Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany.
Department of Pathology, LMU Munich, Marchioninistr. 27, 81377 Munich, Germany.
Int J Mol Sci. 2018 Jun 26;19(7):1872. doi: 10.3390/ijms19071872.
PPARγ belongs to the group of nuclear receptors which is expressed in the trophoblast and together with other factors is responsible for the maintenance of pregnancy. Apart from that PPARγ is also a main factor for macrophage polarization. The aim of this study was to investigate the combined expression pattern and frequency of PPARγ under physiological circumstances and in spontaneous and recurrent miscarriages in the trophoblast and in maternal macrophages of the decidua. Human placental tissues of the first trimester (15 physiologic pregnancies, 15 spontaneous abortion and 16 recurrent miscarriage placentas) were analyzed for expression of the nuclear receptor PPARγ. Expression changes were evaluated by immunohistochemistry and real time PCR (RT-PCR) in trophoblast and in maternal macrophages of the decidua. Maternal macrophages were identified by double immunofluorescence using cluster of differentiation 68 (CD68) as marker for macrophages and further characterized regarding their M1/M2 polarization status. The intermediate villous trophoblast revealed a significantly lower PPARγ expression in spontaneous and recurrent abortion. Maternal macrophages express PPARγ. Their number is significantly enhanced in the decidua of spontaneous miscarriages whereas in recurrent miscarriages maternal macrophages seem to express PPARγ only in very few cases. PPARγ is associated with an M2 polarization state that is common for decidual macrophages. The lack of PPARγ in recurrent miscarriage decidual macrophages seems to be associated with a specific inflammatory response against the fetus.
PPARγ 属于核受体家族,在滋养层中表达,与其他因子一起负责维持妊娠。此外,PPARγ 也是巨噬细胞极化的主要因素。本研究旨在探讨生理情况下、自然流产和复发性流产中 PPARγ 在滋养层和蜕膜母体巨噬细胞中的联合表达模式和频率。分析了人早孕胎盘组织(15 例生理性妊娠、15 例自然流产和 16 例复发性流产胎盘)中核受体 PPARγ 的表达。通过免疫组织化学和实时 PCR(RT-PCR)在滋养层和蜕膜母体巨噬细胞中评估表达变化。使用分化群 68(CD68)作为巨噬细胞标志物进行双重免疫荧光鉴定母体巨噬细胞,并进一步表征其 M1/M2 极化状态。中间绒毛滋养层在自然流产和复发性流产中 PPARγ 的表达明显降低。母体巨噬细胞表达 PPARγ。它们的数量在自然流产的蜕膜中显著增加,而在复发性流产中,母体巨噬细胞似乎只在极少数情况下表达 PPARγ。PPARγ 与蜕膜巨噬细胞常见的 M2 极化状态相关。复发性流产蜕膜巨噬细胞中缺乏 PPARγ 似乎与针对胎儿的特定炎症反应有关。