Lithium treatment promotes the activation of primordial follicles through PI3K/Akt signaling†
Lithium treatment promotes the activation of primordial follicles through PI3K/Akt signaling†
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锂处理通过PI 3 K/Akt信号转导促进原始卵泡的激活
DOI：
10.1093/biolre/ioac150
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发表时间：
2022-08-08
影响因子：
3.6
通讯作者：
Zhang，Meijia
中科院分区：
文献类型：
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作者：
Li，Biao;Wang，Weiyong;Zhang，Meijia
在哺乳动物中，休眠的原始卵泡代表了整个生殖生命的卵巢储备。体外激活休眠的原始卵泡已被用于治疗卵巢功能不全（POI）患者。然而，仍然缺乏有效的策略来刺激体内卵泡激活。在这项研究中，我们使用体外卵巢培养系统和腹腔注射来研究锂处理对原始卵泡激活的影响。锂能增加小鼠卵巢中生长卵泡的数量，促进前颗粒细胞增殖。此外，锂显著增加磷酸化蛋白激酶B（Akt）水平和具有叉头盒O3 a（FOXO 3a）核输出的卵母细胞数量。LY 294002抑制磷脂酰肌醇3激酶（PI 3 K）/Akt通路逆转了锂促进的小鼠原始卵泡激活。这些结果表明锂通过PI 3 K/Akt信号通路促进小鼠原始卵泡激活。锂还促进原始卵泡激活，并增加体内小鼠卵巢和体外培养的人卵巢组织中p-Akt的水平。总之，锂通过PI 3 K/Akt信号促进小鼠和人类的原始卵泡活化。锂可能是一种潜在的口服药物，用于治疗残留休眠原始卵泡的POI患者的不孕症。
In mammals, dormant primordial follicles represent the ovarian reserve throughout reproductive life. In vitro activation of dormant primordial follicles has been used to treat patients with premature ovarian insufficiency (POI). However, there remains a lack of effective strategies to stimulate follicle activation in vivo. In this study, we used an in vitro ovarian culture system and intraperitoneal injection to study the effect of lithium treatment on primordial follicle activation. Lithium increased the number of growing follicles in cultured mouse ovaries and promoted pre-granulosa cell proliferation. Furthermore, lithium significantly increased the levels of phosphorylated protein kinase B (Akt) and the number of oocytes with forkhead Box O3a (FOXO3a) nuclear export. Inhibition of the phosphatidylinositol 3 kinase (PI3K)/Akt pathway by LY294002 reversed lithium-promoted mouse primordial follicle activation. These results suggest that lithium promotes mouse primordial follicle activation by the PI3K/Akt signaling. Lithium also promoted primordial follicle activation and increased the levels of p-Akt in mouse ovaries in vivo and in human ovarian tissue cultured in vitro. Taken together, lithium promotes primordial follicle activation in mice and humans by the PI3K/Akt signaling. Lithium might be a potential oral drug for treating infertility in POI patients with residual dormant primordial follicles.