Expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in human endometrium of unexplained infertility
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Objective To study the expression of matrix metalloproteinase-9(MMP-9) and tissue inhibitor of metalloproteinase-1 protein(TIMP-1) in cycling endometrium with unexplained infertility and normal endometrium,and to explore the relationship between the expression of MMP-9,TIMP-1 in unexplained infertility and normal pregnancy.Methods Immunohistochemistry(S-P technique) was used to detect the expression of MMP-9 and TIMP-1 in endometrium of selected cases consisting of 30 unexplained infertility and 20 normal endometrium.Results The expression of MMP-9 and TIMP-1 in normal endometrium could be observed in glandular epithelium and stromal cells during different phase.They expressed low in proliferative phase,but obviously higher in secretory phase,which showed significant difference in statistics(P0.05).But in unexplained infertility their weak expression was noted during proliferative phase and secretory phase.Between the expression levels of infertility and normal endometrium,the difference was significant(P0.05).Conclusion The weak expression of MMP-9 and TIMP-1 will reduce the potential of endometrial acceptation and embryo implantation,and accordingly may bring about infertility.Keywords:
Unexplained infertility
Matrix metalloproteinase 9
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Objective To study the expression of leukemia inhibitory factor(LIF) in cycling endometrium with primary unexplained infertility,normal endometrium and normal early pregnant deciduas,to explore the relationship between the expression of LIF in primary unexplained infertility and normal pregnancy.Methods Immunohistochemistry(S-P technique) and pathologic image semi-quantification were used to detect the expression of LIF in endometrium of selected cases,which are 30 samples of primary unexplained infertility,20 normal early pregnant deciduas and 15 normal endometrium.Results The cells positive for these soluble proteinases were found in the epithelial in all endometrial samples.Semi-quantitative analysis showed that LIF was weaker in the endometrial glandular cells of primary unexplained infertility women than in that the control group.Conclusion In primary unexplained infertility women,the low expression of LIF in the implantation window phase may cause the failure of implantation and bring about infertility.
Unexplained infertility
Primary infertility
Female infertility
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To study the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-3 (TIMP-3) protein in the implantation window phase of endometrium and the role of MMP-9 and TIMP-3 on embryo implantation.Immunohistochemical analysis was employed to demonstrate the population of the MMP-9 and TIMP-3 positive cell in endometrium of different phases of menstrual cycle.The positive cells of these soluble proteinases were found to be located in the endometrial epithelial cells and stromal cells. The quantitative analysis of MMP-9 and TIMP-3 proteins demonstrated an increase in staining exent from proliferative endometrium to the endometrium of implatation window phase, and an decrease to late-secretory endometrium in comparison with the implantation window phase.Expression of MMP-9 and TIMP-3 in the implantation window phases of endometrium is specific and may play an important role in regulating the depth of trophoblast invasion during embryo implantation and may be involved in endometrial stromal breakdown during menstruation.
Trophoblast
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Objective : To observe the expression of matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of matrix metalloproteinase-1(TIMP-1) in endometriosis(EMs),and to study the possible roles of MMP-3 and TIMP-1 in the pathogenesis of EMs.Method: Immunohistochemical method was employed to detect the expression of MMP3 and TIMP-1 in ectopic endometrium(40 cases) and ectopic endometrium(42 cases) from women with EMs and normal endometrium(38 cases).Result: The levels of MMP-3 in ectopic endometrium tissues of EMs were significantly higher than those in the ectopic and normal endometrium(P 0.01).The expression of TIMP-1 in ectopic and eutopic endometrium of EMs was lower than that in the normal endometrium.There was significant difference in the positive expression ratio between them(P 0.01).Conclusion: The high expression of MMP-3 in EMs and lower expression of TIMP-1 in EMs resulting the higher ratio of MMP-3/TIMP-1 can contribute to the ectopic endometrium having stronger invasive ability than the normal endometrium.
MMP3
Matrix metalloproteinase 9
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Objective To explore the relationship between the expression of CD44 in endometrium and infertility,so that the mechanism of infertility was elucidated. Methods The level of expression of CD44 in 41 unknown reason infertility and 35 normal endometrium was measured by immuno-histochemical method(S-P technique).Results In glandular epithelium and stromal cells of normal endometrium,the weak expression of CD44 was observed during proliferative phase,the expression was increased gradually in secretory phase,and the highest expression in mid-secretory phase,decreased in late secretory phase.In infertility,there was weak expression in proliferative phase,the expression increased gradually in secretory phase(P0.05),there was not significant difference between the expression of mid-secretory and early or late secretory phase(P0.05).Conclusion The anormal expression of CD44 in infertility will reduce endometrium’s acceptation,which led to the failure of imbed.
Unexplained infertility
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Decidua
Decidualization
Unexplained infertility
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Objective To detect the expression of matrixmetalloproteinase-9(MMP-9) and tissue inhibitor of metalloproteinase-1 protein(TIMP-1) in cycling endometrium of patients with unexplained infertility,normal endometrium and normal early pregnant deciduas and explore the relationship between the expression of MMP-9 and TIMP-1 in unexplained infertility and normal pregancy.Methods Immunohistochememstry(S-P technique) and pathologic image semi-quantification were used to detect the expression of MMP-9 and TIMP-1 in endometrium of 30 unexplained infertility patients and 20 normal early pregnant deciduas and 20 normal endometrium.Results The expression of MMP-9 and TIMP-1 in normal early pregnant deciduas was the highest,showing significant difference as compared with other two groups(P0.05) The expression of MMP-9 and TIMP-1 was also high in normal endometrium as compared with other two groups(P0.05).But the expression of MMP-9 and TIMP-1 in endometrium of patients with unexplained infertility was significantly reduced as compared with other two groups(P0.05).Conclusion In unexplained infertility women,the low expression of MMP-9 and TIM P-1 protein in the implantation window phase may cause the failure of implantation and results in the infertility.
Unexplained infertility
Matrix metalloproteinase 9
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During the secretory phase of the menstrual cycle, the composition of extracellular matrix (ECM) in endometrium changes to favour implantation. In the present study, we have analysed whether some cases of unexplained infertility and recurrent abortions could be explained by abnormal production or turnover of endometrial ECM. Comparison of mRNA levels of a panel of collagens, matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinases (TIMP) and cathepsins in the samples revealed higher levels of type I collagen, MMP-2 and cathepsin H and decreased levels of TIMP-3 mRNA in mid-secretory endometrium of patients with unexplained infertility and/or recurrent miscarriages when compared with normal mid-secretory endometrium. Furthermore, changes were also seen in the levels of type I collagen and TIMP-3 mRNA between the proliferative and mid-secretory phases of normal endometrium. The results suggest an altered ECM turnover in the endometrium of patients with fertility disorders prior to implantation.
Unexplained infertility
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Endometrium undergoes regular, cyclic tissue remodeling mostly associated to the endocrine system status. It is well-known fact that steroid hormones are strongly responsible for changes in endometrium. The precise mechanism of their action is still under investigation. The aim of the study was to evaluate the expression of metalloproteinases 2 and 7 (MMP-2, -7) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in human endometrium in relation to serum concentrations of estradiol and progesterone during different phases of menstrual cycle.The study material consisted of 52 biopsy samples; 12 obtained in the proliferative phase, 11 in the secretory phase and 29 during menstruation. Expression of MMP-2, MMP-7 and TIMP-1 was assessed by immunohistochemistry. Serum concentrations of estradiol and progesterone at time of biopsy were evaluated by immunochemistry assay. Results of the study were statistically assessed by linear regression model.Increased serum concentration of estradiol was associated with increased MMP-2 expression in proliferative phase but decreased in secretory phase and during menstruation. No significant relationship was found between progesterone concentration and MMP-2 expression. Moreover, no difference in the expression of MMP-7 and TIMP-1 in the endometrium in relation to hormone levels and menstrual cycle phases were observed.The results of the study indicate that estradiol influence MMP-2 expression in the endometrium depends on the phase of menstrual cycle. Such relationships were not found for MMP-7 and TIMP-1 and further tests clarifying association between estradiol and MMPs are needed.
Progesterone receptor
Menstruation
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To investigate the expressions of matrix metalloproteinase -2, -3 (MMP-2,-3) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in internal uterine endometriosis tissue and endometrium from women with and without endometriosis throughout the menstrual cycle.Immunohistochemical staining of tissues was performed to study the expressions and locations of MMP-2, MMP-3, TIMP-2 between women with and without endometriosis. The real-time PCR technique was applied to detected the mRNA expressions of MMP-2, MMP-3 and TIMP-2.We found that ectopic endometrium from patients with endometriosis expressed higher levels of MMP-2 and MMP-3 and lower levers of TIMP-2 than normal controls did (P < 0.05). MMP-2 and MMP-3 were detected strongly in both stromal and epithelial cells of ectopic endometrium from patients with endometriosis, when mostly detected in the epithelial cells in the control group. All eutopic and ectopic endometrium samples from women with and without endometriosis throughout the menstrual cycle showed similar expressions of MMP-2, MMP-3 and TIMP-2. Quantitative expressions of MMP-2 mRNA, MMP-3 mRNA and TIMP-2 mRNA were significantly lower in eutopic endometrium from controls compared with ectopic endometrium from patients with endometriosis (P < 0.05). Eutopic endometrium from controls in the proliferative phase showed significantly increased expressions of MMP-2 mRNA compared with that in the secretory phase (P < 0.05).The results suggest that ectopic endometrium with adenomyosis has more invasiveness and is prone to peritoneal implantation maybe to involved in the high expressions of MMP-2 and MMP-3 and the less expressions of TIMP-2 than endometrium from women without adenomyosis does.
Adenomyosis
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Immunostaining
Unexplained infertility
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