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First published online 3 March 2004
doi: 10.1242/dev.01056
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1 Department of Public Health and Cell Biology, University of Rome Tor Vergata,
Rome 00133, Italy
2 Department of Immunology and Cell Biology, Mario Negri Institute for
Pharmacological Research, Milan 20157, Italy
3 Department of Genetics, Biology and Biochemistry, University of Turin, Turin
10126, Italy
4 Institute of Endocrinology, Università degli Studi di Milano, Milan
20100, Italy
5 SigmaTau SpA, Pomezia, Rome 00040, Italy
6 MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford,
Oxford OX1 3QU, UK
7 Microbiology Section, Department of Experimental Medicine and Biochemical
Sciences, University of Perugia, Perugia 05122, Italy
8 Centro IDET, Institute of General Pathology, Università degli Studi di
Milano, Milan 20100, Italy
Author for correspondence (e-mail:
mantovani{at}marionegri.it)
Accepted 22 December 2003
PTX3 is a prototypic long pentraxin that plays a non-redundant role in
innate immunity against selected pathogens and in female fertility. Here, we
report that the infertility of Ptx3–/– mice is
associated with severe abnormalities of the cumulus oophorus and failure of in
vivo, but not in vitro, oocyte fertilization. PTX3 is produced by mouse
cumulus cells during cumulus expansion and localizes in the matrix. PTX3 is
expressed in the human cumulus oophorus as well. Cumuli from
Ptx3–/– mice synthesize normal amounts of
hyaluronan (HA), but are unable to organize it in a stable matrix. Exogenous
PTX3 restores a normal cumulus phenotype. Incorporation in the matrix of
inter-
-trypsin inhibitor is normal in
Ptx3–/– cumuli. PTX3 does not interact
directly with HA, but it binds the cumulus matrix hyaladherin tumor necrosis
factor -induced protein 6 (TNFAIP6, also known as TSG6) and thereby may
form multimolecular complexes that can cross-link HA chains. Thus, PTX3 is a
structural constituent of the cumulus oophorus extracellular matrix essential
for female fertility.
Key words: Cumulus oophorus, Extracellular matrix, Fertility, Pentraxins, Mouse
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