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Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators.

Publication ,  Journal Article
Chi, R-PA; Wang, T; Adams, N; Wu, S-P; Young, SL; Spencer, TE; DeMayo, F
Published in: J Clin Endocrinol Metab
April 1, 2020

CONTEXT: Poor uterine receptivity is one major factor leading to pregnancy loss and infertility. Understanding the molecular events governing successful implantation is hence critical in combating infertility. OBJECTIVE: To define Progesterone Receptor (PGR)-regulated molecular mechanisms and epithelial roles in receptivity. DESIGN: RNA-sequencing and PGR-ChIP-seq were conducted in parallel to identify PGR-regulated pathways during the Window of implantation (WOI) in endometrium of fertile women. SETTING: Endometrial biopsies from the proliferative and mid-secretory phases were analyzed. PATIENTS OR OTHER PARTICIPANTS: Participants were fertile, reproductive aged (18-37 years) women with normal cycle length, and without any history of dysmenorrhea, infertility, or irregular cycles. In total, 42 endometrial biopsies obtained from 42 women were analyzed in this study. INTERVENTIONS: There were no interventions during this study. MAIN OUTCOME MEASURES: Here we measured the alterations in gene expression and PGR occupancy in the genome during the WOI, based on the hypothesis that PGR binds uterine chromatin cycle dependently to regulate genes involved in uterine cell differentiation and function. RESULTS: 653 genes were identified with regulated PGR binding and differential expression during the WOI. These were involved in regulating inflammatory response, xenobiotic metabolism, epithelial mesenchymal transition, cell death, interleukin/Signal Transducer And Activator Of Transcription (STAT) signaling, estrogen response, and Mammalian target of rapamycin complex 1 (MTORC1) response. Transcriptome of the epithelium identified 3052 differentially expressed genes, of which 658 were uniquely regulated. Transcription factors Interferon Regulatory Factor 8 (IRF8) and Myocyte Enhancer Factor 2C (MEF2C) were found to be regulated in the epithelium during the WOI at the protein level, suggesting potentially important functions that are previously unrecognized. CONCLUSION: PGR binds the genomic regions of genes regulating critical processes in uterine receptivity and function.

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Published In

J Clin Endocrinol Metab

DOI

EISSN

1945-7197

Publication Date

April 1, 2020

Volume

105

Issue

4

Start / End Page

e1419 / e1439

Location

United States

Related Subject Headings

  • Young Adult
  • Transcriptome
  • Receptors, Progesterone
  • Humans
  • Fertility
  • Female
  • Epithelial Cells
  • Endometrium
  • Endocrinology & Metabolism
  • Embryo Implantation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chi, R.-P., Wang, T., Adams, N., Wu, S.-P., Young, S. L., Spencer, T. E., & DeMayo, F. (2020). Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators. J Clin Endocrinol Metab, 105(4), e1419–e1439. https://doi.org/10.1210/clinem/dgz117
Chi, Ru-Pin Alicia, Tianyuan Wang, Nyssa Adams, San-Pin Wu, Steven L. Young, Thomas E. Spencer, and Francesco DeMayo. “Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators.J Clin Endocrinol Metab 105, no. 4 (April 1, 2020): e1419–39. https://doi.org/10.1210/clinem/dgz117.
Chi R-PA, Wang T, Adams N, Wu S-P, Young SL, Spencer TE, et al. Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators. J Clin Endocrinol Metab. 2020 Apr 1;105(4):e1419–39.
Chi, Ru-Pin Alicia, et al. “Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators.J Clin Endocrinol Metab, vol. 105, no. 4, Apr. 2020, pp. e1419–39. Pubmed, doi:10.1210/clinem/dgz117.
Chi R-PA, Wang T, Adams N, Wu S-P, Young SL, Spencer TE, DeMayo F. Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators. J Clin Endocrinol Metab. 2020 Apr 1;105(4):e1419–e1439.
Journal cover image

Published In

J Clin Endocrinol Metab

DOI

EISSN

1945-7197

Publication Date

April 1, 2020

Volume

105

Issue

4

Start / End Page

e1419 / e1439

Location

United States

Related Subject Headings

  • Young Adult
  • Transcriptome
  • Receptors, Progesterone
  • Humans
  • Fertility
  • Female
  • Epithelial Cells
  • Endometrium
  • Endocrinology & Metabolism
  • Embryo Implantation