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.
Department of Public Health and Cell Biology, University of Rome Tor Vergata, Rome 00133, Italy.
Antonietta
A
Salustri
Cecilia
C
Garlanda
Emilio
E
Hirsch
Marika
M
De Acetis
Alessia
A
Maccagno
Barbara
B
Bottazzi
Andrea
A
Doni
Antonio
A
Bastone
Giovanna
G
Mantovani
Paolo
P
Beck Peccoz
Giovanni
G
Salvatori
David J
DJ
Mahoney
Anthony J
AJ
Day
Gregorio
G
Siracusa
Luigina
L
Romani
Alberto
A
Mantovani
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