Molecular Signaling in Decidualization

Summary

Principal Investigator: SANJOY KUMAR DAS
Abstract: Uterine stromal cell decidualization is integral to successful embryo implantation which is gateway to pregnancy establishment. This process is characterized by stromal cell proliferation and differentiation into decidual cells with polyploidy. Although various signaling molecules including cyclin D3 (a cell cycle regulator), HB-EGF (a heparinbinding EGF-like growth factor) and Hoxa-10 (a homeotic protein) are implicated in decidualization, the precise mechanisms by which these factors regulate this process and whether they are critical to decidualization are not known, except the essential role of Hoxa-10 in this process. We hypothesize that the success of decidualization is dependent on a balance between positive and negative regulators, directing proliferation and differentiation essential to this process;a tipping of this balance will lead to defective decidualization. We propose that Hoxa-10 and HB-EGF signaling converge to a common downstream cell cycle regulatory circuitry consisting of a positive cell cycle regulator cyclin D3 and negative cell cycle regulator cyclin G1 to appropriately balance proliferation and differentiation for achieving full complement of decidualization.
Funding Period: ----------------2009 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. ncbi Developmental regulation of decidual cell polyploidy at the site of implantation
    Julie M Sroga
    Division of Reproductive Sciences, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
    Front Biosci (Schol Ed) 4:1475-86. 2012
  2. pmc Overexpression of cyclin D3 improves decidualization defects in Hoxa-10(-/-) mice
    Julie M Sroga
    Obstetrics and Gynecology, University of Cincinnati, Ohio 45267, USA
    Endocrinology 153:5575-86. 2012
  3. pmc Epigenetic changes through DNA methylation contribute to uterine stromal cell decidualization
    Fei Gao
    Division of Reproductive Sciences and Perinatal Institute, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
    Endocrinology 153:6078-90. 2012
  4. ncbi Regional development of uterine decidualization: molecular signaling by Hoxa-10
    Sanjoy K Das
    Reproductive Sciences, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    Mol Reprod Dev 77:387-96. 2010
  5. pmc GPR30 activation opposes estrogen-dependent uterine growth via inhibition of stromal ERK1/2 and estrogen receptor alpha (ERα) phosphorylation signals
    Fei Gao
    Division of Reproductive Sciences, The Perinatal Institute, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    Endocrinology 152:1434-47. 2011
  6. pmc Mouse primary uterine cell coculture system revisited: ovarian hormones mimic the aspects of in vivo uterine cell proliferation
    Daesuk Chung
    Division of Reproductive Sciences, The Perinatal Institute, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    Endocrinology 152:3246-58. 2011
  7. pmc Decidual cell polyploidization necessitates mitochondrial activity
    Xinghong Ma
    Division of Reproductive Sciences, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America
    PLoS ONE 6:e26774. 2011
  8. pmc Nucleolar Sik-similar protein (Sik-SP) is required for the maintenance of uterine estrogen signaling mechanism via ERα
    Daesuk Chung
    Division of Reproductive Sciences, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
    Mol Endocrinol 26:385-98. 2012

Scientific Experts

  • SANJOY KUMAR DAS
  • Fei Gao
  • Xinghong Ma
  • Julie M Sroga
  • Daesuk Chung
  • Alicia B Ostmann
  • Allison Rusie
  • Jennifer Hemingway
  • Xiaonan Hou
  • Alicia Ostmann
  • Anil G Jegga

Detail Information

Publications8

  1. ncbi Developmental regulation of decidual cell polyploidy at the site of implantation
    Julie M Sroga
    Division of Reproductive Sciences, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
    Front Biosci (Schol Ed) 4:1475-86. 2012
    ..Here we review the mechanisms involved in polyploidy cell formation in normal developmental processes, with focus on known regulatory aspects in decidual cells...
  2. pmc Overexpression of cyclin D3 improves decidualization defects in Hoxa-10(-/-) mice
    Julie M Sroga
    Obstetrics and Gynecology, University of Cincinnati, Ohio 45267, USA
    Endocrinology 153:5575-86. 2012
    ..Collectively, these results demonstrate that cyclin D3 expression influences a host of genes involved in decidualization and can improve decidualization in Hoxa-10(-/-) mice...
  3. pmc Epigenetic changes through DNA methylation contribute to uterine stromal cell decidualization
    Fei Gao
    Division of Reproductive Sciences and Perinatal Institute, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
    Endocrinology 153:6078-90. 2012
    ..Overall, these results suggest that uterine DNM plays a major role for successful decidualization and embryo development during early pregnancy...
  4. ncbi Regional development of uterine decidualization: molecular signaling by Hoxa-10
    Sanjoy K Das
    Reproductive Sciences, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    Mol Reprod Dev 77:387-96. 2010
    ..In this regard, this article provides an overview of potential signaling mechanisms mediated by Hoxa-10 that can influence a host of genes and cell functions necessary for propagating regional decidual development...
  5. pmc GPR30 activation opposes estrogen-dependent uterine growth via inhibition of stromal ERK1/2 and estrogen receptor alpha (ERα) phosphorylation signals
    Fei Gao
    Division of Reproductive Sciences, The Perinatal Institute, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    Endocrinology 152:1434-47. 2011
    ..Our work has uncovered a novel GPR30-regulated inhibitory event, which may be physiologically relevant in both normal and pathological situations to negatively balance ERα-dependent uterine growth regulatory functions induced by E2...
  6. pmc Mouse primary uterine cell coculture system revisited: ovarian hormones mimic the aspects of in vivo uterine cell proliferation
    Daesuk Chung
    Division of Reproductive Sciences, The Perinatal Institute, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    Endocrinology 152:3246-58. 2011
    ....
  7. pmc Decidual cell polyploidization necessitates mitochondrial activity
    Xinghong Ma
    Division of Reproductive Sciences, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America
    PLoS ONE 6:e26774. 2011
    ..Collectively, analyses of unique polyploidy markers and molecular signaling networks may be useful to further characterize functional aspects of decidual cell polyploidy at the site of implantation...
  8. pmc Nucleolar Sik-similar protein (Sik-SP) is required for the maintenance of uterine estrogen signaling mechanism via ERα
    Daesuk Chung
    Division of Reproductive Sciences, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
    Mol Endocrinol 26:385-98. 2012
    ..In conclusion, Sik-SP, an early E2-responsive nucleolar protein, is necessary to induce E2-dependent ERα-mediated appropriate physiologic responses in the uterus...