Hum Reprod:大数据揭示子宫内膜成熟新机制,或改善未来不孕不育的治疗

2018-10-14 风铃 生物探索

这项研究以“Endometrial receptivity revisited: endometrial transcriptome adjusted for tissue cellular heterogeneity”为题发表在生殖医学领域的权威期刊《Human Reproduction》上。

这项研究以“Endometrial receptivity revisited: endometrial transcriptome adjusted for tissue cellular heterogeneity”为题发表在生殖医学领域的权威期刊《Human Reproduction》上。


https://doi.org/10.1093/humrep/dey301

据数据统计,2017年,在爱沙尼亚进行的2800多例体外受精(IVF)手术中,有430名婴儿出生,仅占所有出生人口的3%。研究人员分析,IVF成功率低的原因可能是在治疗几个阶段中出现的问题所致。这当中就包括胚胎植入阶段,而这一阶段正是标志着妊娠的开始。如果胚胎在错误的时间被植入到子宫,即便是最好的胚胎也会导致妊娠失败。

女性不孕可能是由子宫内膜(the inner uterine lining) 接受性问题所引起。在自然受孕中,发育中的胚胎可以“静坐等待”直到子宫内膜成熟到接受性高峰,但在IVF治疗中,选择合适的日期移植胚胎以增加怀孕机会,显得尤为重要。目前,有不同的方法可以用来评估子宫内膜容受性,其中最精确的就是检测不同基因在子宫内膜活检中的表达模式。

通常,在IVF周期的前一个周期进行微创子宫内膜活检,子宫内膜被认为是最容易接受的。通过对特定标记基因表达模式的分析,有助于确定“在正确的时间表达正确的基因”等重要信息。

论文第一作者、塔尔图大学临床医学研究所Marina Suhorut?enko 博士表示,“众所周知,子宫内膜内包括不同的细胞类型,每种细胞类型都有其独特的基因表达谱。在女性月经周期内,子宫内膜组织中上皮细胞和基质细胞的比例各不相同,由于获取组织活检的方法和工具不同,也存在个体和技术上的差异。”


在子宫内膜组织中,上皮(E)和基质(S)细胞的比例在月经周期的早期分泌期和中期分泌期之间存在差异。这影响了子宫内膜组织样本的基因表达谱——用于选择不育治疗中胚胎移植的最佳日期。图片来源:Figure by M. Suhorut?enko

在该研究中,研究人员对35名年龄23-36岁的健康、月经周期规律的、有生育能力的志愿者进行分泌早期和中期的子宫内膜组织活检以及RNA测序分析两种方法进行差异基因表达分析。

结果显示,在子宫内膜组织中,基质细胞和上皮细胞在分泌早期的平均比例分别为65%和35%,分泌中期的平均比例则为46%和54%,与组织学评价结果吻合较好。子宫内膜组织转录组分析显示,在细胞型未调整分析中,接受性子宫内膜差异表达约26%,在活检细胞组成调整后仍保持差异表达。然而,其余74%在活检细胞组成调整后在统计学上变得不显著,这也强调了组织异质性对差异表达分析的影响。这些结果揭示了子宫内膜成熟的新机制。

Suhorut?enko 博士说道,“我们的结果表明,子宫内膜活检中上皮细胞和基质细胞比例的差异改变了全组织基因表达谱,影响了差异表达分析的结果。”

爱沙尼亚基因组中心(Estonian Genome Center)的研究员Triin Laisk博士协助了这项研究的数据分析。Laisk博士表示,过去,活检细胞成分的混杂效应很大程度上被忽视了,不仅在生殖医学领域如此。考虑到这一点,我们就可以减少随机和假阳性发现的数量,最终提高我们在不同条件下的生物学知识,以及促进新的生物标志物的发现。

这项研究的结果意义重大,有助于更好地理解从接受前子宫内膜向接受后子宫内膜转变的分子过程,进而提高辅助生殖方案的有效性和个性化。

原始出处:

Marina Suhorutshenko, Viktorija Kukushkina, Agne Velthut-Meikas, et.al. Endometrial receptivity revisited: endometrial transcriptome adjusted for tissue cellular heterogeneity. Human Reproduction, dey301, https://doi.org/10.1093/humrep/dey301

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    2018-11-01 李小猫

    学习了

    0

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    2018-10-27 李小猫

    学习了

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    2018-10-16 sunylz

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