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Germ cell-specific Atg7 knockout results in primary ovarian insufficiency in female mice

机译:生殖细胞特异性Atg7敲除导致雌性小鼠原发性卵巢功能不全

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摘要

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.
机译:在40岁以下的女性中,约有1-2%的女性患有原发性卵巢功能不全(POI)。但是,引起POI的机制仍知之甚少。在这里,我们显示了必不可少的自噬诱导基因Atg7的生殖细胞特异性敲除导致雌性小鼠的亚生育力。 Atg7缺失女性的亚生育力是由严重的卵泡丢失引起的,这与人类POI患者非常相似。进一步的研究表明,生殖细胞特异的Atg7基因敲除会导致新生儿过渡期生殖细胞过度流失。此外,我们的体外研究还表明,在饥饿条件下,自噬可以保护卵母细胞免受新生儿卵巢细胞凋亡的过度损失。综上所述,我们的结果揭示了自噬在调节卵巢原始卵泡保留中的新作用,并暗示自噬相关基因可能是女性POI的潜在致病基因。

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