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衰老作为人子宫内膜基质细胞增殖和蜕膜化的调节剂:在着床中有作用吗?

Ageing, a modulator of human endometrial stromal cell proliferation and decidualization: a role for implantation?

机构信息

University of Crete, School of Medicine, Department of Obstetrics and Gynecology, Laboratory of Human Reproduction, Heraklion, Greece.

University of Crete, School of Medicine, Department of Obstetrics and Gynecology, Laboratory of Human Reproduction, Heraklion, Greece; Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, Brussels 1090, Belgium.

出版信息

Reprod Biomed Online. 2022 Aug;45(2):202-210. doi: 10.1016/j.rbmo.2022.03.028. Epub 2022 Apr 10.

DOI:10.1016/j.rbmo.2022.03.028
PMID:35773140
Abstract

RESEARCH QUESTION

Does ageing affect endometrial stromal cell function and gene expression involved in decidualization?

DESIGN

Stromal cells were isolated and cultured (98% purity) from pipelle endometrial biopsies obtained from female donors, at the proliferative phase of the menstrual cycle. Initially, 28 samples were collected (age range 25-46 years). These samples were divided into two groups: 25-35 years and 36-46 years. Cell proliferation assays were carried out to determine changes in stromal cell proliferation, in vitro, between the two groups. In addition, mRNA and protein expression of decidualization factors, BMP2 and STAT3, were analysed for the same age groups and samples using real-time polymerase chain reaction and western blot analysis, respectively. Finally, another 12 pipelle endometrial biopsies (age range 25-46 years) were used in separate in-vitro decidualization experiments. The mRNA expression of decidualization markers, prolactin and IGFBP-1 were analysed in cultured stromal cells after adding 8-bromo-cAMP.

RESULTS

A statistically significant decrease was observed in stromal cell proliferation with increasing age (P = 0.0006). Messenger RNA expression of BMP2 and STAT3 were found to decrease (P = 0.0167; P = 0.0037, respectively) in the older age group. In addition, BMP2 and STAT3 protein expression between the samples analysed changed significantly (P = 0.0085; P = 0.0463, respectively) with increasing age. In-vitro induced decidualization experiments showed significant changes in stromal cell mRNA expression of decidualization markers (IGFBP1 and prolactin) between different age groups.

CONCLUSION

Ageing affected endometrial cell function and gene expression. Changes in cell function and expression of associated molecules that differ in the ageing endometrium can help understand the causes of infertility.

摘要

研究问题

衰老是否会影响参与蜕膜化的子宫内膜基质细胞功能和基因表达?

设计

从女性供体的增殖期经阴道超声子宫内膜吸取活检中分离和培养(纯度 98%)基质细胞。最初收集了 28 个样本(年龄范围 25-46 岁)。这些样本分为两组:25-35 岁和 36-46 岁。进行细胞增殖测定以确定两组之间体外基质细胞增殖的变化。此外,使用实时聚合酶链反应和蛋白质印迹分析分别分析了相同年龄组和样本的蜕膜化因子 BMP2 和 STAT3 的 mRNA 和蛋白表达。最后,在单独的体外蜕膜化实验中使用了另外 12 个经阴道超声子宫内膜吸取活检(年龄范围 25-46 岁)。在添加 8-溴-cAMP 后,分析培养的基质细胞中蜕膜化标志物催乳素和 IGFBP-1 的 mRNA 表达。

结果

随着年龄的增长,基质细胞增殖呈统计学显著下降(P=0.0006)。发现 BMP2 和 STAT3 的信使 RNA 表达在年龄较大的组中降低(P=0.0167;P=0.0037,分别)。此外,随着年龄的增长,分析的样本之间的 BMP2 和 STAT3 蛋白表达也发生了显著变化(P=0.0085;P=0.0463,分别)。体外诱导的蜕膜化实验显示,不同年龄组基质细胞蜕膜化标志物(IGFBP1 和催乳素)的 mRNA 表达存在显著变化。

结论

衰老影响子宫内膜细胞功能和基因表达。在衰老的子宫内膜中,细胞功能和相关分子表达的变化有助于理解不孕的原因。

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