Oocyte‐secreted factor TGFB2 enables mouse cumulus cell expansion in vitro
Oocyte‐secreted factor TGFB2 enables mouse cumulus cell expansion in vitro
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DOI：
10.1002/mrd.23646
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发表时间：
2022-09
影响因子：
2.5
通讯作者：
Xiaoqiong Hao;Feifei Yuan;Yanying Cui;Meijia Zhang
中科院分区：
文献类型：
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作者：
Xiaoqiong Hao;Feifei Yuan;Yanying Cui;Meijia Zhang
卵丘扩张是从卵巢释放可受精卵母细胞所必需的，这对哺乳动物的正常受精至关重要。卵丘扩张需要表皮生长因子（EGF）样生长因子和卵母细胞旁分泌因子之间的合作。生长分化因子9（GDF 9）和骨形态发生蛋白15（BMP 15）是众所周知的由卵母细胞分泌的旁分泌因子。此外，转化生长因子-β2（TGFB 2）主要在卵母细胞中表达，其膜受体1型受体（TGFBR 1）和2型受体（TGFBR 2）位于卵丘细胞中。在我们目前的研究中，TGFB 2诱导卵母细胞切除（OOX）复合物的扩增，并在EGF存在下增加扩增相关基因的表达，表明TGFB 2使卵丘扩增。用SD 208抑制TGF-β信号传导阻断了TGF β 2促进的卵丘扩张。此外，在来自颗粒细胞中Tgfbr 2特异性耗竭的小鼠的OOX复合物的培养中，TGFB 2促进的卵丘扩增和扩增相关基因的表达受损。这些结果表明，TGFB 2可以通过TGFBR-SMAD 2/3信号传导诱导卵丘扩张。使用Zp 3-Cre小鼠的卵母细胞中的Tgfb 2特异性消耗对体内卵丘扩增没有影响，可能是由于其他卵丘扩增使能因子的代偿作用。总之，TGFB 2参与了扩展相关的基因表达和随后的卵丘扩展。
Cumulus expansion is necessary for the release of a fertilizable oocyte from the ovary, which is critical for the normal fertilization of mammals. Cumulus expansion requires cooperation between epidermal growth factor (EGF)‐like growth factors and oocyte paracrine factors. Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are well‐known paracrine factors secreted by oocytes. In addition, transforming growth factor‐β2 (TGFB2) was primarily expressed in oocytes and its membrane receptors type 1 receptor (TGFBR1) and type 2 receptor (TGFBR2) were located in cumulus cells. In our present study, TGFB2 induced expansion of oocytectomized (OOX) complexes and increased the expression of expansion‐related genes in the presence of EGF, suggesting that TGFB2 enables cumulus expansion. Inhibition of TGF‐β signaling with SD208 blocked TGFB2‐promoted cumulus expansion. Furthermore, in the culture of OOX complexes from mice of Tgfbr2‐specific depletion in granulosa cells, TGFB2‐promoted cumulus expansion and the expression of expansion‐related genes were impaired. These results suggest that TGFB2 could induce cumulus expansion through TGFBR‐SMAD2/3 signaling. Tgfb2‐specific depletion in oocytes using Zp3‐Cre mice had no effect on cumulus expansion in vivo, possibly due to the compensatory effect of other cumulus expansion‐enabling factors. Taken together, TGFB2 is involved in expansion‐related gene expression and consequent cumulus expansion.