Lyzikova Yulia Anatolievna, Zinovkin Dmitry Aleksandrovich, Pranjol Md Zahidul Islam
Department of Obstetrics and Gynecology, Gomel State Medical University, Gomel, Belarus.
Department of Pathology, Gomel State Medical University, Gomel, Belarus.
Eur J Obstet Gynecol Reprod Biol. 2020 Feb;245:121-126. doi: 10.1016/j.ejogrb.2019.12.019. Epub 2019 Dec 24.
Recurrent miscarriage (RM) is a multifactorial condition that involves frequent uterine anatomical abnormalities, parental karyotype abnormalities, and clotting disorders. We investigate the potential roles of endometrium FoxP3 Tregs and CD56+ cells (uNK cells) and endometrial expression of PGRMC1 in the development of recurrent miscarriage.
This prospective study included 102 out of 286 cases of SA patients. The cases were divided into groups with RM (+RM) and without RM (-RM). Immunohistochemistry staining was made using primary antibodies to FoxP3, CD56, and PGRMC1 in both groups. Morphometry analyses were carried out in 10 non-overlapping high power fields. Mann-Whitney U test, Fisher two-tail test, correlation analysis and relative risk (RR) were evaluated. A p < 0.05 was considered statistically significant.
An increased presence of CD56-positive (p < 0.001) and FoxP3 Treg (p = 0.0005) cells was found in the endometrium, with a reduction in PGRMC1 expression compared with -RM group (p = 0.004). A positive correlation was shown between the number of CD56-positive cells and FoxP3 cells (r = 0.55), and an inverse correlation with PGRMC1 (r = -0.35) in the + RM group. A similar observation was found in the -RM group, with a positive correlation of uNK cell number with the number of pregnancies (p < 0.001; r = 0.34). Endometrial infiltration of CD56-positive (p < 0.0001) and FoxP3 (p < 0.0001) cells revealed an increased relative risk of RM. This increased risk was also revealed in SA with a loss of PGRMC1 expression (p < 0.0001).
Our prospective study suggests, for the first time, that increased endometrial infiltration of uNK, FoxP3 Treg cells and a decreased PGRMC1 expression may play potential roles in the development of RM.
复发性流产（RM）是一种多因素疾病，涉及频繁的子宫解剖异常、父母染色体核型异常和凝血障碍。我们研究子宫内膜FoxP3调节性T细胞（Tregs）和CD56⁺细胞（子宫自然杀伤细胞，uNK细胞）以及PGRMC1在子宫内膜的表达在复发性流产发生发展中的潜在作用。
这项前瞻性研究纳入了286例不明原因流产（SA）患者中的102例。这些病例被分为有复发性流产（+RM）组和无复发性流产（-RM）组。两组均使用针对FoxP3、CD56和PGRMC1的一抗进行免疫组织化学染色。在10个不重叠的高倍视野中进行形态计量分析。评估曼-惠特尼U检验、费舍尔双侧检验、相关性分析和相对风险（RR）。p < 0.05被认为具有统计学意义。
与-RM组相比，子宫内膜中CD56阳性细胞（p < 0.001）和FoxP3调节性T细胞（p = 0.0005）数量增加，PGRMC1表达降低（p = 0.004）。在+RM组中，CD56阳性细胞数量与FoxP3细胞数量呈正相关（r = 0.55），与PGRMC1呈负相关（r = -0.35）。在-RM组中也观察到类似情况，uNK细胞数量与妊娠次数呈正相关（p < 0.001；r = 0.34）。CD56阳性细胞（p < 0.0001）和FoxP3细胞（p < 0.0001）的子宫内膜浸润显示复发性流产的相对风险增加。在PGRMC1表达缺失的不明原因流产中也显示出这种风险增加（p < 0.0001）。
我们的前瞻性研究首次表明，子宫内膜中uNK、FoxP3调节性T细胞浸润增加以及PGRMC1表达降低可能在复发性流产的发生发展中起潜在作用。
