Song Z-H, Yu H-Y, Wang P, Mao G-K, Liu W-X, Li M-N, Wang H-N, Shang Y-L, Liu C, Xu Z-L, Sun Q-Y, Li W
1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, PR China [2] University of Chinese Academy of Sciences, Beijing, PR China.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, PR China.
Cell Death Dis. 2015 Jan 15;6(1):e1589. doi: 10.1038/cddis.2014.559.
Primary ovarian insufficiency (POI) is a common cause of infertility in around 1-2% of women aged <40 years. However, the mechanisms that cause POI are still poorly understood. Here we showed that germ cell-specific knockout of an essential autophagy induction gene Atg7 led to subfertility in female mice. The subfertility of Atg7 deletion females was caused by severe ovarian follicle loss, which is very similar to human POI patients. Further investigation revealed that germ cell-specific Atg7 knockout resulted in germ cell over-loss at the neonatal transition period. In addition, our in vitro studies also demonstrated that autophagy could protect oocytes from over-loss by apoptosis in neonatal ovaries under the starvation condition. Taken together, our results uncover a new role for autophagy in the regulation of ovarian primordial follicle reservation and hint that autophagy-related genes might be potential pathogenic genes to POI of women.
原发性卵巢功能不全（POI）是40岁以下约1%-2%女性不孕的常见原因。然而，导致POI的机制仍知之甚少。在此我们表明，生殖细胞特异性敲除必需的自噬诱导基因Atg7会导致雌性小鼠生育力下降。Atg7缺失雌性小鼠的生育力下降是由严重的卵巢卵泡丢失引起的，这与人类POI患者非常相似。进一步研究发现，生殖细胞特异性Atg7敲除导致新生期过渡阶段生殖细胞过度丢失。此外，我们的体外研究还表明，自噬可以保护卵母细胞在饥饿条件下的新生卵巢中免于因凋亡而过度丢失。综上所述，我们的结果揭示了自噬在卵巢原始卵泡储备调节中的新作用，并提示自噬相关基因可能是女性POI的潜在致病基因。
