| Recurrent spontaneous abortion (RSA) refers to two or more consecutive spontaneous abortion. The incidence of the disease accounts for about1%～2%of the women of childbearing age. The causes of recurrent spontaneous abortion is very complicated. Its etiology includes many factors, such as the male and the female chromosome abnormality, uterine abnormal anatomy, endocrine and metabolic diseases, infections, anti cardiolipin antibody, antinuclear antibodies, antisperm antibody positive and so on. However, the etiology for about50%～75%RSA remains unknown, which are called Unexplained recurrent spontaneous abortion (URSA). Many studies reveals URSA is closely related to immune factors. The animal experiments of Wegmann in1993found that normal pregnancy may have a Th2phenomenon and the imbalance between Th1/Th2in human URSA research becomes a hot spot.Tim-3(T cell immunoglobulin-and mucin domain-containing a3molecule, Tim-3) was first discovered by Kuchroo laboratory in2002as a specific marker on the Thl cells surface, specially expressed on activated Thl cells surfaces. The following studies founded that Tim-3was also expressed on the innate immune cell subsets including natural killer cells, monocytes and dendritic cells. The binding of Tim-3with its endogenous ligand galectin-9specially inducced the apoptosis of Tim-3+Th1cells, and negatively regulated the immune response of Thl cells, thereby inhibited the tissue inflammation. Tim-3participates in the development of a variety of diseases which are related to Th1/Th2imbalance.The previous study found that the Tim-3mRNA of URSA patients was highly expressed on their peripheral blood mononuclear cells, suggesting that Tim-3is likely to play an important role in the pathological process of URSA. Considering that the type and function of cells in peripheral blood and maternal-fetal interface are different,and also the mRNA expression can not reflect the whole protein expression level, it is necessary to detect the Tim-3expression on the maternal-fetal interface of villous and decidua tissues in the URSA patients. The major goal of the present study is to detect the expression of Tim-3on villous and decidual tissues of the URSA patients with immunohistochemical method, which might be helpful to further clarify the pathogenesis of URSA and to provide theoretical guidance and experimental basis. The results showed that Tim-3protein is mainly located in the cytoplasm of villi trophoblast cells and form-fitting trophoblastic cells, villi interstitial and also in the cytoplasm of glandular epithelial cells of the decidual tissue and decidual stromal. The expression of Tim-3in the villous tissues and glands of decidua tissue of the URSA patients was stronger than that of the control group (P<0.05). The results suggested that Tim-3as a new immunoregulatory molecules might play an important role in immune tolerance in the maternal-fetal interface of URSA patients. However, the exact pathogenesis still need some further research.Methods1. Research subject30patients with unexplained recurrent abortion was selected as the case group in Maternal and Child health care, Linyi city from October,2011to December,2012. These patients had2times or more abortion number before, and the average age were (29.5±3.7).30normal pregnant women in the same period (gestational age6to12w) were randomly selected as control group, and the average age were (27.5±3.6), who did not have the history of spontaneous abortion and had the normal embryonic development detected by B ultrasonic.2. Methods2.1Preparation of paraffin section:with the agreement of the subjects, the fresh villous and decidual tissues were collected from the patients or healthy control pregnants who underwent complete curettage of uterine cavity or artificial abortion. The tissues were then dehydrated, transpared, paraffined, embedded and made out to paraffin section5microns thick.2.2Immunohistochemical staining:the paraffin section were baked, dewaxed, hydrated,and with immunohistochemical staining, finally after transparented, sealed, seen the express orientation of Tim-3on villious and decidual tissues of patients with URSA with the microscope, and the Tim-3relative content of villous and decidual tissues for two groups withimmune response of integral technology.2.3Statistical analysis:experimental data were analyzed with wilcoxon rank sum test by using SPSS13.0software.P<0.05was considered to be statistical significance.Results:1. The expression and distribution of Tim-3on the villous tissues:The results showed that Tim-3protein mainly was located in the cytoplasm of villi trophoblast cells and form-fitting trophoblastic cells,villi interstitial. The expression of Tim-3in the villous tissues of the USRA group was stronger than that of the control group (P<0.05).2. The expression and distribution of Tim-3on the decidual tissues:The results showed that Tim-3protein is mainly located in the cytoplasm of glandular epithelial cells of the decidual tissue and decidual stromal. The expression of Tim-3in the decidual tissues of the USRA group was stronger than that of the control group (P<0.05)Conclusion:There is high expression of Tim-3in the maternal-fetal interface of USRA patients, which suggest that Tim-3might play an important role in disrupt of the immune tolerance in the patients with unexplained recurrent spontaneous abortion in the maternal-fetal interface.Innovations and significance:1. This research first studied the expressions of Tim-3on humans villous and decidual tissues of patients with unexplained recurrent miscarriage by immunohistochemical method.2. This study provides a theoretical guidance and experimental data for the relations of Tim-3and URSA. Tim-3may becom a target molecule for the treatment of URSA, and this may provide a new treatment of URSA for later. |
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