Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility.
Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility.
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DOI：
10.1210/mend.16.6.0859
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发表时间：
2002-06
影响因子：
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通讯作者：
S. Varani;J. Elvin;Changning Yan;J. Demayo;F. DeMayo;H. Horton;M. Byrne;M. Matzuk
中科院分区：
文献类型：
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作者：
S. Varani;J. Elvin;Changning Yan;J. Demayo;F. DeMayo;H. Horton;M. Byrne;M. Matzuk
排卵过程受到内分泌和旁分泌因素的严格调节。在围排卵期，卵泡壁发生广泛的重塑，以允许卵母细胞和伴随的卵丘颗粒细胞的排出。生长分化因子 9 (GDF-9) 和骨形态发生蛋白 15 (BMP-15) 是 TGFbeta 超家族的分泌型成员，在小初级卵泡的卵母细胞中开始表达，并通过排卵表达。除了在早期卵泡发生过程中作为生长和分化因子的关键作用外，GDF-9 还充当旁分泌因子来调节排卵前卵泡中的几个关键事件。通过使用基因芯片技术分析 GDF-9 调节的表达谱，我们确定 TNF 诱导蛋白 6 (Tnfip6) 和五聚蛋白 3 (Ptx3 或 PTX3) 是 GDF-9 在排卵前卵泡颗粒细胞中诱导的新因子。 Tnfip6 在所有颗粒细胞中均由 LH 激增诱导，而在 LH 激增后，在邻近卵母细胞的卵丘颗粒细胞中特别观察到卵巢中的 Ptx3 表达。 PTX3 是分泌蛋白五聚蛋白家族的成员，在多种组织中由炎症信号诱导。为了定义排卵期间 PTX3 的功能，我们生成了缺乏 Ptx3 基因的敲除小鼠。纯合子小鼠（Ptx3(-/-)）发育正常，没有表现出任何明显的异常。 Ptx3(-/-) 雄性具有生育能力，而 Ptx3(-/-) 雌性由于卵丘细胞-卵母细胞复合物完整性缺陷而生育能力低下，这让人想起 Bmp15(-/-)Gdf9(+/-) 双突变体和 BMP IB 型受体突变小鼠。这些研究表明，PTX3 作为 GDF-9 信号转导级联的下游蛋白，在围排卵期卵丘细胞与卵母细胞相互作用中发挥着重要作用。
The ovulatory process is tightly regulated by endocrine as well as paracrine factors. In the periovulatory period, extensive remodeling of the follicle wall occurs to allow the extrusion of the oocyte and accompanying cumulus granulosa cells. Growth differentiation factor-9 (GDF-9) and bone morphogenetic protein-15 (BMP-15) are secreted members of the TGFbeta superfamily that are expressed beginning in the oocyte of small primary follicles and through ovulation. Besides its critical role as a growth and differentiation factor during early folliculogenesis, GDF-9 also acts as a paracrine factor to regulate several key events in preovulatory follicles. By analyzing GDF-9-regulated expression profiles using gene chip technology, we identified TNF-induced protein 6 (Tnfip6) and pentraxin 3 (Ptx3 or PTX3) as novel factors induced by GDF-9 in granulosa cells of preovulatory follicles. Whereas Tnfip6 is induced in all granulosa cells by the LH surge, Ptx3 expression in the ovary is specifically observed after the LH surge in the cumulus granulosa cells adjacent to the oocyte. PTX3 is a member of the pentraxin family of secreted proteins, induced in several tissues by inflammatory signals. To define PTX3 function during ovulation, we generated knockout mice lacking the Ptx3 gene. Homozygous null (Ptx3(-/-)) mice develop normally and do not show any gross abnormalities. Whereas Ptx3(-/-) males are fertile, Ptx3(-/-) females are subfertile due to defects in the integrity of the cumulus cell-oocyte complex that are reminiscent of Bmp15(-/-)Gdf9(+/-) double mutant and BMP type IB receptor mutant mice. These studies demonstrate that PTX3 plays important roles in cumulus cell-oocyte interaction in the periovulatory period as a downstream protein in the GDF-9 signal transduction cascade.