The Expression And Significance Of VEGF And MIF In Endometrium During The Window Of Implantation Of Polycystic Ovary Syndrome

Polycystic ovarian syndrome (PCOS) is a disease caused by reproductive endocrine and metabolic disorders. It is the main reason for anovulatory infertility patients.For PCOS patients's anovulation. at present for PCOS patients,after correction of endocrine and metabolic disorders return,they can return normal ovulation, but there exist the phenomenon of low pregnancy rate and high miscarriage rate. This problem is a hot and one of the difficulties in reproductive endocrine studies at home and abroad.Most scholars believe that the phenomenon may be associated with reduction of endometrial receptivity for embryo caused by the long-term hormone imbalance.Embryo implantation and growth require the endometrium and embryo developing synchronously. It is generally believed that 7-8 days after ovulation (the 21-22 days of menstrual cycle) is the short period during which time the endometrial allow embryo implantation.This period is known as " the window of implantation". Studies suggest that there is adhesion, invasion, placenta formation three phases in the implantation of the embryo, any link going wrong will lead to embryos can not implantation, causing adverse pregnancy outcomes. Previous researches suggest that: integrin play a major role in the adhesion process of the blastocyst and endometrial; matrix metalloproteinases can degrade extracellular matrix in the endometrium so that the blastocyst invade the endometrium implantation site; leukemia inhibitory factor expresses specifically in embryo implantation phase of endometrium. They are considered to be endometrial receptivity markers. However, there is no generally accepted and precise endometrial receptivity marker.VEGF is a kind of protein which Ferrara and others separated and purified from bovine pituitary follicular cells in vitro culture medium in 1989.It distributes widely in human and animal liver, brain, kidney, lung,spleen and pituitary,bone, ovary and other tissues. It belongs heparin-binding protein family. The main biological effects of VEGF binding to its receptor is promoting inducing vascular endothelial cell division and proliferation, and promoting endothelial cell migration, enhancing vascular permeability and plasma extravasation, so that a large number of new blood vessels can generate by sprouting.VEGF binding to its receptor also make non-endothelial cells secrete VEGF, and then Effect on other cells through paracrine mechanisms. VEGF expresses in endometrium throughout the menstrual cycle, and is cycle-dependent changes. During the window of implantation, VEGF may affect embryo implantation by increasing vascular permeability of embryo implantation site, enhancing the invasive of embryo and endometrial receptivity. On the other hand, VEGF is also known as vascular permeability factor, it will make endometrial vascular system which begin to expand in the early implantation expand more significantly after implantation,and vascular permeability enhance, to prepare for the implantation.Macrophage migration inhibitory factor (MIF) is a cytokine, enzyme and neuroendocrine hormone. It is a multi-performance characteristics of protein molecule.It widely participate in inflammatory, tumor formation process, cell proliferation and immune response. Studies suggest that in normal endometrial tissue, the expression of MIF in the endometrium is cycle-dependent.It can upregulate the expression of integrins and VEGF, and it and other cytokines may also exist the mutual regulation relationship, which affect the endometrium receptivity. It may play an active role in the embryo implantation. The expression of MIF and VEGF are closely related to endometrial receptivity. This issue will use the method of immunohistochemical to determine the expressiones of MIF and VEGF in the endometrium of PCOS patients during the window of implantation,and analysis the correlation between the two,and discuss the possible mechanism of the relationship between the expression of MIF, VEGF and the phenomenon that PCOS patients still appears the low pregnancy rate and high abortion rate after endocrine disorders was corrected.Objective1 Research the expression of VEGF and MIF in the endometrial tissues of PCOS and control groups patients during the window of implantation. Discuss the correlation between VEGF,MIF and the endometrial receptivity of PCOS patients after endocrine disorders was corrected.2 Discuss the possible mechanism of VEGF,MIFand the low pregnancy rate and high abortion rate after the endocrine disorders of PCOS patients was corrected.Materials and methods1 Object of study and grouping PCOS group:10 cases married PCOS patients from November 2009 to June 2010 at the Third Affiliated Hospital of Zhengzhou University gynecology outpatient, aged 25 to 35 years, the average age (27.80±1.87) years. Inclusion criteria:the diagnosis of PCOS meet 2003 Rotterdam diagnostic criteria:①sporadic ovulation or no ovulation;②the clinical manifestations of hyperandrogenism and (or) hyperandrogenism;③ultrasound shows polycystic ovary [one or both ovaries with more than 12 follicles 2～9 mm in diameter and (or) ovarian volume greater than 10ml]; 2 in line with the 3 above-mentioned, and exclusion of other diseases, such as cushing syndrome,congenital adrenal hyperplasia, androgen secreting tumors.After treatment for 3 to 9 months,the basic endocrine becomes normal,and menstrual becomes regulate, normal ovulation in the natural cycle or after ovulation induction therapy; B-ultrasound by vaginal didn't find uterine and ovaries organic disease, and no endometriosis; husband's semen examination was normal. Control group:11 cases infertility patients due to husband's factor or tubal factor for the same period at the Third Affiliated Hospital of Zhengzhou University gynecology outpatient, aged 25 to 35 years, the average age (29.0±2.79) years. Inclusion criteria:menstrual is regulate, ovulation is normal; the basic endocrine is normal; B- ultrasound by vaginal didn't find uterine and ovaries organic disease, and no endometriosis; didn't use hormone drugs in past 3 months.PCOS and control groups have been collecting samples of patients with informed consent.2 Specimen processing and testing methods PCOS group and control group patients take fasting venous blood during 7 to 8 days after ovulation, and determine human chorionic gonadotropin (HCG) levels. It is belived that pregnancy isn't possible when HCG<30 IU/L. Take endometrium tissue using a one-time endometrial suction the day confirmed fasting venous blood HCG<30 IU/L. The Fresh endometrial tissue fixed with 10% formalin for 6-24h,then conventional dehydrated, embedded in paraffin. Each specimen were sectioned serially for 4mm. To 60℃oven for 2 hour, routine HE staining. Observe endometrial histology. Glass slides coated with poly-lysine anti-off tablet, after dewaxing, hydration, microwave antigen retrieval,the expression of MIF and VEGF were qualitative and semi quantitative determined by immunohistochemistry method.3 Statistical analysisAll data were statistically analyzed using statistical analysis SPSS17.0 software. Data were analyzed using t test and the pearson correlation analysis. Comparison of sample rate of categorical data use Fisher's exact probabilities, P<0.05 as significant difference.Results1 Comparison of the general situation for research object:compared with PCOS group and the control group, age difference is no statistically significant (P> 0.01).2 Comparison of endometrial pathology in PCOS group and control group: the rate of poor secretion response in PCOS group secretory endometrium is higher than that of control group. The difference is statistically significant (P<0.01).3 The expression of VEGF in endometrial tissues of the two groups:VEGF was mainly expressed in the cytoplasm of glandular epithelial cells, stromal cells and vascular endothelial cells, the expression of VEGF in the cytoplasm of the glandular epithelial cells was more obvious. PCOS group has lower expression than the control group. The difference is statistically significant (P<0.05).4 The expression of MIF in endometrial tissues of the two groups:MIF expressed mainly in the cytoplasm of glandular epithelial cells and stromal cells. The expression of MIF in PCOS group endometrial is lower than that of the control group.The difference is statistically significant (P<0.05.)5 The expression of MIF and VEGF in the endometrium of PCOS group has a significant positive correlation (correlation coefficient= 0.686, P<0.05).Conclusions1 The low expression of MIF and VEGF in endometrial tissue of PCOS group during the window of implantation may influence the endometrial receptivity of PCOS patients.2 The expression of MIF and VEGF in endometrial tissue of PCOS groups is positively correlated.lt tips that the Collaboration of the two lead to low pregnancy rate and high abortion rate after the endocrine disorders of PCOS patients was corrected.