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精液免疫调节功能受损可能在不明原因复发性流产中起作用:一项体外研究的结果。

Impaired immunomodulatory effects of seminal plasma may play a role in unexplained recurrent pregnancy loss: Results of an in vitro study.

机构信息

Department of Gynaecology and Obstetrics, Leiden University Medical Center, Leiden, The Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.

Department of Gynaecology and Obstetrics, Leiden University Medical Center, Leiden, The Netherlands.

出版信息

J Reprod Immunol. 2022 Jun;151:103500. doi: 10.1016/j.jri.2022.103500. Epub 2022 Feb 19.

Abstract

BACKGROUND

Seminal plasma contains signaling molecules capable of modulating the maternal immune environment to support implantation and pregnancy. Prior studies indicated that seminal plasma induces changes in gene transcription of maternal immune cells. Reduced immune suppressive capacity may lead to pregnancy loss. The aim of this study was to investigate the immunomodulating effects of seminal plasma on T cells and monocytes in the context of recurrent pregnancy loss (RPL).

METHODS

Female T cells and monocytes were incubated with seminal plasma of 20 males in unexplained RPL couples (RPL males) and of 11 males whose partners had ongoing pregnancies (control males). The effect of seminal plasma on messenger RNA (mRNA) expression of immune cells was measured. Levels of mRNA expression were related to key signaling molecules present in the seminal plasma. Agglomerative hierarchical cluster analysis was performed on seminal plasma expression profiles and on mRNA expression profiles.

RESULTS

Expression of CD25 and anti-inflammatory IL-10 by female T cells was significantly lower after stimulation with seminal plasma of RPL males compared to control males. Female monocytes treated with seminal plasma of RPL males showed an immune activation signature of relatively elevated HLA-DR expression. Expression of these T cell and monocyte components was particularly correlated with the amounts of TGF-β and VEGF in the seminal plasma.

CONCLUSION

Our findings indicate that seminal plasma has immunomodulating properties on female immune cells compatible with the induction of a more regulatory phenotype, which may be impaired in cases of unexplained RPL.

摘要

背景

精浆中含有信号分子,能够调节母体免疫环境,支持着床和妊娠。先前的研究表明,精浆诱导母体免疫细胞的基因转录发生变化。免疫抑制能力下降可能导致妊娠丢失。本研究旨在探讨精浆在复发性妊娠丢失(RPL)背景下对 T 细胞和单核细胞的免疫调节作用。

方法

将女性 T 细胞和单核细胞与不明原因 RPL 夫妇(RPL 男性)的 20 名男性和其伴侣持续妊娠的 11 名男性(对照男性)的精浆孵育。测量精浆对免疫细胞信使 RNA(mRNA)表达的影响。mRNA 表达水平与精浆中存在的关键信号分子相关。对精浆表达谱和 mRNA 表达谱进行凝聚层次聚类分析。

结果

与对照男性相比,RPL 男性的精浆刺激后女性 T 细胞的 CD25 和抗炎性细胞因子 IL-10 表达显著降低。用 RPL 男性的精浆处理的女性单核细胞表现出相对高表达 HLA-DR 的免疫激活特征。这些 T 细胞和单核细胞成分的表达与精浆中 TGF-β 和 VEGF 的含量特别相关。

结论

我们的研究结果表明,精浆对女性免疫细胞具有免疫调节特性,可诱导更具调节表型的特性,而在不明原因的 RPL 中,这种特性可能受损。

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