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首页> 外文期刊>Journal of Reproductive Immunology >TGF beta 1 induces in-vitro and ex-vivo angiogenesis through VEGF production in human ovarian follicular fluid-derived granulosa cells during in-vitro fertilization cycle
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TGF beta 1 induces in-vitro and ex-vivo angiogenesis through VEGF production in human ovarian follicular fluid-derived granulosa cells during in-vitro fertilization cycle

机译：TGFβ1通过在体外施肥循环期间通过人卵巢卵泡滤液衍生的颗粒细胞VEGF生产诱导体外和前体内血管生成

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A growing body of evidence indicates that angiogenesis in folliculogenesis contributes to oocyte developmental competence in natural and in-vitro fertilization (IVF) cycle of animals. Among the known angiogenic factors, vascular endothelial growth factor (VEGF) has an important role involved in angiogenesis. However, its expression level and regulatory mechanism in ovarian follicular fluid (FF) in patients undergoing IVF with controlled ovarian stimulation (COS) remains to be explored. In this study, the primary cultured human ovarian follicular granulosa cells (GCs) were prepared from FF and their identity was characterized by the presence of the GC specific markers. The transforming growth factor beta 1 (TGF beta 1) was found to induce a significant increase in VEGF mRNA level and protein expression/secretion in GCs. In line with these observations, TGF beta 1 could be detected in the ovarian FF, ranging from about 400 to 2000 pg/mL among three IVF patient groups with different patient's serum Anti-Mullerian hormone level. The cellular signaling analysis revealed that TGF beta 1 induced VEGF production through TGF beta receptor (TGF beta R), Smad2/3, PI3 K/AKT, and JNK1/2-related signaling pathways. Finally, in a functional study, the TGF beta 1-primed GC VEGF secretion promoted in-vitro angiogenesis in vascular endothelial cells and ex-vivo vessel sprouting in aortic ring. Taken together, we demonstrated here that TGF beta 1 expressed in ovarian FF is an inducer for promoting VEGF production in follicular GCs through TGF beta R-mediated signaling pathways and the released VEGF subsequently leads to angiogenesis. This possibly contributes to oocyte developmental competence in folliculogenesis of IVF patients with a COS protocol.
机译：越来越多的证据表明，卵泡发生中的血管生成有助于动物自然和体外受精（IVF）周期中卵母细胞的发育能力。在已知的血管生成因子中，血管内皮生长因子（VEGF）在血管生成中起着重要作用。然而，在接受控制性卵巢刺激（COS）体外受精（IVF）的患者中，其在卵巢卵泡液（FF）中的表达水平和调节机制仍有待探讨。在本研究中，原代培养的人卵巢卵泡颗粒细胞（GCs）由FF制备，其特性通过GC特异性标记物的存在来表征。发现转化生长因子β1（TGFβ1）可诱导GCs中VEGF mRNA水平和蛋白质表达/分泌显著增加。与这些观察结果一致，TGF-β1可以在卵巢FF中检测到，在三个具有不同患者血清抗苗勒管激素水平的IVF患者组中，检测范围约为400到2000 pg/mL。细胞信号分析显示，TGF-β1通过TGF-β受体（TGF-βR）、Smad2/3、PI3 K/AKT和JNK1/2相关信号通路诱导VEGF生成。最后，在一项功能研究中，TGF-β1诱导的GC-VEGF分泌促进血管内皮细胞的体外血管生成和主动脉环的离体血管发芽。综上所述，我们在此证明，卵巢FF中表达的TGFβ1是通过TGFβR介导的信号通路促进卵泡GCs中VEGF生成的诱导剂，释放的VEGF随后导致血管生成。这可能有助于在COS方案的IVF患者的卵泡发育中提高卵母细胞发育能力。

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