Research question

Do endometrial stromal cells from primary infertile patients with severe ovarian endometriosis display differential secretory profiles of inflammation-associated cytokines during the implantation window that may cause infertility?

Design

Forty-eight cytokines were measured in conditioned medium of isolated endometrial stromal cells obtained from primary infertile patients without endometriosis (control group, n = 12) or with stage IV ovarian endometriosis (ovarian endometriosis group, n = 14) using multiplex assays. Key cytokines showing differential secretory profiles were validated using Western immunoblotting. Cellular phenotypic validation was carried out in vitro by comparing proliferation and migration capacity between control (n = 6) and ovarian endometriosis (n = 7) groups.

Results

CCL3, CCL4, CCL5, CXCL10, FGF2, IFNG, IL1RN, IL5, TNFA, and VEGF could be detected only in the conditioned media of stromal cells obtained from the ovarian endometriosis group. Among other cytokines detected in the conditioned media of both groups, CCL2 (P = 0.0018), CSF3 (P = 0.0017), IL1B (P = 0.0066), IL4 (P = 0.036), IL6 (P = 0.0039) and IL13 (P = 0.036) were found to be higher, whereas the concentration of IL18 was lower (P = 0.023) in the ovarian endometriosis group. Concentrations of CCL2, IL1B, IL4 and IL13 in conditioned medium reflected significant diagnostic performance for predicting ovarian endometriosis. Cellular phenotypic validation in vitro revealed an enhanced proliferative phenotype (P = 0.046) with no change in cell migratory capacity of endometrial stromal cells from the ovarian endometriosis group.

Conclusions

Endometrial stromal cells derived from severe ovarian endometriosis samples displayed a hyperinflammatory and hyperproliferative bias in the endometrial stroma during the ‘window of implantation’ putatively causing loss of fecundability.

中文翻译：

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严重卵巢子宫内膜异位症期间的子宫内膜基质细胞炎症表型作为子宫内膜异位症相关不孕症的原因。

研究问题

患有严重卵巢子宫内膜异位症的原发性不育患者的子宫内膜基质细胞在可能导致不孕的着床窗口期间是否显示出炎症相关细胞因子的不同分泌谱？

设计

 使用多重测定法在无子宫内膜异位症（对照组，n  = 12）或 IV 期卵巢子宫内膜异位症（卵巢子宫内膜异位症组，n = 14）的原发性不育患者的分离子宫内膜基质细胞的条件培养基中测量了 48 种细胞因子。使用蛋白质免疫印迹验证显示不同分泌谱的关键细胞因子。通过比较对照组 ( n  = 6) 和卵巢子宫内膜异位症 ( n  = 7) 组之间的增殖和迁移能力，在体外进行细胞表型验证。

结果

CCL3、CCL4、CCL5、CXCL10、FGF2、IFNG、IL1RN、IL5、TNFA 和 VEGF 只能在从卵巢子宫内膜异位症组获得的基质细胞的条件培养基中检测到。在两组条件培养基中检测到的其他细胞因子中，CCL2 ( P  = 0.0018)、CSF3 ( P  = 0.0017)、 IL1B ( P  = 0.0066)、 IL4 ( P  = 0.036)、 IL6 ( P  = 0.0039) 和 IL13 ( P  = 0.036）被发现更高，而 卵巢子宫内膜异位症组的 IL18 浓度较低（P = 0.023）。CCL2、IL1B、IL4 和 IL13 在条件培养基中的浓度反映了预测卵巢子宫内膜异位症的显着诊断性能。细胞表型验证体外显示增强的增殖表型（P  = 0.046），卵巢子宫内膜异位症组的子宫内膜基质细胞的细胞迁移能力没有变化。

结论

来自严重卵巢子宫内膜异位症样本的子宫内膜基质细胞在“着床窗口”期间在子宫内膜基质中显示出过度炎症和过度增殖的倾向，这可能导致生育能力丧失。