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首页> 外文期刊>Reproduction: The official journal of the Society for the Study of Fertility >Bone morphogenetic protein 15 and fibroblast growth factor 10 enhance cumulus expansion, glucose uptake, and expression of genes in the ovulatory cascade during in vitro maturation of bovine cumulus–oocyte complexes
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Bone morphogenetic protein 15 and fibroblast growth factor 10 enhance cumulus expansion, glucose uptake, and expression of genes in the ovulatory cascade during in vitro maturation of bovine cumulus–oocyte complexes

机译:骨形态发生蛋白15和成纤维细胞生长因子10增强卵丘-卵母细胞复合物体外成熟过程中的卵丘扩展,葡萄糖摄取和排卵级联基因的表达

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Oocyte-secreted factors (OSFs) regulate differentiation of cumulus cells and are of pivotal relevance for fertility. Bone morphogenetic protein 15 (BMP15) and fibroblast growth factor 10 (FGF10) are OSFs and enhance oocyte competence by unknown mechanisms. We tested the hypothesis that BMP15 and FGF10, alone or combined in the maturation medium, enhance cumulus expansion and expression of genes in the preovulatory cascade and regulate glucose metabolism favouring hyaluronic acid production in bovine cumulus–oocyte complexes (COCs). BMP15 or FGF10 increased the percentage of fully expanded COCs, but the combination did not further stimulate it. BMP15 increased cumulus cell levels of mRNA encoding a disintegrin and metalloprotease 10 ( ADAM10 ), ADAM17 , amphiregulin ( AREG ), and epiregulin ( EREG ) at 12 h of culture and of prostaglandin (PG)-endoperoxide synthase 2 ( PTGS2 ), pentraxin 3 ( PTX3 ) and tumor necrosis factor alpha-induced protein 6 ( TNFAIP6 ( TSG6 )) at 22?h of culture. FGF10 did not alter the expression of epidermal growth factor-like factors but enhanced the mRNA expression of PTGS2 at 4?h, PTX3 at 12?h, and TNFAIP6 at 22?h. FGF10 and BMP15 stimulated glucose consumption by cumulus cells but did not affect lactate production or levels of mRNA encoding glycolytic enzymes phosphofructokinase and lactate dehydrogenase A. Each growth factor increased mRNA encoding glucosamine:fructose-6-PO_(4) transaminases, key enzymes in the hexosamine pathway leading to hyaluronic acid production, and BMP15 also stimulated hyaluronan synthase 2 ( HAS2 ) mRNA expression. This study provides evidence that BMP15 and FGF10 stimulate expansion of in vitro -matured bovine COCs by driving glucose metabolism toward hyaluronic acid production and controlling the expression of genes in the ovulatory cascade, the first acting upon ADAM10 , ADAM17 , AREG , and EREG and the second on downstream genes, particularly PTGS2 .
机译:卵母细胞分泌因子(OSF)调节卵丘细胞的分化,对生育能力具有关键意义。骨形态发生蛋白15(BMP15)和成纤维细胞生长因子10(FGF10)是OSF,并通过未知机制增强卵母细胞能力。我们测试了以下假设:BMP15和FGF10单独或在成熟培养基中结合,可增强排卵前级联反应中的卵丘扩展和基因表达,并调节葡萄糖代谢,有利于牛卵丘卵母细胞复合体(COC)中透明质酸的产生。 BMP15或FGF10增加了完全扩展的COC的百分比,但这种组合并未进一步刺激它。 BMP15在培养12小时时增加了编码整合素和金属蛋白酶10(ADAM10),ADAM17,双调蛋白(AREG)和上调蛋白(EREG)的mRNA和前列腺素(PG)-内过氧化物合酶2(PTGS2),五色蛋白3的卵丘细胞水平。 (PTX3)和肿瘤坏死因子α诱导蛋白6(TNFAIP6(TSG6))在培养22小时时。 FGF10不会改变表皮生长因子样因子的表达,但会在4?h增强PTGS2,在12?h抑制PTX3和在22?h TNFAIP6的mRNA表达。 FGF10和BMP15刺激卵丘细胞消耗葡萄糖,但不影响乳酸的产生或编码糖酵解酶磷酸果糖激酶和乳酸脱氢酶A的mRNA的水平。每种生长因子均增加了编码葡糖胺:果糖-6-PO_(4)转氨酶的mRNA的水平。己糖胺途径导致透明质酸的产生,而BMP15也刺激了透明质酸合酶2(HAS2)mRNA的表达。这项研究提供了证据,证明BMP15和FGF10通过驱动葡萄糖代谢产生透明质酸并控制排卵级联反应中基因的表达来刺激体外成熟的牛COC的扩增,第一个作用于ADAM10,ADAM17,AREG和EREG以及其次是下游基因,特别是PTGS2。

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