Inter-alpha-inhibitor binding to hyaluronan in the cumulus extracellular matrix is required for optimal ovulation and development of mouse oocytes

This report characterizes the effects of excess hyaluronan (HA) upon the ex pansion of the cumulus oocyte complex (COC) within intact follicles and upo n ovulation and oocyte viability in mice. Covalent linkage between heavy ch ains of the inter-alpha-inhibitor (I alpha I) family of serum glycoproteins and HA is necessary for optimal cumulus extracellular matrix (cECM) stabil ization and cumulus expansion. Intravenous administration of HA oligosaccha rides inhibited the binding of I alpha I to endogenous HA, disrupting the p rocess of expansion and resulting in a reduction in the size of the cumulus mass. Western blot and immunocytochemical analyses of COCs from HA-treated animals demonstrated a reduction of I alpha I heavy chains within the cECM . Additionally, HA-treated immature animals ovulated 56.3% fewer COCs compa red to control animals. The developmental potential of COCs in HA-treated a nimals was also tested. Extended periods of oviductal storage of COCs ovula ted by HA-injected adult mice resulted in a reduction of normal embryos and a significant increase in the proportion of fragmented oocytes/embryos. Th ese observations support the view that covalent binding of I alpha I heavy chains to HA is required for optimal cumulus expansion, extrusion of the CO Cs from the follicle at ovulation, and maintenance of oocyte viability with in the oviduct.