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Biology of Reproduction 61, 436-443 (1999)
©Copyright 1999 Society for the Study of Reproduction, Inc.

Articles

Inter-{alpha}-Inhibitor Binding to Hyaluronan in the Cumulus Extracellular Matrix Is Required for Optimal Ovulation and Development of Mouse Oocytes1

Karla A. Hessa,b, Lin Chenc, and William J. Larsen2,c

a Molecular and Developmental Biology, b Children's Hospital Research Foundation, c Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0521

This report characterizes the effects of excess hyaluronan (HA) upon the expansion of the cumulus oocyte complex (COC) within intact follicles and upon ovulation and oocyte viability in mice. Covalent linkage between heavy chains of the inter-{alpha}-inhibitor (I{alpha}I) family of serum glycoproteins and HA is necessary for optimal cumulus extracellular matrix (cECM) stabilization and cumulus expansion. Intravenous administration of HA oligosaccharides inhibited the binding of I{alpha}I to endogenous HA, disrupting the process 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 compared to control animals. The developmental potential of COCs in HA-treated animals was also tested. Extended periods of oviductal storage of COCs ovulated by HA-injected adult mice resulted in a reduction of normal embryos and a significant increase in the proportion of fragmented oocytes/embryos. These observations support the view that covalent binding of I{alpha}I heavy chains to HA is required for optimal cumulus expansion, extrusion of the COCs from the follicle at ovulation, and maintenance of oocyte viability within the oviduct.

1 This work was supported by grants from NIH (HD07463–02 and HD-29894–04A2) and the Albert J. Ryan Fellowship Foundation.

2 Correspondence: William J. Larsen, Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati, College of Medicine, PO Box 670521, Cincinnati, OH 45267–0521. FAX: 51 558 4454; william.larsen{at}uc.edu




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Copyright © 1999 by the Society for the Study of Reproduction.