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      Expression and shedding of CD44 in the endometrium of women with endometriosis and modulating effects of vitamin D: A randomized exploratory trial.

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          Abstract

          Endometriosis is an estrogen-dependent disease. The impaired estrogen and progesterone signaling over-activates the Wnt/β-catenin pathway in endometriosis patients, which can explain the increased invasion potency of endometrial cells derived from the endometrium of women with endometriosis. The regulatory effects of vitamin D on Wnt/β-catenin pathway were demonstrated by previous studies. According to gene prioritization method, among Wnt target genes, CD44 was in high ranking in relation to endometriosis. The aim of this study is to investigate the expression of CD44 in the endometrium of women with endometriosis and to study the effects of vitamin D on its expression. This prospective study was performed, during a 12 months period from December 2015 to November 2016, on healthy women as the control group (n = 14) and endometriosis patients (n = 34). The endometriosis patients randomly divided into two groups: One group treated according to the routine protocol and the other group, alongside the routine protocol, took 50,000 IU vitamin D weekly for 12-14 weeks. Blood, endometrial fluid, and endometrial tissue samples were obtained from the control group and endometriosis groups before and after the intervention. We used in silico gene prioritization to study the relevance of CD44. The expression of CD44 was evaluated using the techniques of Western blot, real-time polymerase chain reaction, and ELISA. The eutopic endometrium of women with endometriosis in mid-secretory phase expressed significantly higher levels of CD44s, CD44V, and CD44v6. The concentration of soluble CD44 in the serum and endometrial fluid of endometriosis patients was higher than of healthy women. The expression level of CD44s, CD44V, and CD44v6 in the eutopic endometrium as well as the concentration of soluble CD44 in the endometrial fluid was decreased after modification of the circulating levels of 25(OH)D. It seems that the increased expression and extensive shedding of CD44 in eutopic endometrium play a role in the pathogenesis of endometriosis. Vitamin D can control and modify this process at least in part. We suggest more in vivo investigations on the therapeutic potency of vitamin D in endometriosis.

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          Author and article information

          Journal
          J. Steroid Biochem. Mol. Biol.
          The Journal of steroid biochemistry and molecular biology
          Elsevier BV
          1879-1220
          0960-0760
          April 2018
          : 178
          Affiliations
          [1 ] Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
          [2 ] Department of Obstetrics and Gynecology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
          [3 ] Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
          [4 ] Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
          [5 ] Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: sobhania@sina.tums.ac.ir.
          Article
          S0960-0760(17)30365-5
          10.1016/j.jsbmb.2017.12.001
          29229305
          6c038b24-9e7e-425e-953b-73a66efb636e

          CD44, Endometriosis, Endometrium, Vitamin D

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