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Updated: Feb 3, 2026

Isolation of Human Endometrial Stromal Cells for In Vitro Decidualization
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Negative elongation factor is essential for endometrial function.

Sylvia C Hewitt1, Rong Li2, Nyssa Adams2

  • 1Receptor Biology Section, Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|October 18, 2018
PubMed
Summary

The negative elongation factor (NELF) complex is crucial for coordinating uterine responses during pregnancy. Disruption of NELF-mediated pausing impairs endometrial decidual development and leads to infertility in mice.

Keywords:
NELFPol II pausingdecidualizationuterus

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Area of Science:

  • Reproductive Biology
  • Molecular Biology
  • Genetics

Background:

  • RNA polymerase II (Pol II) pausing, regulated by the negative elongation factor (NELF) complex, controls gene expression dynamics.
  • Pol II pausing at uterine genes suggests a role in reproductive processes and pregnancy maintenance.
  • Endometrial decidualization is vital for successful pregnancy establishment and requires precise hormonal signaling.

Purpose of the Study:

  • To investigate the role of NELF-mediated transcriptional pausing in endometrial function and decidualization.
  • To determine if NELF-B subunit deletion impacts uterine response to decidual stimuli.
  • To assess the necessity of NELF-B and NELF-E in human endometrial stromal cell decidualization.

Main Methods:

  • Generation of uterus-specific NELF-B knockout (NELF-B UtcKO) mice using PgrCre.
  • Assessment of uterine decidual response in NELF-B UtcKO mice.
  • In vitro studies using small interfering RNA (siRNA) to suppress NELF-B and NELF-E in human endometrial stromal cells.
  • Analysis of extracellular matrix components, prolactin, and prostaglandin synthesis-related gene expression.

Main Results:

  • NELF-B UtcKO female mice exhibited infertility.
  • While initial decidual response was comparable to controls, NELF-B UtcKO mice failed to achieve a full decidual response.
  • NELF-B-deficient stromal cells showed altered extracellular matrix, elevated Prl8a2, and modified prostaglandin-related gene expression.
  • Suppression of NELF-B or NELF-E in human endometrial stromal cells inhibited decidualization, evidenced by impaired PRL and IGFBP1 induction.

Conclusions:

  • NELF-mediated transcriptional pausing is essential for coordinating endometrial responses critical for pregnancy.
  • Disruption of NELF function leads to impaired uterine decidual development and infertility.
  • These findings highlight NELF as a key regulator of endometrial receptivity and pregnancy success.