CN106978472A - 人卵母细胞质量下降相关的microRNA及其应用 - Google Patents

人卵母细胞质量下降相关的microRNA及其应用 Download PDF

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CN106978472A
CN106978472A CN201610026122.7A CN201610026122A CN106978472A CN 106978472 A CN106978472 A CN 106978472A CN 201610026122 A CN201610026122 A CN 201610026122A CN 106978472 A CN106978472 A CN 106978472A
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陈薪
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Abstract

本发明涉及人卵母细胞质量下降相关的miRNA，其特征在于：所述microRNA为hsa-miR-99a、hsa-miR-99b、hsa-miR-125a、hsa-miR-450a、hsa-miR-127、hsa-miR-200c、hsa-miR-10b、hsa-miR-200b、hsa-miR-200a、hsa-miR-218、hsa-miR-429、hsa-miR-7974、hsa-miR-141、hsa-miR-27b和hsa-miR-125b。当所述microRNA均超过年轻正常女性的表达量2.5倍以上，判断为卵母细胞质量下降。可广泛应用于妇产科的孕前咨询、启动促排卵治疗指针等方面。

Description

人卵母细胞质量下降相关的 microRNA 及其应用
技术领域
本发明涉及人类卵巢衰老的诊断领域，更具体地讲，涉及人卵母细胞质量下降相关的microRNA及其应用。
背景技术
卵母细胞质量下降是指卵母细胞受精、受精后卵裂、形成囊胚、着床和继续妊娠的能力下降，主要表现为减数分裂时期纺锤体异常、染色体排列错误、端粒缩短以及黏连蛋白缺失等。卵母细胞质量下降会增加非整倍体卵母细胞的产生概率，并最终导致不孕和流产。卵母细胞质量下降的发生率随着女性年龄升高而增加，还受到环境、生活方式、疾病和医疗性等因素影响。卵母细胞质量下降，尤其是非整倍体的产生，将直接导致胎儿流产、新生儿智力和生理功能异常以及肿瘤的发生，极大影响人类的生育健康和人口素质。
随着女性因教育、工作和社会因素等原因推迟生育年龄，以及国家计划生育政策的改变，要求妊娠的高龄女性明显增多。卵母细胞质量下降是高龄女性不孕和助孕治疗反复失败的关键，目前已成为生殖医学面临的一个重大难题。
目前的生殖医学临床工作，主要是根据女性基础窦状卵泡数来决定促排卵方案，B超和性激素检查也只能监测卵泡发育的数量。由于取卵之前根本无法预知该周期的卵母细胞质量，造成相当一部分女性尤其是大部分的高龄女性，因为当周期卵母细胞质量不佳而无法获得优良胚胎，最终无法获得临床妊娠，白白耗费了患者及其家属大量的时间、精力和金钱；同时助孕治疗失败，也给患者及其家属造成了极大的精神压力。因此，在促排卵治疗前，亟需一种能预测当周期卵母细胞质量的方法，用于决定该周期是否适合启动促排卵治疗，以及后续的取卵、移植、黄体支持等一系列工作。
发明内容
本申请人针对上述问题进行研究，提供了一组与人卵母细胞质量下降相关的microRNA，用于预测当周期卵母细胞质量，为临床诊疗提供参考。
本发明所采用的技术方案如下：一组与人卵母细胞质量下降相关的microRNA，所述microRNA有15个，包括hsa-miR-99a、hsa-miR-99b、hsa-miR-125a、hsa-miR-450a、hsa-miR-127、hsa-miR-200c、hsa-miR-10b、hsa-miR-200b、hsa-miR-200a、hsa-miR-218、hsa-miR-429、hsa-miR-7974、hsa-miR-141、hsa-miR-27b和hsa-miR-125b。
上述microRNA在判断人卵母细胞质量下降中的应用：与正常质量卵母细胞的女性相比，在卵母细胞质量下降女性的颗粒细胞、卵泡液和血清中，所述microRNA的表达量明显升高，且每个microRNA的表达量均达到2.5倍以上（2.5倍-29.2倍）。根据基因互作分析，揭示所述microRNA主要与PI3K-AKT-mTOR信号通路、IGF-1受体信号通路和血管生成密切相关。
按照如下方法可筛选出满足本发明目的microRNA：（1）体外收集38岁以上女性自然衰老卵巢中获得的卵母细胞、颗粒细胞、卵泡液和血清，以及30岁以下女性正常卵巢中获得的卵母细胞、颗粒细胞、卵泡液和血清；（2）根据卵母细胞受精、卵裂、囊胚形成、着床和继续妊娠能力区分为卵母细胞质量正常组和卵母细胞质量下降组；使用深度测序方法，体外检测两组颗粒细胞和血清中microRNA全序列表达；进行表达差异分析，获得与卵母细胞质量下降相关的microRNA；（3）根据基因互作分析，揭示所述microRNA的靶基因及其作用机制，主要与PI3K-AKT-mTOR信号通路、IGF-1受体信号通路和血管生成密切相关。
本发明的有益效果如下：
使用该方法可判断卵母细胞质量是否下降。在月经周期第2天，检测血清中所述15个microRNA的表达量；如果所有值均超过年轻正常女性表达量的2.5倍以上，可判断为卵母细胞质量下降；建议取消该周期促排卵治疗，给予其他辅助性治疗或等待下一个月经周期。本发明在促排卵治疗前即可预知卵母细胞质量以决定是否启动促排卵治疗，可有效节省患者及其家属的时间、精力、治疗费用及并减少其精神压力；可广泛应用于妇产科的孕前咨询、启动促排卵治疗指针等方面。
附图说明
图1为所述microRNA的表达量在卵母细胞质量下降组与卵母细胞质量正常组的倍数。
具体实施方式
下面说明本发明的具体实施方式。
一组人卵母细胞质量下降相关的microRNA，所述microRNA有15个，包括hsa-miR-99a、hsa-miR-99b、hsa-miR-125a、hsa-miR-450a、hsa-miR-127、hsa-miR-200c、hsa-miR-10b、hsa-miR-200b、hsa-miR-200a、hsa-miR-218、hsa-miR-429、hsa-miR-7974、hsa-miR-141、hsa-miR-27b和hsa-miR-125b。在月经周期第2天，检测血清中所述15个microRNA的表达量；如果所有值均超过年轻正常女性表达量的2.5倍以上，可判断为卵母细胞质量下降；建议取消该周期促排卵治疗，给予其他辅助性治疗或等待下一个月经周期。本发明在促排卵治疗前即可预知卵母细胞质量以决定是否启动促排卵治疗，可有效节省患者及其家属的时间、精力、治疗费用及并减少其精神压力；可广泛应用于妇产科的孕前咨询、启动促排卵治疗指针等方面。
以上描述是对本发明的解释，不是对发明的限定，本发明所限定的范围参见权利要求，在不违背本发明的精神的情况下，本发明可以作任何形式的修改。

Claims (1)

1.人卵母细胞质量下降相关的miRNA，其特征在于：一组人卵母细胞质量下降相关的microRNA，所述microRNA有15个，包括hsa-miR-99a、hsa-miR-99b、hsa-miR-125a、hsa-miR-450a、hsa-miR-127、hsa-miR-200c、hsa-miR-10b、hsa-miR-200b、hsa-miR-200a、hsa-miR-218、hsa-miR-429、hsa-miR-7974、hsa-miR-141、hsa-miR-27b和hsa-miR-125b。
CN201610026122.7A 2016-01-15 2016-01-15 人卵母细胞质量下降相关的microRNA及其应用 Pending CN106978472A (zh)

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CN111560443A (zh) * 2020-06-19 2020-08-21 湖南人文科技学院 一组筛选优质猪卵母细胞的生物分子标记及其应用

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CN109182515A (zh) * 2018-09-06 2019-01-11 中山大学附属第六医院 分子标志物miR-99a的新用途
CN110038026A (zh) * 2019-03-27 2019-07-23 浙江大学 mmu-miR-218-5p在制备抑制胚胎着床的药物中的应用
CN110038026B (zh) * 2019-03-27 2021-08-17 浙江大学 mmu-miR-218-5p在制备抑制胚胎着床的药物中的应用
CN111560443A (zh) * 2020-06-19 2020-08-21 湖南人文科技学院 一组筛选优质猪卵母细胞的生物分子标记及其应用

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