Ectopic pregnancy is the major cause of maternal morbidity and mortality in the first trimester of pregnancy. Tubal ectopic pregnancy (TEP) accounts for nearly 98% of all ectopic pregnancies. TEP is usually associated with salpingitis but the underlying mechanism in salpingitis leading to TEP remains unclear. Adrenomedullin (ADM) is a peptide hormone abundantly expressed in the fallopian tube with potent anti-inflammatory activities. Its expression peaks at the early luteal phase when the developing embryo is being transported through the fallopian tube. In the present study, we demonstrated reduced expression of ADM in fallopian tubes of patients with salpingitis and TEP. Using macrophages isolated from the fallopian tubes of these women, our data revealed that the salpingistis-associated ADM reduction contributed to aggravated pro-inflammatory responses of the tubal macrophages resulting in production of pro-inflammatory and pro-implantation cytokines IL-6 and IL-8. These cytokines activated the expression of implantation-associated molecules and Wnt signaling pathway predisposing the tubal epithelium to an adhesive and receptive state for embryo implantation. In conclusion, this study provided evidence for the role of ADM in the pathogenesis of TEP through regulating the functions of tubal macrophages.

异位妊娠是孕早期孕产妇发病率和死亡率的主要原因。输卵管异位妊娠 (TEP) 占所有异位妊娠的近 98%。TEP 通常与输卵管炎有关，但输卵管炎导致 TEP 的潜在机制仍不清楚。肾上腺髓质素 (ADM) 是一种肽类激素，在输卵管中大量表达，具有强大的抗炎活性。当发育中的胚胎通过输卵管运输时，它的表达在黄体早期达到峰值。在本研究中，我们证明了输卵管炎和 TEP 患者输卵管中 ADM 的表达降低。使用从这些女性的输卵管中分离出的巨噬细胞，我们的数据显示，输卵管炎相关的 ADM 减少导致输卵管巨噬细胞的促炎反应加剧，导致促炎和促着床细胞因子 IL-6 和 IL-8 的产生。这些细胞因子激活植入相关分子和 Wnt 信号通路的表达，使输卵管上皮细胞处于粘附和接受状态以进行胚胎植入。总之，本研究通过调节输卵管巨噬细胞的功能，为ADM在TEP发病机制中的作用提供了证据。这些细胞因子激活植入相关分子和 Wnt 信号通路的表达，使输卵管上皮细胞处于粘附和接受状态以进行胚胎植入。总之，本研究通过调节输卵管巨噬细胞的功能，为ADM在TEP发病机制中的作用提供了证据。这些细胞因子激活植入相关分子和 Wnt 信号通路的表达，使输卵管上皮细胞处于粘附和接受状态以进行胚胎植入。总之，本研究通过调节输卵管巨噬细胞的功能，为ADM在TEP发病机制中的作用提供了证据。