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Decidualization of Human Endometrial Stromal Fibroblasts is a Multiphasic Process Involving Distinct Transcriptional Programs

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Abstract

Decidual stromal cells differentiate from endometrial stromal fibroblasts (ESFs) under the influence of progesterone and cyclic adenosine monophosphate (cAMP) and are essential for implantation and the maintenance of pregnancy. They evolved in the stem lineage of placental (eutherian) mammals coincidental with the evolution of implantation. Here we use the well-established in vitro decidualization protocol to compare early (3 days) and late (8 days) gene transcription patterns in immortalized human ESF. We document extensive, dynamic changes in the early and late decidual cell transcriptomes. The data suggest the existence of an early signal transducer and activator of transcription (STAT) pathway dominated state and a later nuclear factor κB (NFKB) pathway regulated state. Transcription factor expression in both phases is characterized by putative or known progesterone receptor (PGR) target genes, suggesting that both phases are under progesterone control. Decidualization leads to proliferative quiescence, which is reversible by progesterone withdrawal after 3 days but to a lesser extent after 8 days of decidualization. In contrast, progesterone withdrawal induces cell death at comparable levels after short or long exposure to progestins and cAMP. We conclude that decidualization is characterized by a biphasic gene expression dynamic that likely corresponds to different phases in the establishment of the fetal—maternal interface.

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Authors and Affiliations

  1. Yale Systems Biology Institute, 850 West Campus Drive, West Haven, CT, 06516, USA

    Kalle T. Rytkönen PhD, Eric M. Erkenbrack PhD & Günter P. Wagner PhD

  2. Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT, USA

    Kalle T. Rytkönen PhD, Eric M. Erkenbrack PhD & Günter P. Wagner PhD

  3. Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Kiinamyllynkatu, Finland

    Kalle T. Rytkönen PhD & Matti Poutanen PhD

  4. Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland

    Kalle T. Rytkönen PhD & Laura L. Elo PhD

  5. Cincinnati Children’s Hospital and Medical Center, Cincinnati, OH, USA

    Mihaela Pavlicev PhD

  6. Department of Obstetrics, Yale Medical School, New Haven, CT, USA

    Günter P. Wagner PhD

  7. Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA

    Günter P. Wagner PhD

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  1. Kalle T. Rytkönen PhD
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Data described in this manuscript were acquired at Yale University.

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Rytkönen, K.T., Erkenbrack, E.M., Poutanen, M. et al. Decidualization of Human Endometrial Stromal Fibroblasts is a Multiphasic Process Involving Distinct Transcriptional Programs. Reprod. Sci. 26, 323–336 (2019). https://doi.org/10.1177/1933719118802056

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