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      Thin endometrium transcriptome analysis reveals a potential mechanism of implantation failure

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          Abstract

          Aim

          Although a thin endometrium has been well recognized as a critical factor in implantation failure, little information is available regarding the molecular mechanisms. The present study investigated these mechanisms by using genome‐wide mRNA expression analysis.

          Methods

          Thin and normal endometrial tissue was obtained from a total of six women during the mid‐luteal phase of the menstrual cycle. The transcriptomes were analyzed with a microarray. Differentially expressed genes were classified according to Gene Ontology ( GO) terms and Kyoto Encyclopedia of Genes and Genomes ( KEGG) pathways.

          Results

          The study identified 318 up‐regulated genes and 322 down‐regulated genes in the thin endometrium, compared to the control endometrium. The GO and KEGG pathway analyses indicated that the thin endometrium possessed aberrantly activated immunity and natural killer cell cytotoxicity that was accompanied by an increased number of inflammatory cytokines, such as IFNγ. Various genes that were related to metabolism and anti‐oxidative stress were down‐regulated in the thin endometrium.

          Conclusion

          Implantation failure in the thin endometrium appears to be associated with an aberrantly activated inflammatory environment and aberrantly decreased response to oxidative stress.

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          Most cited references28

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          Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon?

          Pregnant females are susceptible to intracellular pathogens and are biased towards humoral rather than cell-mediated immunity. Since TH1 cytokines compromise pregnancy and TH2 cytokines are produced at the maternal-fetal interface, we hypothesize that these TH2 cytokines inhibit TH1 responses, improving fetal survival but impairing responses against some pathogens.
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            Relationship between endometrial thickness and embryo implantation, based on 1,294 cycles of in vitro fertilization with transfer of two blastocyst-stage embryos.

            To evaluate the relationship between endometrial thickness and clinical outcome of IVF and ET. Retrospective study. Private assisted reproductive technology center. One thousand two hundred and ninety-four infertility patients. IVF and fresh autologous ET of two blastocyst-stage embryos, including at least one good-quality blastocyst. Clinical pregnancy rate (PR) and spontaneous abortion rate. Endometrial thickness was greater in cycles resulting in pregnancy than in cycles not resulting in pregnancy (11.9 vs. 11.3 mm, respectively). Clinical pregnancy rates increased gradually from 53% among patients with a lining of or =16 mm. Multiple logistic regression analysis indicated significant effects of age, embryo quality, and endometrial thickness on both clinical pregnancy rates and live-birth or ongoing pregnancy rates. There was also a marginally significant trend toward decreasing rates of spontaneous pregnancy loss with increasing endometrial thickness. Clinical pregnancy and live-birth or ongoing pregnancy rates increase significantly with increasing endometrial thickness, independent of the effects of patient age and embryo quality.
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              Pathophysiologic features of "thin" endometrium.

              To characterize pathophysiologic features of a "thin" endometrium. A prospective observational study. University Hospital and City General Hospital. Patients with normal-thickness endometrium (Normal-Em group: endometrial thickness >or=8 mm; n = 57) and thin endometrium (Thin-Em group: endometrial thickness <8 mm; n = 17). Blood flow impedance of the uterine radial artery (RA) was assessed as resistance index (RI) by transvaginal color-pulsed Doppler ultrasonography. The area of glandular epithelium, the number of blood vessels, and vascular endothelial growth factor (VEGF) expression were examined in the midluteal-phase endometrium. The RA-RI in the Thin-Em group was significantly higher than in the Normal-Em group throughout the menstrual cycle. Endometrial thickness was significantly correlated with RA-RI. Growth of glandular epithelium, the number of blood vessels, and VEGF expression were significantly lower in the Thin-Em group than in the Normal-Em group. A "thin" endometrium was characterized by high blood flow impedance of RA, poor epithelial growth, decreased VEGF expression, and poor vascular development.
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                Author and article information

                Contributors
                rmaekawa@yamaguchi-u.ac.jp
                Journal
                Reprod Med Biol
                Reprod. Med. Biol
                10.1111/(ISSN)1447-0578
                RMB2
                Reproductive Medicine and Biology
                John Wiley and Sons Inc. (Hoboken )
                1445-5781
                1447-0578
                09 April 2017
                April 2017
                : 16
                : 2 ( doiID: 10.1111/rmb2.2017.16.issue-2 )
                : 206-227
                Affiliations
                [ 1 ] Department of Obstetrics and Gynecology Yamaguchi University Graduate School of Medicine Ube Japan
                [ 2 ] Department of Obstetrics and Gynecology Saiseikai Shimonoseki General Hospital Shimonoseki Japan
                Author notes
                [*] [* ] Correspondence

                Ryo Maekawa, Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

                Email: rmaekawa@ 123456yamaguchi-u.ac.jp

                Author information
                http://orcid.org/0000-0003-0923-376X
                Article
                RMB212030
                10.1002/rmb2.12030
                5661823
                29259471
                b6774952-2f3e-4a87-a8b8-9121d9d92606
                © 2017 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 January 2017
                : 09 February 2017
                Page count
                Figures: 2, Tables: 5, Pages: 22, Words: 12689
                Funding
                Funded by: Japan Society for the Promotion of Science
                Funded by: Ministry of Education, Science, and Culture
                Award ID: 16K11091
                Award ID: 16K11142
                Award ID: 16K20191
                Award ID: 16K20192
                Award ID: 16K20194
                Award ID: 15K20145
                Award ID: 15K20146
                Award ID: 15K10719
                Award ID: 15K10720
                Award ID: 26462492
                Award ID: 26462525
                Funded by: Yamaguchi University
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                rmb212030
                April 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.2.7 mode:remove_FC converted:04.12.2017

                implantation failure,infertility,oxidative stress,thin endometrium,uterine natural killer cells

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