Oocytes and hypoxanthine orchestrate the G2-M switch mechanism in ovarian granulosa cells
Oocytes and hypoxanthine orchestrate the G2-M switch mechanism in ovarian granulosa cells
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卵母细胞和次黄嘌呤协调卵巢颗粒细胞中的 G2-M 转换机制
DOI：
10.1242/dev.184838
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发表时间：
2020-07-01
期刊：
影响因子：
4.6
通讯作者：
Liu, Honglin
中科院分区：
文献类型：
--
作者：
Li, Chengyu;Meng, Xueqin;Liu, Honglin
在哺乳动物生长的卵泡中。卵母细胞停滞在双线期（类似于有丝分裂中的G2/M边界），而颗粒细胞（GC）在卵泡发育期间继续增殖，反映了卵母细胞和GC之间的细胞周期重叠。次黄嘌呤（Hx），一种存在于卵泡液中的嘌呤，已被证明可诱导卵母细胞减数分裂阻滞，但其在GC增殖中的作用仍不明确。在这里，我们证明了Hx不加选择地阻止猪GC中的G2-至-M相变。然而，卵母细胞衍生的旁分泌因子（ODPF），特别是GDF 9和BMP 15，部分地通过激活ERK 1/2信号传导并使被Hx抑制的G2/M转变成为可能来维持GC的增殖。很有趣。GDF 9/BMP 15受体表达较低的GC似乎对Hx诱导的G2/M期阻滞更敏感，并且容易从卵泡壁分离。重要的是，Hx介导的G2/M进展抑制引发GC凋亡，其在GDF 9和/或BMP 15存在下得到改善。因此，我们的数据表明，卵泡内因子的平衡，特别是Hx和卵母细胞衍生的GDF 9/BMP 15，通过调节GC的细胞周期进程微调猪卵泡的发育。
In mammalian growing follicles. oocytes are arrested at the diplotene stage (which resembles the G2/M boundary in mitosis), while the granulosa cells (GCs) continue to proliferate during follicular development, reflecting a cell cycle asynchrony between oocytes and GCs. Hypoxanthine (Hx), a purine present in the follicular fluid, has been shown to induce oocytes meiotic arrest, although its role in GC proliferation remains ill-defined. Here, we demonstrate that Hx indiscriminately prevents G2-to-M phase transition in porcine GCs. However, oocyte-derived paracrine factors (ODPFs), particularly GDF9 and BMP15, maintain the proliferation of GCs, partly by activating the ERK1/2 signaling and enabling the G2/M transition that is suppressed by Hx. Interestingly. GCs with lower expression of GDF9/BMP15 receptors appear to be more sensitive to Hx-induced G2/M arrest and become easily detached from the follicular wall. Importantly, Hx-mediated inhibition of G2/M progression instigates GC apoptosis, which is ameliorated in the presence of GDF9 and/or BMP15. Therefore, our data indicate that the counterbalance of intrafollicular factors, particularly Hx and oocyte-derived GDF9/BMP15, fine-tunes the development of porcine follicles by regulating the cell cycle progression of GCs.