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A direct action for GH in improvement of oocyte quality in poor-responder patients

机译:生长激素对不良反应患者的卵母细胞质量改善的直接作用

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Declining female fecundity at later age and the increasing tendency for women to delay childbirth have lead to a drastic rise in the number of women seeking assisted reproductive technology. Many women fail to respond adequately to standard ovarian stimulation regimens, raising a significant therapeutic challenge. Recently, we have demonstrated that the administration of GH, as an adjunct to ovarian stimulation, has improved the clinical outcomes by enhancing the oocyte quality. However, the mechanism(s) by which GH facilitated this improvement is yet to be understood. This study aimed to determine these potential mechanism(s) through the use of immunofluorescent localisation of GH receptors (GHRs) on the human oocyte and unbiased computer-based quantification to assess and compare oocyte quality between women of varying ages, with or without GH treatment. This study demonstrates for the first time, the presence of GHRs on the human oocyte. The oocytes retrieved from older women showed significant decrease in the expression of GHRs and amount of functional mitochondria when compared with those from younger patients. More interestingly, when older patients were treated with GH, a significant increase in functional mitochondria was observed in their oocytes. We conclude that GH exerts a direct mode of action, enabling the improvement of oocyte quality observed in our previous study, via the upregulation of its own receptors and enhancement of mitochondrial activity. This result, together with recent observations, provides scientific evidence in support of the use of GH supplementation for the clinical management of poor ovarian response.
机译:随着年龄的增长,女性的生育力下降,妇女延迟分娩的趋势日益增加,导致寻求辅助生殖技术的妇女人数急剧增加。许多妇女无法对标准的卵巢刺激方案做出充分反应,从而引发了巨大的治疗挑战。最近,我们已经证明,作为卵巢刺激的辅助手段,GH的施用通过提高卵母细胞质量改善了临床结局。然而,GH促进这种改善的机制尚待了解。这项研究旨在通过在人卵母细胞上使用GH受体(GHR)的免疫荧光定位和无偏倚的基于计算机的定量方法来评估和比较不同年龄女性(无论是否接受GH治疗)的卵母细胞质量,从而确定这些潜在的机制。这项研究首次证明了人类卵母细胞中存在GHR。与年轻患者相比,从老年妇女那里回收的卵母细胞显示GHRs表达和功能性线粒体数量显着减少。更有趣的是,当老年患者接受GH治疗时,其卵母细胞中功能性线粒体显着增加。我们得出的结论是,GH发挥了直接的作用方式,可以通过上调自身受体和增强线粒体活性来改善我们先前研究中观察到的卵母细胞质量。该结果与最近的观察结果一起,为支持使用GH补充剂治疗卵巢反应不良的临床管理提供了科学依据。

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