For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
12
views
32
references
 Top references
cited by
12
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      81
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Activating transcription factor 3 promotes embryo attachment via up-regulation of leukemia inhibitory factor in vitro

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          A receptive endometrium is essential for maternal-embryonic molecular communication during implantation. However, the specific molecular regulatory mechanisms of the endometrial capacity remain poorly understood. Here, we examined activating transcription factor 3 (ATF3) expression in human endometria and the functional effect of ATF3 on embryo attachment in vitro.

          Methods

          Immunohistochemistry (IHC) was used to assess the ATF3 expression patterns in human endometria. Quantitative real-time PCR (qRT-PCR), western blotting and immunofluorescence (IF) studies were applied to explore ATF3 expression in Ishikawa cells upon estrogen (E 2) and medroxyprogesterone acetate (MPA) treatment. qRT-PCR and western blotting were performed to inspect LIF (leukemia inhibitory factor) expression after enhancement or inhibition of ATF3, and a luciferase reporter assay and ChIP-PCR were used to confirm the regulatory mechanism of ATF3 to LIF. Endometrial epithelial capacity was assessed by an in vitro model of attachment of BeWo spheroids to Ishikawa cells. Western blotting was performed to compare the expression of ATF3 in endometrial samples of recurrent implantation failure (RIF) patients with that in samples from fertile women (FER) who had undergone no less than one successful embryo transplantation.

          Results

          ATF3 was located in human endometrial epithelial cells and stromal cells and was significantly induced by E 2 and MPA in Ishikawa cells. Adenovirus-mediated overexpression of ATF3 in Ishikawa cells activated LIF promoter activity and enhanced its expression. Accordingly, the stimulation of BeWo spheroid adhesion promoted by ATF3 was inhibited by pretreatment with a specific antibody against LIF via the antibody-blocking assay. Moreover, ATF3 was aberrantly decreased in the endometria of RIF patients.

          Conclusions

          Our findings suggest that ATF3 plays a significant role in regulating human endometrial receptivity and embryo attachment in vitro via up-regulation of leukemia inhibitory factor.

          Trial registration

          Construction and management of the Nanjing multi-center biobank. No. 2013-081-01. Registered 10 Dec. 2013.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12958-017-0260-7) contains supplementary material, which is available to authorized users.

          Related collections

          Most cited references32

          • Record: found
          • Abstract: found
          • Article: not found

          ATF3 transcription factor and its emerging roles in immunity and cancer.

          Andrew Thompson, Bryan Williams, Dakang Xu (2009)
          Activating transcription factor 3 (ATF3) is a member of the ATF/cyclic AMP response element-binding (ATF/CREB) family of transcription factors. It is an adaptive-response gene that participates in cellular processes to adapt to extra- and/or intracellular changes, where it transduces signals from various receptors to activate or repress gene expression. Advances made in understanding the immunobiology of Toll-like receptors have recently generated new momentum for the study of ATF3 in immunity. Moreover, the role of ATF3 in the regulation of the cell cycle and apoptosis has important implications for understanding susceptibility to and progression of several cancers.
          Article 0 comments Cited 120 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Natural Selection of Human Embryos: Impaired Decidualization of Endometrium Disables Embryo-Maternal Interactions and Causes Recurrent Pregnancy Loss

            Madhuri Salker, Gijs Teklenburg, Mariam Molokhia … (2010)
            Background Recurrent pregnancy loss (RPL), defined as 3 or more consecutive miscarriages, is widely attributed either to repeated chromosomal instability in the conceptus or to uterine factors that are poorly defined. We tested the hypothesis that abnormal cyclic differentiation of endometrial stromal cells (ESCs) into specialized decidual cells predisposes to RPL, based on the observation that this process may not only be indispensable for placenta formation in pregnancy but also for embryo recognition and selection at time of implantation. Methodology/Principal Findings Analysis of mid-secretory endometrial biopsies demonstrated that RPL is associated with decreased expression of the decidual marker prolactin (PRL) but increased levels of prokineticin-1 (PROK1), a cytokine that promotes implantation. These in vivo findings were entirely recapitulated when ESCs were purified from patients with and without a history of RPL and decidualized in culture. In addition to attenuated PRL production and prolonged and enhanced PROK1 expression, RPL was further associated with a complete dysregulation of both markers upon treatment of ESC cultures with human chorionic gonadotropin, a glycoprotein hormone abundantly expressed by the implanting embryo. We postulated that impaired embryo recognition and selection would clinically be associated with increased fecundity, defined by short time-to-pregnancy (TTP) intervals. Woman-based analysis of the mean and mode TTP in a cohort of 560 RPL patients showed that 40% can be considered “superfertile”, defined by a mean TTP of 3 months or less. Conclusions Impaired cyclic decidualization of the endometrium facilitates implantation yet predisposes to subsequent pregnancy failure by disabling natural embryo selection and by disrupting the maternal responses to embryonic signals. These findings suggest a novel pathological pathway that unifies maternal and embryonic causes of RPL.
            Article 0 comments Cited 107 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The role of the endometrium and embryo in human implantation.

              Jolene Diedrich, B Fauser, P. Devroey … (2015)
              Despite many advances in assisted reproductive technologies (ART), implantation rates are still low. The process of implantation requires a reciprocal interaction between blastocyst and endometrium, culminating in a small window of opportunity during which implantation can occur. This interaction involves the embryo, with its inherent molecular programme of cell growth and differentiation, and the temporal differentiation of endometrial cells to attain uterine receptivity. Implantation itself is governed by an array of endocrine, paracrine and autocrine modulators, of embryonic and maternal origin. Implantation failure is thought to occur as a consequence of impairment of embryo developmental potential and/or impairment of uterine receptivity and the embryo-uterine dialogue. Therefore a better comprehension of implantation, and the relative importance of the factors involved, is warranted. New techniques for monitoring changes in the endometrium and/or the embryo at the level of gene regulation and protein expression may lead to the identification of better markers for implantation. Moreover, the use of predictive sets of markers may prove to be more reliable than a single marker. Continuing refinements to ART protocols, such as optimizing ovarian stimulation regimens, the timing of human chorionic gonadotrophin injection, or the timing of embryo transfer, should help to increase implantation rates further.
              Article 0 comments Cited 76 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Xi Cheng: 15751866735@163.com
                Jingyu Liu: lianjing1216@Hotmail.com
                Huizhi Shan: Sophialshan@163.com
                Lihua Sun: lihua-sun@163.com
                Chenyang Huang: dianshui19901562@qq.com
                Qiang Yan: 602172356@qq.com
                Ruiwei Jiang: jrw0823@163.com
                Lijun Ding: xmljding@163.com
                Yue Jiang: jiangyue85@163.com
                Jianjun Zhou: zhou6jj@hotmail.com
                Guijun Yan: yanguijun55@163.com
                Haixiang Sun: stevensunz@163.com
                Journal
                Journal ID (nlm-ta): Reprod Biol Endocrinol
                Journal ID (iso-abbrev): Reprod. Biol. Endocrinol
                Title: Reproductive Biology and Endocrinology : RB&E
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1477-7827
                Publication date (Electronic): 2 June 2017
                Publication date PMC-release: 2 June 2017
                Publication date Collection: 2017
                Volume: 15
                Electronic Location Identifier: 42
                Affiliations
                [1 ]ISNI 0000 0004 1800 1685, GRID grid.428392.6, Reproductive Medicine Center, , The Affiliated Drum Tower Hospital of Nanjing University Medical School, ; Nanjing, 210008 People’s Republic of China
                [2 ]GRID grid.412523.3, Reproductive Medicine Center, , Shanghai Ninth People’s Hospital Affiliated Shanghai JiaTong University School of Medicine, ; Shanghai, 200011 People’s Republic of China
                [3 ]Collaborative Innovation Platform for Reproductive Biology and Technology of Nanjing University Medical School, Nanjing, 210008 People’s Republic of China
                [4 ]Center of Reproductive Medicine, Nanjing Jinling Hospital, the Medical School of Nanjing University, Nanjing, 210002 China
                Article
                Publisher ID: 260
                DOI: 10.1186/s12958-017-0260-7
                PMC ID: 5457579
                PubMed ID: 28577574
                SO-VID: 41d519e4-18fd-44d6-9c3e-91e3cc2abe0f
                Copyright © © The Author(s). 2017
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 4 September 2016
                Date accepted : 23 May 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 31571189
                Award ID: 81571402
                Award Recipient :
                Funded by: a special grant for clinical medicine science of Jiangsu Province
                Award ID: BL2014003
                Award Recipient :
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2017

                ScienceOpen disciplines: Human biology
                Keywords: atf3,lif,embryo adhesion,recurrent implantation failure
                Data availability:
                ScienceOpen disciplines: Human biology
                Keywords: atf3, lif, embryo adhesion, recurrent implantation failure

                Comments

                Comment on this article

                scite_

                Similar content81

                See all similar

                Cited by12

                See all cited by

                Most referenced authors334

                See all reference authors