Increase in FoxP3, CD56 immune cells and decrease in glands PGRMC1 expression in the endometrium are associated with...

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.