Department of Reproductive Endocrinology, Longgang District Maternal and Child Healthcare Hospital, 6# Ailong Road, Longgang Central District, Shenzhen City, 518172, People's Republic of China.
Institute of Reproductive Immunology, College of Life Science and Technology, Jinan University, 601# Huangpu Da Dao Xi, Guangzhou City, 510632, People's Republic of China.
Reprod Biol Endocrinol. 2018 Sep 3;16(1):84. doi: 10.1186/s12958-018-0403-5.
Tyrosine kinase receptor erythropoietin-producing hepatocellular receptor A2 (EphA2) is abundant in the endometrium and plays a role in the establishment of eutopic implantation. A similar molecular mechanism may exist between uterine implantation and tubal implantation, therefore EphA2 involvement in tubal pregnancy is suspected. Due to the limited availability of human Fallopian tube specimens, EphA2 expression in human Fallopian tube epithelium remains largely unknown.
A total of 31 women with tubal pregnancy and 41 non-pregnant women with benign uterine diseases were enrolled in this study. Immunohistochemistry was used to investigate the expression pattern of EphA2 in the Fallopian tube epithelium of non-pregnant women (n = 29) and women with tubal pregnancy (n = 17). The changes of EphA2 and its activated form, phosphorylated-EphA2 (Pho-EphA2), in the Fallopian tube epithelium from non-pregnant women (n = 12) and women with tubal pregnancy (n = 14) were compared by quantitative RT-PCR and western blot assay.
EphA2 was expressed throughout the Fallopian tube epithelium, including the isthmus, the ampulla and the infundibulum. EphA2 concentration remained unchanged throughout the whole menstrual cycle, irrespective of menstrual phases and tubal regions. EphA2 mRNA in the Fallopian tube epithelium did not differ between normal women and women with tubal pregnancy (P > 0.05). With respect to the protein level, a significantly higher ratio of EphA2 over Pho-EphA2 was shown in women with tubal pregnancy (P < 0.05).
EphA2 is widely expressed in human Fallopian tube epithelium in a temporospatial-independent manner. Dysregulated EphA2 and its phosphorylation-dependent regulatory mechanism may unexpectedly enhance the cell adhesion activity of the Fallopian tube epithelial cells, leading to a mis-contact between the Fallopian tube epithelium and the embryo.
酪氨酸激酶受体促红细胞生成素产生肝细胞受体 A2（EphA2）在子宫内膜中丰富，并在建立在位植入中发挥作用。子宫植入和输卵管植入之间可能存在类似的分子机制，因此怀疑 EphA2 参与了输卵管妊娠。由于人输卵管标本的可用性有限，EphA2 在人输卵管上皮中的表达在很大程度上仍然未知。
本研究共纳入 31 例输卵管妊娠患者和 41 例非妊娠良性子宫疾病患者。免疫组织化学法用于检测 EphA2 在非妊娠妇女（n=29）和输卵管妊娠妇女（n=17）输卵管上皮中的表达模式。通过定量 RT-PCR 和 Western blot 检测非妊娠妇女（n=12）和输卵管妊娠妇女（n=14）输卵管上皮中 EphA2 及其激活形式磷酸化 EphA2（Pho-EphA2）的变化。
EphA2 在整个输卵管上皮中表达，包括峡部、壶腹部和漏斗部。EphA2 浓度在整个月经周期内保持不变，与月经阶段和输卵管区域无关。正常妇女和输卵管妊娠妇女输卵管上皮中的 EphA2 mRNA 无差异（P＞0.05）。就蛋白水平而言，输卵管妊娠妇女中 EphA2 与 Pho-EphA2 的比值明显更高（P＜0.05）。
EphA2 以时空独立的方式广泛表达于人输卵管上皮中。EphA2 的失调及其磷酸化依赖性调节机制可能会意外增强输卵管上皮细胞的细胞黏附活性，导致输卵管上皮与胚胎之间的错误接触。
