Mai Chuxian, Yamamoto Mayu, Shibahara Hiroaki, Wang Qiong, Fukui Atsushi
Reproductive Medicine Centre, Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangdong Provincial Clinical Research Center for Obstetrical and Gynecological Diseases, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510632, Guangdong, China.; Department of Obstetrics and Gynecology, School of Medicine, Hyogo Medical University, Nishinomiya, Hyogo 663-8501, Japan.
Department of Obstetrics and Gynecology, School of Medicine, Hyogo Medical University, Nishinomiya, Hyogo 663-8501, Japan.
Reprod Biomed Online. 2025 Jun;50(6):104756. doi: 10.1016/j.rbmo.2024.104756. Epub 2024 Dec 17.
Could CD16NKp46 uterine endometrial natural killer (uNK) cells serve as a predictor of pregnancy success in women with unknown recurrent reproductive failure (URRF), and what are the underlying mechanisms involved?
A prospective study involving 63 women with URRF, followed up for 2 years. After age adjustment, 17 women remained in both the pregnant and non-pregnant groups. The pregnant group was further divided into the live birth (n = 10) and miscarriage (n = 4) groups, with three women lost to follow-up. Surface antigens expressed and cytokine produced in uNK cells were analysed with multicolour flow cytometry.
Expression NKp46 uNK (P = 0.034), NKp46 uNK (P = 0.045), CD16NKp46 uNK (P = 0.026), NKp46NKG2D uNK (P = 0.004) and NKp46NKG2D uNK (P = 0.037) cells was significantly lower in the non-pregnant group compared with the pregnant group. Also, the expression of CD16NKp46 uNK cells was significantly (P = 0.040) higher in the live birth group compared with the non-pregnant group. The threshold 44.9% of CD16NKp46 uNK cells showed the largest area under the curve. Women with decreased CD16NKp46 uNK cells (<44.9%), produced significantly higher TNF-αIFN-γ in CD56 uNK (P = 0.014) and in CD56 uNK cells (P = 0.013) and significantly lower TNF-αIFN-γ in CD56 uNK (P = 0.039) and in CD56 uNK cells (P = 0.017), and had an elevated risk of failing to achieve live birth or pregnancy (OR 21.60, 95% CI 2.14 to 218.58; P = 0.004 (OR 11.20, 95% CI 2.20 to 56.93; P = 0.005).
CD16NKp46 uNK cells are a protective factor as well as an appropriate candidate for predicting pregnancy success in URRF.
CD16NKp46子宫子宫内膜自然杀伤（uNK）细胞能否作为不明原因复发性生殖失败（URRF）女性妊娠成功的预测指标，其潜在机制是什么？
一项前瞻性研究，纳入63例URRF女性，随访2年。年龄调整后，17名女性同时留在妊娠组和非妊娠组。妊娠组进一步分为活产（n = 10）和流产（n = 4）组，3名女性失访。采用多色流式细胞术分析uNK细胞表面表达的抗原和产生的细胞因子。
与妊娠组相比，非妊娠组NKp46 uNK（P = 0.034）、NKp46 uNK（P = 0.045）、CD16NKp46 uNK（P = 0.026）、NKp46NKG2D uNK（P = 0.004）和NKp46NKG2D uNK（P = 0.037）细胞的表达显著降低。此外，与非妊娠组相比，活产组CD16NKp46 uNK细胞的表达显著更高（P = 0.040）。CD16NKp46 uNK细胞阈值为44.9%时曲线下面积最大。CD16NKp46 uNK细胞减少（<44.9%）的女性，CD56 uNK（P = 0.014）和CD56 uNK细胞（P = 0.013）中TNF-αIFN-γ产生显著更高，而CD56 uNK（P = 0.039）和CD56 uNK细胞（P = 0.017）中TNF-αIFN-γ产生显著更低，且活产或妊娠失败风险升高（OR 21.60，95%CI 2.14至218.58；P = 0.004（OR 11.20，95%CI 2.20至56.93；P = 0.005）。
CD16NKp46 uNK细胞是URRF女性妊娠成功的保护因素及合适的预测指标。
