly by cumulus cells under the control of endocrine- and oocyte-derived factors, secreted by mural granulosa cells, or enter the follicle in blood plasma. Appropriate composition and assembly of the cumulus matrix is essential for ovulation, efficient passage of the oocyte through the oviduct, and for fertilization. This review describes the critical components and their functional roles in the cumulus matrix, as well as the molecular regulation of cumulus matrix gene expression.

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    • "The overstimulation of a number of genes that code for secreted proteins involved in matrix formation and adhesion might be partially explained by the absence, during IVM in serum free media, of different signals from the follicular environment that are required for regulating the production and secretion of matrix-related proteins (Russell and Salustri, 2006). Thus, a high expression level of these genes may be maintained continuously in CC in vitro whereas the in vivo background might suppress them when an optimal level of matrix production was achieved. "
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    ABSTRACT: In vitro maturation (IVM) of immature oocytes is widely used in assisted reproduction technologies in cattle, and is increasingly used to treat human infertility. The development competence of IVM oocytes, however, is lower than preovulatory, in vivo-matured oocytes. During maturation, cumulus cells (CC) are metabolically coupled with an oocyte and support the acquisition of its developmental potential. Our objective was to identify genes and pathways that were affected by IVM in bovine CC. Microarray transcriptomic analysis of CC enclosing in vitro- or in vivo-mature oocytes revealed 472 differentially expressed genes, including 28% related to apoptosis, correlating with 2-fold higher cell death after IVM than in vivo, as detected by TUNEL. Genes overexpressed after IVM were significantly enriched in functions involved in cell movement, focal adhesion, extracellular matrix function, and TGF-beta signalling, whereas under-expressed genes were enriched in regulating gene expression, energy metabolism, stress response, and MAP kinases pathway functions. Differential expression of 15 genes, including PAG11 (increased) and TXNIP (decreased), which were never detected in cumulus cells before, was validated by real time RT-PCR. Moreover, protein quantification confirmed the lower abundance of glutathione S-transferase A1 and prostaglandin G/H synthase 2, and the higher abundance of hyaluronan synthase 2 and SMAD4, a member of TGF-beta pathway, in CC after IVM. Phosphorylation levels of SMAD2, MAPK3/1, and MAPK14, but not MAPK8, were higher after IVM that in vivo. In conclusion, IVM provokes the hyper-activation of TGF-beta and MAPK signaling components, modifies gene expression, leads to increased apoptosis in CC, and thus affects oocyte quality. Mol. Reprod. Dev. © 2012 Wiley Periodicals, Inc.
    Molecular Reproduction and Development 02/2013; 80(2). DOI:10.1002/mrd.22148 · 2.53 Impact Factor
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    • "In the mature antral follicle, the cumulus cells secrete hyaluronic acid, a type of glycosaminoglycan that binds to cumulus cells via linker proteins. As the hyaluronate is hydrated, the cumulus cells spread apart and become entrenched in a mucified extracellular matrix [22, 23]. This expands the volume of the cumulus-oophorus complex (COC) to almost 20–40 times its initial volume [24]. "
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    ABSTRACT: Introduction. Sexual dimorphism with an increased prevalence in women has long been observed in various autoimmune, allergic, and skin diseases. Recent research has attempted to correlate this female predilection to physiologic changes seen in the menstrual cycle in order to more effectively diagnose and treat these diseases. Cases. We present five cases of cutaneous diseases in women with annular morphology and distributive features that favor one side over the other. In all cases, skin disease improved with ovarian suppression. Conclusion. Sexual dimorphism in the innate and adaptive immune systems has long been observed, with females demonstrating a more vigorous immune response compared to males. Female sex hormones promote T and B lymphocyte autoreactivity and favor the humoral arm of adaptive immunity. In addition to ovarian steroidogenesis and immunity, intricate pathways coexist in order to engage a single oocyte in each cycle, while simultaneously sustaining the ovarian reserve. Vigorous proinflammatory, vasoactive, and pigment-related cytokines emerge during the demise of the corpus luteum, influencing peripherical sex hormone metabolism of the level of the macrophage and fibroblast. We propose that annular and lateralizing lesions are important manifestations of hormone-related inflammation and recognition of this linkage can lead to improved immune and reproductive health.
    Journal of Allergy 12/2012; 2012:604854. DOI:10.1155/2012/604854
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    • "During maturation, the CC synthesised the active components of extracellular matrix under the control of endocrine-and oocyteproduced factors. Consequent extensive expansion of the cumulus is essential for ovulation, efficient passage of the oocyte through the oviduct, and for fertilization in vivo [12] [16] [17] and in vitro [18]. EGF and FSH have a proven beneficial effect on oocyte developmental competence during IVM [19] [20] [21] and act likely through CC, which expressed FSH receptor, FSHR [22]. "

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