PTX3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in in vivo fertilization.
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-alpha-trypsin inhibitor is normal in Ptx3(-/-) cumuli. PTX3 does not interact directly with HA, but it binds the cumulus matrix hyaladherin tumor necrosis factor alpha-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.
Salustri
Antonietta
A
Department of Public Health and Cell Biology, University of Rome Tor Vergata, Rome 00133, Italy.
Garlanda
Cecilia
C
Hirsch
Emilio
E
De Acetis
Marika
M
Maccagno
Alessia
A
Bottazzi
Barbara
B
Doni
Andrea
A
Bastone
Antonio
A
Mantovani
Giovanna
G
Beck Peccoz
Paolo
P
Salvatori
Giovanni
G
Mahoney
David J
DJ
Day
Anthony J
AJ
Siracusa
Gregorio
G
Romani
Luigina
L
Mantovani
Alberto
A
D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D046508:Culture Techniques; D016207:Cytokines / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005298:Fertility / Q000235:genetics / Q000502:physiology*; D005306:Fertilization; D005307:Fertilization in Vitro; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009865:Oocytes / Q000166:cytology* / Q000502:physiology; D006080:Ovarian Follicle / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000378:metabolism*; D013090:Spermatocytes / Q000378:metabolism; D000099153:Pentraxins
D002097:C-Reactive Protein; D016207:Cytokines; D006820:Hyaluronic Acid; D000683:Serum Amyloid P-Component; D000099153:Pentraxins