ABSTRACT. Cumulus oophorus, an investing structure unique to oocytes of higher mammals, is induced to synthesize an extensive extracellular matrix by ovulatory stimulus, leading to the characteristic preovulatory expansion of the cumulus-oocyte complex. The extracellular matrix consists of cumulus cell-secreted hyaluronan, proteoglycans and proteins, as well as extrafollicularly originated SHAPs (serum-derived hyaluronan-associated proteins) that are bound covalently to hyaluronan. The secretion and assembly of matrix molecules by cumulus cells are temporally regulated by factors derived from both mural granulosa cells and oocyte, which synchronize the deposition of the cumulus oophorus matrix with other intrafollicular ovulatory events. The cumulus oophorus matrix is essential for ovulation and subsequent fertilization. Recently, taking advantage of animal models with defined genetic modifications, it has become possible to investigate in vivo the structure of the cumulus oophorus matrix, the regulatory mechanism for matrix deposition and its biological functions. This review focuses on the recent findings on the construction of the cumulus oophorus matrix and the regulation.Key words: extracellular matrix/hyaluronan/SHAP-HA complex/proteoglycan/ovulation/fertilization During late stages of folliculogenesis in higher mammals, a population of follicular granulosa cells forms a specific cumulus oophorus structure in the periphery of the ovum. In mice, a cumulus oophorus structure consists of about 3,000-5,000 cumulus cells that are held together by a gap junction network and subsequently by an extensive extracellular matrix after the physiological ovulatory stimulation of luteinizing hormone (LH) surge. The preovulatory deposition of cumulus oophorus matrix causes a characteristic volumetric enlargement of the cumulus-oocyte complex (COC) (about 20-40 times the initial volume) and dissociation of COC from the follicle wall, accompanied by the resumption of oocyte meiosis that is characterized by germinal vesicle breakdown and extrusion of the first polar body. At the same time, LH surge also stimulates active steroidogenesis, prostaglandin/leukotriene synthesis and matrix-degrading protease secretion in mural granulosa cells and theca cells, and great changes in the permeability of the follicle-blood barriers, leading to accumulation of follicle fluid and increase of intrafollicular pressure. As a result, the follicle wall ruptures to extrude COC. The expanded cumulus oophorus structures often remain investing the oocytes in oviducts until several hours after fertilization (Fig. 1). The cumulus oophorus structure is thus thought to play important roles in oocyte development, ovulation and fertilization in higher mammals.
The cumulus oophorus matrix is a hyaluronanrich matrixThe cumulus oophorus matrix is rich in hyaluronan (HA) as shown by studies on HA synthesis (Salustri et al., 1989), sensitivity to hyaluronidase (Talbot et al., 1984), and inhibition of matrix formation by HA oligomers or HA synthesis inhibito...