Zinc is essential for the transcription function of the PGC-1α/Nrf2 signaling pathway in human primary endometrial stromal cells

Am J Physiol Cell Physiol. 2020 Mar 1;318(3):C640-C648. doi: 10.1152/ajpcell.00152.2019. Epub 2020 Jan 15.

Abstract

Zinc (Zn) has antioxidant effect in different types of organs and is closely associated with human health. Endometrial receptivity is one of the most important factors in the embryo implantation and development. However, the regulatory mechanism of Zn in endometrium tissue is still unclear. In the study, we found that plasma Zn level is significantly associated with female infertility, which severely affects female reproductive health. Primary endometrial stromal cells were isolated from female endometrium and cultured in the laboratory. Zn chelator TPEN treatment reduced the expression of stem cell markers CD73, CD90, and CD105 and generated reactive oxygen species in endometrial stromal cells. However, pretreatment of Zn (zinc sulfate) is able to prevent TPEN-induced oxidative stress in vitro. By transcriptional profiling and gene ontology analysis, we found that Zn increased the cellular pluripotency signaling and extracellular matrix-receptor interaction, but reduced autophagy, endocytosis, and the nitrogen metabolism pathway. We further discovered the antioxidant function of Zn through the peroxisome proliferator-activated receptor gamma coactivator 1α/nuclear factor erythroid-2-related factor signaling pathway in endometrial stromal cells. Zn supplementation may open up an effective therapeutic approach for patients with oxidative stress-related endometrial diseases.

Keywords: antioxidant; primary endometrial stromal cells; thin endometrium; zinc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Survival / physiology
  • Cells, Cultured
  • Endometrium / diagnostic imaging
  • Endometrium / metabolism*
  • Female
  • Humans
  • NF-E2-Related Factor 2 / physiology*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / physiology*
  • Signal Transduction / physiology
  • Stromal Cells / metabolism*
  • Stromal Cells / pathology
  • Transcription, Genetic / physiology*
  • Young Adult
  • Zinc / metabolism*

Substances

  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Zinc