Activation of dormant follicles: a new treatment for premature ovarian failure?
Activation of dormant follicles: a new treatment for premature ovarian failure?
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DOI：
10.1097/gco.0000000000000268
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发表时间：
2016-06
影响因子：
2.1
通讯作者：
Hsueh AJ
中科院分区：
文献类型：
--
作者：
Kawamura K;Kawamura N;Hsueh AJ
卵巢早衰（POF）是指40岁以前闭经。由于卵巢早衰的卵泡枯竭，卵子捐赠是唯一的选择。POF患者虽然月经周期停止，但仍有部分患者卵巢内残留有休眠卵泡。最近，我们开发了一种新的不孕症治疗方法，并将其命名为体外激活（IVA），它使POF患者能够通过激活剩余的休眠卵泡来使用自己的卵子受孕。在这里，我们总结的数据显示，IVA作为一种新的不孕治疗POF患者的潜力。转基因小鼠研究表明，磷脂酰肌醇-3-激酶-AKT-叉头盒O3通路的刺激激活休眠的原始卵泡。在小鼠和人类卵巢中，磷酸酶和张力蛋白同源物抑制剂和磷脂酰肌醇-3-激酶激活剂被证明在体外培养中激活休眠的原始卵泡。随后的研究表明，卵巢碎裂抑制了Hippo信号通路，导致卵泡生长。在卵巢早衰患者中报告了将这两种方法结合在IVA方法中，然后进行卵巢组织自体移植，成功的卵泡生长和妊娠。目前，有两名健康的婴儿出生，另外还有两名孕妇怀孕。IVA治疗是一种潜在的不孕治疗POF患者有残留卵泡。
Premature ovarian failure (POF) is diagnosed by amenorrhea before 40 years of age. Owing to exhaustion of follicles in POF ovaries, egg donation is the only option. Although menstrual cycles cease in POF patients, some of them still contain residual dormant follicles in ovaries. Recently, we developed a new infertility treatment and named it as in-vitro activation (IVA), which enables POF patients to conceive using their own eggs by activation of residual dormant follicles. Here, we summarize data showing the potential of IVA as a new infertility treatment for POF patients. Transgenic mouse studies revealed that the stimulation of phosphatidylinositol-3-kinase-AKT-forkhead box O3 pathway activated dormant primordial follicles. In murine and human ovaries, the phosphatase and tensin homolog inhibitors and phosphatidylinositol-3-kinase activators were demonstrated to activate dormant primordial follicles in in-vitro cultures. Subsequent studies showed that ovarian fragmentation suppressed Hippo signaling pathway, leading to ovarian follicle growth. Combining these two methods in an IVA approach followed by ovarian tissue autotransplantation, successful follicle growth, and pregnancies were reported in POF patients. Currently, two healthy babies were delivered, together with two additional pregnancies. IVA treatment is a potential infertility therapy for POF patients who have residual follicles.