ABSTRACT
The aim of this study was to investigate the expression of macrophage migration inhibitory factor (MMIF),hypoxia-inducible factor-1 α (HIF-1 αt) and vascular endothelial growth factor (VEGF) in the serum and endometrial tissues of patients with endometriosis (EM) and the clinical significance.Eighty EM patients [American Reproductive Association stage I (n=20),stage Ⅱ (n=22),stage Ⅲ (n=21) and stage Ⅳ (n=17)] were enrolled and divided into mild (10-14 points,n=28),moderate (16-24 points,n=27) and severe (26-30 points,n=25) dysmenorrhea groups.The control group included 40 healthy women of childbearing age who underwent routine healthcare examinations in the enrolment period.The expression of MMIF,HIF-1α and VEGF in the serum and endometrial tissues was measured by enzyme-linked immunosorbent assay and Western blotting,respectively.Meanwhile,the sensitivity and specificity of serum MMIF,HIF-1α,and VEGF when separately used as single indexes or jointly used as one index were examined as well.The results showed that serum concentrations of MMIF,HIF-1α,and VEGF were significantly higher in EM patients than in controls (P＜0.05).The expression of all three proteins in both serum and endometrial tissues increased significantly with the R-AFS stage (P＜0.05) and with dysmenorrheal severity (P＜0.05).The sensitivity and specificity of the combined detection of serum MMIF,HIF-1α,and VEGF levels were significantly higher than those of single index detection (P＜0.05).In conclusion,the expression of MMIF,HIF-1α,and VEGF in the serum and endometrial tissues may be used to assess the stage of EM and the severity of dysmenorrhea.Combined evaluation of MMIF,HIF-1α,and VEGF significantly improves the diagnostic sensitivity and specificity.
ABSTRACT
The aim of this study was to investigate the expression of macrophage migration inhibitory factor (MMIF),hypoxia-inducible factor-1 α (HIF-1 αt) and vascular endothelial growth factor (VEGF) in the serum and endometrial tissues of patients with endometriosis (EM) and the clinical significance.Eighty EM patients [American Reproductive Association stage I (n=20),stage Ⅱ (n=22),stage Ⅲ (n=21) and stage Ⅳ (n=17)] were enrolled and divided into mild (10-14 points,n=28),moderate (16-24 points,n=27) and severe (26-30 points,n=25) dysmenorrhea groups.The control group included 40 healthy women of childbearing age who underwent routine healthcare examinations in the enrolment period.The expression of MMIF,HIF-1α and VEGF in the serum and endometrial tissues was measured by enzyme-linked immunosorbent assay and Western blotting,respectively.Meanwhile,the sensitivity and specificity of serum MMIF,HIF-1α,and VEGF when separately used as single indexes or jointly used as one index were examined as well.The results showed that serum concentrations of MMIF,HIF-1α,and VEGF were significantly higher in EM patients than in controls (P＜0.05).The expression of all three proteins in both serum and endometrial tissues increased significantly with the R-AFS stage (P＜0.05) and with dysmenorrheal severity (P＜0.05).The sensitivity and specificity of the combined detection of serum MMIF,HIF-1α,and VEGF levels were significantly higher than those of single index detection (P＜0.05).In conclusion,the expression of MMIF,HIF-1α,and VEGF in the serum and endometrial tissues may be used to assess the stage of EM and the severity of dysmenorrhea.Combined evaluation of MMIF,HIF-1α,and VEGF significantly improves the diagnostic sensitivity and specificity.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the roles of matrix metalloproteinase-1(MMP-1) and tissue inhibitor of metalloproteinase-1(TIMP-1) in the pathogenesis of endometriosis and the effects of estrogen and progestin on their expression.</p><p><b>METHODS</b>Immunohistochemistry and RT-PCR were employed to detect the expression of MMP-1 and TIMP-1 in the ectopic tissues of 35 patients with endometriosis, 22 eutopic endometrium tissues from women with endometriosis and 28 normal controls. Fifty-nine nude mice were injected with human late secretory endometrial chippings and randomized into estrogen group, progestin group, estrogen-progestin group and control group with corresponding treatments. The implantation rates and graft morphology were observed and MMP-1 and TIMP-1 expressions in the grafts detected by immunohistochemistry.</p><p><b>RESULTS</b>Typical endometrial glands and stroma were observed in all the groups with comparable implantation rates. The administration of progestin was associated with multiple peritoneal implantation sites and significantly larger implants. The transplanted endometria showed proliferative or secretory changes with estrogen or progestin administration. MMP-1 expression significantly increased and TIMP-1 expression decreased with increased MMP-1/TIMP-1 ratio in human and nude mouse ectopic endometria in comparison with those in normal endometria (P<0.05, P<0.01). MMP-1 expression was higher in estrogen and estrogen-progestin groups than in the control group, and was lower in the 3 sexual hormone-treated groups than in the control group. MMP-1 mRNA expression in the eutopic endometrium was significantly higher than that in the normal endometria.</p><p><b>CONCLUSION</b>Progestrin can not inhibit MMP-1 expression or the effect of estrogen on ectopic endometrium known as progestin resistance. The high expression of MMP-1 and low expression of TIMP-1 in endometriotic tissues confer strong invasiveness of ectopic endometrial tissue, especially in eutopic endometrial tissue, and may play an important role in the pathogenesis of endometriosis.</p>