Letrozole Promotes The Expression Of Integrin αvβ3 And HOXA10 During The Implant Window In Endometriosis

Background and Objective:Endometriosis(EMT)is a chronic,estrogen-dependent inflammatory disease in which active endometrial cells are planted outside the uterine cavity.The main pathological changes were ectopic endometrium periodic bleeding and surrounding tissue fibrosis.This disease mainly occurs in reproductive women,and its main symptoms are dysmenorrhea,chronic pelvic pain,abnormal menstruation,infertility.Although the underlying mechanisms that leading to infertility in patients with endometriosis remain unclear,plenty of factors have been reported which including reduced endometrial receptivity,ovarian dysfunction,and changes in the pelvic microenvironment.At present,more and more studies have proved that endometrial receptivity is an important factor in infertility.Integrin αvβ3 is a cell surface receptor for extracellular matrix protein,located in endometrial and glandular epithelium.The expression of integrin varies periodically,and the peak time is consistent with the window period of implantation.Previous studies have shown that the expression of integrin αvβ3,a specific key integrin that plays an important role in embryo implantation,is reduced in women with infertility and endometriosis.Studies have shown that estrogen dominance can inhibit the expression of integrin αvβ3.HOXA10(homologous box gene 10)is a transcriptional regulatory gene,expressing in endometrial epithelial cells and stromal cells,which plays a key role in embryo implantation.HOXA10 can promote the proliferation and differentiation of endometrial epithelial and trophoblast cells,and regulate the expression of integrinαvβ3.The expression of HOXA10 is significantly increased during endometrial implant window period and is reduced in the endometrium of infertile women with endometriosis.Letrozole is a nonsteroidal aromatase inhibitor that inhibits the synthesis of estrogen.Studies have shown that letrozole can increase clinical pregnancy rates,but the exact mechanism remains unclear.This study hypothesizes that letrozole can regulate the expression of integrins αVβ3 and HOXA10 during the implant window in endometriosis,thereby improving endometrial receptivity and increasing pregnancy rate.Research Methods:A rat model of endometriosis was established and treated with letrozole(2ug/kg of body weight,15 consecutive days).The endometrium of rats during the window period of implantation was taken to detect the expression of integrin αVβ3 and HOXA10.Serum estrogen levels were detected also.Results:(1)In RT-PCR,compared with the control group,the expression of HOXA10 was reduced in the endometriosis group(P<0.01),and increased in the endometriosis group after letrozole administration(P<0.05).(2)In RT-PCR,compared with the control group,the expression of integrin aVβ3 was decreased in the endometriosis group(P<0.01),and increased in the endometriosis group after letrozole(P<0.01).(3)In Western blotting analysis,compared with the control group,the expression of integrin αVβ3 was decreased in the endometriosis group(P<0.05),and increased after letrozole administration(P<0.01).(4)Estrogen levels were detected by ELISA,we found that,compared with the control group,estrogen levels were increased in the endometriosis group,but the difference was not statistically significant.Estrogen levels decreased after letrozole treatment,but the difference was not statistically significant.Conclusion:Endometrial receptivity was impaired in endometriosis,but treatment with letrozole can improve it.In endometriosis,the expressions of HOXA10 and integrinαvβ3 were decreased in the endometrium during the implantation window,and letrozole upregulates their expressions.This finding provides a new therapeutic approach for improving the pregnancy rate of patients with endometriosis.