Department of Obstetrics and Gynecology, Hebei Medical University, Shijiazhuang, Hebei, China.
Reproductive Medicine Center, The Fourth Hospital of Shijiazhuang, Gynecology and Obstetrics Hospital Affiliated to Hebei Medical University, Shijiazhuang, Hebei, China.
Am J Reprod Immunol. 2023 Dec;90(6):e13794. doi: 10.1111/aji.13794.
Whether the abnormal development of uterine natural killer (uNK) cells contributes to women with recurrent implantation failure (RIF) remains unclear.
We characterized the development of uNK cells and peripheral blood NK cells (pbNK) in the mid-luteal phase in women with RIF (n = 31) and controls (n = 14) by flow cytometry. Endometrial IL-15 mRNA expression was studied by quantitative reverse transcription-PCR. The GSE58144 dataset was used to validate the correlation results.
We found decreased proportions of stage 4 CD56+CD16-CD94+ uNK cells (median: 9.56% vs. 17.78%, P .014) and increased proportions of stage 6 CD56+CD16+CD57+ uNK cells (median: 1.54% vs. 0.74%, P = .020) in the mid-luteal endometrium of women with RIF compared to fertile women. We also found that there was no quantitative correlation between uNK cells and the corresponding pbNK cell subpopulations (P > .05). In addition, IL-15 mRNA levels in the mid-luteal endometrium were positively correlated with the proportion of CD56+ uNK cells (r = .392, P = .008), especially with stage 4 uNK cell populations (r = .408, P = .005).
We showed that the proportion of stage 4 uNK cells decreased in the RIF group compared to controls, and the decrease in stage 4 uNK cells correlated positively with low IL-15 mRNA expression. We suggest that the reduced stage 4 uNK cells in women with RIF are associated with IL-15 deficiency.
子宫自然杀伤 (uNK) 细胞的异常发育是否导致反复着床失败 (RIF) 妇女的发病机制仍不清楚。
我们通过流式细胞术描述了 RIF 患者（n = 31）和对照组（n = 14）在黄体中期 uNK 细胞和外周血 NK 细胞 (pbNK) 的发育情况。通过定量逆转录-PCR 研究了子宫内膜 IL-15 mRNA 的表达。使用 GSE58144 数据集验证了相关性结果。
我们发现 RIF 患者黄体中期子宫内膜中阶段 4 CD56+CD16-CD94+ uNK 细胞比例降低（中位数：9.56%比 17.78%，P =.014），阶段 6 CD56+CD16+CD57+ uNK 细胞比例升高（中位数：1.54%比 0.74%，P =.020）。我们还发现 uNK 细胞与相应的 pbNK 细胞亚群之间没有定量相关性（P >.05）。此外，黄体中期子宫内膜中 IL-15 mRNA 水平与 CD56+uNK 细胞比例呈正相关（r =.392，P =.008），尤其是与阶段 4 uNK 细胞群体呈正相关（r =.408，P =.005）。
与对照组相比，RIF 组中阶段 4 uNK 细胞的比例降低，阶段 4 uNK 细胞的减少与低 IL-15 mRNA 表达呈正相关。我们推测 RIF 妇女中减少的阶段 4 uNK 细胞与 IL-15 缺乏有关。
