Impaired cumulus mucification and female sterility in tumor necrosis factor-induced protein-6 deficient mice

Mucification of the cumulus layer around the oocyte is an obligatory process for female fertility. Tumor necrosis factor-induced protein-6 (TNFIP6 or TSG6) has been shown to be specifically expressed during this process. We have generated TNFIP6-deficient mice and tested the ability of their cumulus...

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Published in:	Development (Cambridge) Vol. 130; no. 10; pp. 2253 - 2261
Main Authors:	Fülöp, Csaba, Szántó, Sándor, Mukhopadhyay, Durba, Bárdos, Tamás, Kamath, Rajesh V., Rugg, Marylin S., Day, Anthony J., Salustri, Antonietta, Hascall, Vincent C., Glant, Tibor T., Mikecz, Katalin
Format:	Journal Article
Language:	English
Published:	England The Company of Biologists Limited 15-05-2003
Subjects:	Animals Cell Adhesion Molecules - genetics Cell Adhesion Molecules - metabolism Extracellular Matrix - metabolism Female Genotype Humans Hyaluronic Acid - chemistry Hyaluronic Acid - metabolism Infertility, Female Male Mice Mice, Knockout Oocytes - cytology Oocytes - physiology Ovary - anatomy & histology Ovary - pathology Recombinant Proteins - genetics Recombinant Proteins - metabolism
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Summary:	Mucification of the cumulus layer around the oocyte is an obligatory process for female fertility. Tumor necrosis factor-induced protein-6 (TNFIP6 or TSG6) has been shown to be specifically expressed during this process. We have generated TNFIP6-deficient mice and tested the ability of their cumulus cells to undergo mucification. Cumulus cell-oocyte complexes fail to expand in TNFIP6-deficient female mice because of the inability of the cumulus cells to assemble their hyaluronan-rich extracellular matrix. The impaired cumulus matrix formation is due to the lack of covalent complexes between hyaluronan and the heavy chains of the inter-Î±-trypsin inhibitor family. As a consequence, TNFIP6-deficient females are sterile. Cultured TNFIP6-deficient cumulus cell-oocyte complexes also fail to expand when stimulated with dibutyryl cyclic AMP or epidermal growth factor. Recombinant TNFIP6 is able to catalyze the covalent transfer of heavy chains to hyaluronan in a cell-free system, restore the expansion of Tnfip6 -null cumulus cell-oocyte complexes in vitro, and rescue the fertility in Tnfip6 -null females. These results provide clear evidence that TNFIP6 is a key catalyst in the formation of the cumulus extracellular matrix and indispensable for female fertility.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0950-1991 1477-9129
DOI:	10.1242/dev.00422