Department of Obstetrics and Gynecology, University Hospital Munich, LMU Munich, Germany.
Department of Obstetrics and Gynecology, University Hospital, University of Wuerzburg, LMU Munich, Germany.
Am J Reprod Immunol. 2021 Sep;86(3):e13437. doi: 10.1111/aji.13437. Epub 2021 May 29.
Maternal immunological rejection of the semi-allogenic fetus is discussed as one of the significant factors involved in early pregnancy loss. An array of cytokines secreted by both maternal and fetal cells is involved in generating a delicate maternal immune tolerance. Interleukin-7 (IL-7) is discussed to play a key role in pro-inflammatory processes, but there is still limited insight into the pathophysiological input on placentation and embryonic development in early pregnancy loss.
Cytokine level differences were identified with quantitative real-time PCR in placental tissue from spontaneous abortions (SA) (n = 18), recurrent spontaneous abortions (RSA) (n = 15), and healthy pregnancies (n = 15) at gestational weeks 7 to 14. Protein expression of IL-7 in the decidua was investigated by immunohistochemistry. IL-7-expressing cells were identified with double-immunofluorescence.
Decidua of women with RSA expressed almost 51-times higher values of IL-7 in gene expression analysis. Immunohistochemistry identified a significant upregulation of IL-7 in the decidua of RSA specimens (p = .013) and in the decidua of women with SA (p = .004). Double-immunofluorescence confirmed decidual stroma cells as IL-7-expressing cells.
Significantly elevated IL-7 values in the decidua of spontaneous and recurrent miscarriages imply a crucial role of the cytokine in the signaling at the feto-maternal interface of the placenta. An overexpression of IL-7 could result in early pregnancy loss by inducing a pro-inflammatory environment. Proven to be valuable in other autoimmune diseases, targeting IL-7 signaling therapeutically may prove to be a very beneficial treatment option for RSA patients.
母体对胎儿的免疫排斥被认为是导致早期妊娠丢失的重要因素之一。母胎细胞分泌的一系列细胞因子参与了母体免疫耐受的产生。白细胞介素-7（IL-7）被认为在促炎过程中发挥关键作用，但对于早期妊娠丢失中胎盘形成和胚胎发育的病理生理输入仍知之甚少。
通过定量实时 PCR 比较了自发流产（SA）（n=18）、复发性自发流产（RSA）（n=15）和健康妊娠（n=15）孕妇妊娠 7-14 周时胎盘组织中的细胞因子水平差异。通过免疫组织化学法研究了蜕膜中 IL-7 的蛋白表达。通过双免疫荧光法鉴定 IL-7 表达细胞。
RSA 患者蜕膜中 IL-7 的基因表达分析几乎高出 51 倍。免疫组织化学法显示 RSA 标本蜕膜中 IL-7 表达显著上调（p=0.013），SA 患者蜕膜中 IL-7 表达也显著上调（p=0.004）。双免疫荧光法证实蜕膜基质细胞为 IL-7 表达细胞。
自发和反复流产患者蜕膜中 IL-7 值显著升高，提示该细胞因子在胎盘胎儿-母体界面的信号传导中起关键作用。IL-7 的过度表达可能通过诱导促炎环境导致早期妊娠丢失。IL-7 信号靶向治疗已被证明在其他自身免疫性疾病中具有价值，可能成为 RSA 患者非常有益的治疗选择。
