Wang Yong-Yong, Sun Yuan-Chao, Sun Xiao-Feng, Cheng Shun-Feng, Li Bo, Zhang Xi-Feng, De Felici Massimo, Shen Wei
College of Life Sciences, Qingdao Agricultural University, Qingdao 266109, China.
College of Animal Science and Technology, Institute of Reproductive Sciences, Qingdao Agricultural University, Qingdao 266109, China.
Cell Death Dis. 2017 Feb 9;8(2):e2613. doi: 10.1038/cddis.2017.3.
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 d.p.p., 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.
女性的生殖寿命在很大程度上取决于原始卵泡池的大小，原始卵泡池是在出生前后生殖细胞囊肿破裂后形成的。在生殖细胞囊肿破裂过程中，近三分之二的卵母细胞会通过自噬和凋亡机制丢失。为了研究生殖细胞囊肿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崽饥饿模型，并评估了营养剥夺期间囊肿破裂的动态变化。我们的结果表明，在出生后1.5至3天之间饥饿36小时后，全身和卵巢水平的代谢指标均发生了显著变化，生殖细胞囊肿破裂明显减少。我们还发现，氧化应激、自噬和凋亡的标志物增加，饥饿幼崽的卵巢中，囊肿内显示自噬标志物的卵母细胞、TUNEL阳性卵母细胞和体细胞数量增多。此外，此类卵巢中颗粒前体细胞的增殖和卵母细胞特异性转录因子Nobox的表达均降低。最后，我们观察到，饥饿幼崽的卵巢在重新喂食约3周后可恢复正常数量的卵泡。总之，这些数据表明，出生时的营养缺乏会在卵巢中引发一系列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，主要是后者的自噬增加，并导致生殖细胞囊肿破裂和卵泡组装延迟。
