PTX3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in in vivo fertilization

PTX3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in in vivo fertilization
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DOI:
10.1242/dev.01056
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发表时间:
2004-04-01
期刊:
影响因子:
4.6
通讯作者:
Mantovani, A
Mantovani, A
中科院分区:
生物学2区
文献类型:
--
作者:
Salustri, A;Garlanda, C;Mantovani, A

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PTX 3是一种原型长五聚蛋白,在针对选定病原体的先天免疫和女性生育力中发挥非冗余作用。在这里,我们报告,Ptx 3(-/-)小鼠的不育症与严重异常的卵丘和失败的体内,但不是在体外,卵母细胞受精。PTX 3由小鼠卵丘细胞在卵丘扩张期间产生并定位于基质中。PTX 3也在人卵丘中表达。来自Ptx 3(-/-)小鼠的累积物合成正常量的透明质酸(HA),但不能将其组织成稳定的基质。外源性PTX 3恢复正常的卵丘表型。在Ptx 3(-/-)堆积物中,间-α-胰蛋白酶抑制剂的基质中的掺入是正常的。PTX 3不直接与HA相互作用,但它结合卵丘基质透明质酸肿瘤坏死因子α诱导的蛋白6(TNFAIP 6,也称为TSG 6),从而可能形成可交联HA链的多分子复合物。因此,PTX 3是女性生育力所必需的卵丘细胞外基质的结构成分。
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-a-trypsin inhibitor is normal in Ptx3(-/-) cumuli. PTX3 does not interact directly with HA, but it binds the cumulus matrix hyaladherin tumor necrosis factor a-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.