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Contribution of senescence in human endometrial stromal cells during proliferative phase to embryo receptivity†.
Biology of Reproduction ( IF 3.1 ) Pub Date : 2020-04-14 , DOI: 10.1093/biolre/ioaa044
Hiroyuki Tomari 1, 2 , Teruhiko Kawamura 1 , Kazuo Asanoma 1 , Katsuko Egashira 1 , Keiko Kawamura 1 , Ko Honjo 2 , Yumi Nagata 2 , Kiyoko Kato 1
Affiliation  

Successful assisted reproductive technology pregnancy depends on the viability of embryos and endometrial receptivity. However, the literature has neglected effects of the endometrial environment during the proliferative phase on implantation success or failure. Human endometrial stromal cells (hESCs) were isolated from endometrial tissues sampled at oocyte retrieval during the proliferative phase from women undergoing infertility treatment. Primary hESC cultures were used to investigate the relationship between stemness and senescence induction in this population and embryo receptivity. Patients were classified as receptive or non-receptive based on their pregnancy diagnosis after embryo transfer. Biomarkers of cellular senescence and somatic stem cells were compared between each sample. hESCs from non-receptive patients exhibited significantly higher (P < 0.01) proportions of senescent cells, mRNA expressions of CDKN2A and CDKN1A transcripts (P < 0.01), and expressions of genes encoding the senescence-associated secretory phenotype (P < 0.05). hESCs from receptive patients had significantly higher (P < 0.01) mRNA expressions of ABCG2 and ALDH1A1 transcripts. Our findings suggest that stemness is inversely associated with senescence induction in hESCs and, by extension, that implantation failure in infertility treatment may be attributable to a combination of senescence promotion and disruption of this maintenance function in this population during the proliferative phase of the menstrual cycle. This is a promising step towards potentially improving the embryo receptivity of endometrium. The specific mechanism by which implantation failure is prefigured by a loss of stemness among endometrial stem cells, and cellular senescence induction among hESCs, should be elucidated in detail in the future.

中文翻译:

增殖期人类子宫内膜基质细胞衰老对胚胎容受性的贡献†。

成功的辅助生殖技术妊娠取决于胚胎的活力和子宫内膜的容受性。然而,文献忽略了增殖期子宫内膜环境对植入成功或失败的影响。人类子宫内膜基质细胞 (hESCs) 是从接受不孕症治疗的女性增殖期取卵时采集的子宫内膜组织中分离出来的。原代 hESC 培养物用于研究该群体中干性和衰老诱导与胚胎接受性之间的关系。患者被分类为接受不接受根据他们在胚胎移植后的妊娠诊断。在每个样品之​​间比较细胞衰老和体细胞干细胞的生物标志物。来自未接受患者的 hESC 表现出显着更高 ( P  < 0.01) 比例的衰老细胞、CDKN2ACDKN1A转录本的mRNA 表达( P  < 0.01) 以及编码衰老相关分泌表型的基因表达 ( P  < 0.05)。接受患者的hESCs ABCG2ALDH1A1  mRNA表达显着升高(P < 0.01)成绩单。我们的研究结果表明,干性与 hESC 中的衰老诱导呈负相关,并且,不孕症治疗中的植入失败可能归因于在月经周期的增殖阶段该人群中衰老促进和这种维持功能的破坏的组合. 这是朝着潜在改善子宫内膜的胚胎容受性迈出的有希望的一步。子宫内膜干细胞干性丧失和 hESC 细胞衰老诱导预示着床失败的具体机制,应在未来详细阐明。
更新日期:2020-04-14
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