Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany; Walter-Brendel-Centre of Experimental Medicine, University Hospital, LMU Munich, Munich, Germany.
Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.
J Reprod Immunol. 2022 Feb;149:103466. doi: 10.1016/j.jri.2021.103466. Epub 2021 Dec 14.
In contrast to genetic abnormalities which are well known to be responsible for around 50 % of human miscarriages, there is very few data about epigenetic alterations in spontaneous and recurrent miscarriages (SM, RM). The aim of this study was to analyze the histone modification marks H3K9ac and H3K4me3 in SM and RM.
The abundance of histone modifications H3K4me3/H3K9ac was analyzed by western blot in frozen abortion material of SM and RM compared to a control group of legal pregnancy terminations. Further, to characterize placental tissue cells expressing H3K4me3/H3K9ac immunohistochemistry (IHC) and immunofluorescence was performed in 20 SM, 19 RM and 26 controls.
The western blot data showed a tendency to an overall reduction of H3K4me3/H3K9ac, in the placental tissue of particularly SM. Further we differentiated between syncytiotrophoblast, cytotrophoblast and decidual cells and found a significant decrease of H3K4me3 in SM in cytotrophoblast cells and syncytial stroma. In RM H3K4me3 was downregulated exclusively in the syncytiotrophoblast. H3K9ac was reduced in SM and RM in all evaluated compartments, except from the syncytiotrophoblast.
Our study showed an overall reduced histone modification of H3K4me3 and H3K9ac in the placental tissue of SM. Concerning RM, particularly the reduction of H3K9ac was detected in the placental tissue, indicating that RM group has distinct profile in epigenetic regulation. Whether these histone modifications are part of a possible pathophysiologic cascade during SM and RM or are merely indicating a defective placentation, cannot be concluded from this study.
与已知导致约 50%人类流产的遗传异常不同，自发性和复发性流产（SM、RM）中表观遗传改变的相关数据很少。本研究旨在分析 SM 和 RM 中的组蛋白修饰标记 H3K9ac 和 H3K4me3。
通过 Western blot 分析冷冻流产组织中 H3K4me3/H3K9ac 组蛋白修饰的丰度，并与合法妊娠终止的对照组进行比较。此外，通过免疫组织化学（IHC）和免疫荧光对 20 例 SM、19 例 RM 和 26 例对照组的表达 H3K4me3/H3K9ac 的胎盘组织细胞进行了特征描述。
Western blot 数据显示，H3K4me3/H3K9ac 的整体水平呈下降趋势，尤其是在 SM 的胎盘组织中。此外，我们将胎盘组织细胞分为合体滋养层、细胞滋养层和蜕膜细胞，并发现 SM 中的细胞滋养层和合体滋养层的 H3K4me3 显著减少。在 RM 中，H3K4me3 仅在合体滋养层中下调。SM 和 RM 中 H3K9ac 在所有评估的细胞中均减少，除了合体滋养层。
我们的研究表明，SM 胎盘组织中的 H3K4me3 和 H3K9ac 整体修饰减少。对于 RM，特别是在胎盘组织中检测到 H3K9ac 的减少，表明 RM 组在表观遗传调控方面具有独特的特征。这些组蛋白修饰是否是 SM 和 RM 中可能的病理生理级联的一部分，还是仅仅表明胎盘形成缺陷，不能从本研究中得出结论。
