卵丘卵母细胞复合物(COC)的迁移和基质入侵能力已被证明对排卵过程很重要。在转移性癌症中,这些能力是由于蛋白酶的表达增加,然而,关于COCs中蛋白酶表达的信息有限。本研究检查了纤溶酶的COC表达,基质金属蛋白酶(MMP)和去整合素和金属蛋白酶与血小板反应蛋白基序(ADAMTS)家族成员在大鼠和人。在老鼠身上,hCG给药使Mmp2,Mmp9,Mmp13,Mmp14,Mmp16,Adamts1和蛋白酶抑制剂Timp1,Timp3和Serpine1的COC表达增加了8-12小时。这种体内蛋白酶的排卵诱导可以通过毛喉素和ampigregulin处理培养的大鼠COCs来模拟,在Mmp2,Mmp13,Mmp14,Mmp16,Mmp19,Plat中观察到增加,以及蛋白酶抑制剂Timp1、Timp3和Serpine1。排卵时大鼠COCs和颗粒细胞之间表达的比较显示,COCs中Mmp9降低,Mmp13,Mmp14,Mmp16,Adamts1,Timp1和Timp3表达增加。在人类中,在IVF检索时,卵丘和颗粒细胞之间的表达比较显示MMP1,MMP2,MMP9和ADAMTS1降低,而MMP16,TIMP1和TIMP3的表达升高。用广谱MMP抑制剂治疗扩大的大鼠COCs,GM6001,显著降低卵丘细胞的体外迁徙。这些数据提供了多种蛋白酶及其抑制剂在COC中表达的证据,并且在排卵时赋予COC的迁移表型中起重要作用。
The migratory and matrix-invading capacities of the cumulus oocyte complex (COC) have been shown to be important for the ovulatory process. In metastatic cancers, these capacities are due to increased expression of proteases, however, there is limited information on protease expression in the COCs. The present study examined COC expression of plasmins, matrix metalloproteases (MMP) and A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) family members in the rat and human. In the rat, hCG administration increased COC expression of Mmp2, Mmp9, Mmp13, Mmp14, Mmp16, Adamts1, and the protease inhibitors Timp1, Timp3 and Serpine1 by 8-12 hours. This ovulatory induction of proteases in vivo could be mimicked by forskolin and ampiregulin treatment of cultured rat COCs with increases observed in Mmp2, Mmp13, Mmp14, Mmp16, Mmp19, Plat, and the protease inhibitors Timp1, Timp3 and Serpine1. Comparison of expression between rat COCs and granulosa cells at the time of ovulation showed decreased Mmp9 and increased Mmp13, Mmp14, Mmp16, Adamts1, Timp1 and Timp3 expression in the COCs. In human, comparison of expression between cumulus and granulosa cells at the time of IVF retrieval showed decreased MMP1, MMP2, MMP9, and ADAMTS1, while expression of MMP16, TIMP1, and TIMP3 were increased. Treatment of expanding rat COCs with a broad spectrum MMP inhibitor, GM6001, significantly reduced the migration of cumulus cells in vitro. These data provide evidence that multiple proteases and their inhibitors are expressed in the COCs and play an important role in imparting the migratory phenotype of the COCs at the time of ovulation.