Starvation at birth impairs germ cell cyst breakdown and increases autophagy and apoptosis in mouse oocytes.
Starvation at birth impairs germ cell cyst breakdown and increases autophagy and apoptosis in mouse oocytes.
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出生时饥饿会损害生殖细胞囊肿的破裂并增加小鼠卵母细胞的自噬和凋亡
DOI：
10.1038/cddis.2017.3
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发表时间：
2017-02-09
影响因子：
9
通讯作者：
Shen W
中科院分区：
文献类型：
--
作者：
Wang YY;Sun YC;Sun XF;Cheng SF;Li B;Zhang XF;De Felici M;Shen W
雌性生殖寿命主要取决于原始卵泡池的大小，原始卵泡池是在出生时生殖细胞囊肿破裂后建立的。几乎三分之二的卵母细胞在生殖细胞包囊破裂过程中丢失，遵循自噬和凋亡机制。为了探讨生殖细胞包囊破裂与营养供应之间的可能关系，我们在出生时建立了小鼠幼仔饥饿模型，并评估了营养剥夺期间包囊破裂的动态。我们的研究结果表明，在饥饿36小时之间的1.5和3 dpp，在系统和卵巢水平的代谢指标显着改变，生殖细胞囊肿破裂显着减少。我们还发现，氧化应激，自噬和细胞凋亡的标志物增加，更高数量的卵母细胞在囊肿显示自噬标志物和TUNEL阳性卵母细胞和体细胞存在于卵巢饥饿的幼崽。此外，在这些卵巢中，前颗粒细胞的增殖和卵母细胞特异性转录因子Nobox的表达降低。最后，我们观察到饥饿幼仔的卵巢在重新喂食约3周后可以恢复正常数量的卵泡。总之，这些数据表明，出生时营养缺乏可以在卵巢中产生许多适应性代谢和氧化反应，导致体细胞和卵母细胞的凋亡增加，主要是在这些卵母细胞中的自噬，并导致生殖细胞囊肿破裂和卵泡组装的延迟。
The female reproductive lifespan is largely determined by the size of primordial follicle pool, which is established following germ cell cyst breakdown around birth. Almost two-third of oocytes are lost during germ cell cysts breakdown, following autophagic and apoptosis mechanisms. To investigate a possible relationship between germ cell cyst breakdown and nutrition supply, we established a starvation model in mouse pups at birth and evaluated the dynamics of cyst breakdown during nutrient deprivation. Our results showed that after 36 h of starvation between 1.5 and 3 dpp, indicators of metabolism both at systemic and ovarian level were significantly altered and the germ cell cyst breakdown markedly decreased. We also found that markers of oxidative stress, autophagy and apoptosis were increased and higher number of oocytes in cyst showing autophagic markers and of TUNEL-positive oocytes and somatic cells were present in the ovaries of starved pups. Moreover, the proliferation of pre-granulosa cells and the expression of the oocyte-specific transcription factor Nobox were decreased in such ovaries. Finally, we observed that the ovaries of the starved pups could recover a normal number of follicles after about 3 weeks from re-feeding. In conclusion, these data indicate that nutrient deficiency at birth can generate a number of adaptive metabolic and oxidative responses in the ovaries causing increased apoptosis both in the somatic cells and oocyte and autophagy mainly in these latter and leading to a delay of germ cell cyst breakdown and follicle assembly.