Study On Dendritic Cells In The Endometrium And Decidua During Menstrual Cycle And Early Pregnancy

Objective: Dendritic cells (DCs) are a heterogeneous population of bone marrow-derived cells, which present at minute numbers scattered all over the body, such as skin, mucosal surface, organic stroma, et al. DCs are the most important antigen-presenting cells (APC). As a sentinel of the immune system, immature DCs (iDCs) can directly activate resting T cells and make it produce immunologic responses. Besides the capacity to produce immunologic reaction, they could be involved in immunologic tolerance. In the central tolerance, DCs located in thymus can delete auto-reactive T cells by negative selection. Recently investigations indicated that DCs play a critical role in the peripheral tolerance. Being a physiologic progress, pregnancy is looked as a successful immunologic event, in which the embryo with semi-antigen derived from father was not rejected by mother's immune system. Present study was undertaken in order to confirm that whether DCs play a pivotal role during peri-implatation period.Method:Samples of non-pregnant endometrium from 46 women of reproductive age undergoing hysterectomy for benign diseases of uterus were obtained. These specimens had not pathologic findings at surgery or histological examination. All the patients had a regular menstrual history. None had taken oral contraceptives or any other hormones in the year preceding operation. Patients using IUD were excluded from the study. To determine the phase of the menstrual cycle of the tissue, each patient's menstrual history was taken and their endometrial histology evaluated following Noye's criteria. 21 of the samples were from the proliferative phase; 25 secretory phase samples were divided into early and late secretory phases (12 and 13 cases, respectively). The decidual samples were taken from 23 women undergoing an elective surgical termination of an intact pregnancy at 7~9weeks, the gestational age and viability of all pregnancies were confirmed by ultrasound. Biopsies of endometrium and decidua were taken immediately after removal, snap-frozen in liquid nitrogen and stored at -70℃until required. Observating the tissue'morphology with HE staining, immunohistochemistry and digital image analysis were used to test the number, density and distribution. All data was analyzed using the nonparametric Kruskal-Wallis H test as whole screening for statistical significance (P<0.01). When this test yielded positive result, Mann-Whitney U test used to uncover the pairs that significantly differed from each other (P<0.01). Analysis was done using SPSS12.0.Result: Immunohistochemistry: CD14 is a marker of macrophage, it's median density is 90.1 cells/mm2 in the endometrium. There was no statistically significant the density of CD14+ cells during the phase of the cycle. The median number was not significantly changed in early pregnancy.CD68 is expressed on mature macrophages, the median density of CD68+ cells was 113.1 cells/mm2 in the endometrium. There was no statistically significant difference in proliferative, early secretory, and early pregnancy. However the CD68+ number seemed to be increased in late secretory phase.A little number of CD83+ cells in the endometrial stroma during the menstrual cycle, the median number was 6 cells/mm2. CD83+ cells were increased in number in late secretory phase compared with early secretory phase and early pregnancy. The median density of HLA-DR+ cells was 167.2 cells/mm2 in endometrium. There was no statistically significant relation between the density of HLA-DR+ cells and the menstrual cycle. However, the median density was 379.6 cells/mm2 in decidua (p<0.01).The number of DC-SIGN+ cells was relatively stable during the phases of the cycle, the median density was 58.2 cells/mm2. In early decidua, we found that the number of DC-SIGN+ cells was increased obviously and intimate contact between DC-SIGN+ cells and CD56+ uNK cells. Double-labeling of DC-SIGN with Ki-67, a marker of proliferation, indicated that the portion of proliferating DC-SIGN+ cells was less than 0.9% in endometrium. Contrastly 10.1% of the DC-SIGN+ cells coexpressed Ki-67 in early decidua. All DC-SIGN+ cells expressed HLA-DR.Conclusion:There is a different number of APCs in the endometrium of menstrual cycle phases and the early decidua. These immunocompetent cells changed in the number and distribution in different cycle phases. The cause is not understood until now, it is suggested that the level of steroid hormone might affect this status. However, these variations indicate that APCs and particularly DCs played an important immunomodulatory role during peri-implantation. Macrophages locate consistantly in the endometrium and early pregnant decidua, suggesting that it is not affected by steroid hormone and protect against infection within the uterus.CD83, a special marker of mature DC, expressed slightly during late secretory phase and early pregnancy, showed that the CD83+cells provided a Th2 cytokine predominant enviroment. The number of DC-SIGN+ cells increased significantly in early pregnancy and they are particularly prevalent in the decidual basalis where they are located near the invading trophoblast. This implicates that it plays a crucial role for maternal immune tolerance towards the fetal allograft in early prenancy.NK cells in uterus (uNK) are the major immune cell types in late secretory endometrium and early decidua, as they accumulate during early pregnancy in the area of implantation and are accompanied by trophoblast invasion. HLA-E is a non-classical MHC-I antigen expressed on the trophoblast surface. uNK cells express the inhibitory receptor CD94/NKG2A at high levels, for which HLA-E is known to be a ligand. The interaction between HLA-E and CD94/NKG2A prevents lysis of extra villous trophoblast by uNK cells.An interplay between uNK cells and DC-SIGN+ cells by intimate contact and cytokines could contribute to the successful maintain of immune microenviroment at maternal-fetal interface.