High estradiol concentrations induce heat shock protein 70 expression and suppress nuclear factor kappa b activation in human endometrial epithelial cells

Chin Der Chen, Shee Uan Chen, Chia Hung Chou, Mei Jou Chen, Wen Fen Wen, Szu Yuan Wu, Yu Shih Yang, Jehn Hsiahn Yang

Research output: Contribution to journalArticle

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Abstract

The high serum estradiol (E2) concentrations induced during in vitro fertilization are detrimental to endometrial receptivity and may result in lower embryo implantation rates. We have previously found that high E2 concentrations inhibit the activation of nuclear factor kappa B (NF-κB), leading to endometrial epithelial cell (EEC) apoptosis. The objective of this study is to investigate the signaling pathways through which high E2 results in NF-κB downregulation in EECs. Isolated human EECs were cultured in different concentrations of E2 (10-10, 10-9, 10-8, 10-7 M). The expression of heat shock protein 70 (Hsp70) and heat shock factor 1 (HSF-1) were upregulated under supraphysiological E2 (10-7 M) concentration, whereas phosphorylated inhibitory kappa B-alpha (pI κB-α) and NF-κB p65 subunits were downregulated. Immunohistochemistry of C57BL/ 6 mouse EECs that were exposed in vivo to high serum E2 from the administration of 20 IU of equine chorionic gonadotropin also demonstrated the same increase in HSF-1 and Hsp70 expression and a decrease in NF-κB. Immunoprecipitation of the induced Hsp70 proteins was achieved with the addition of inhibitory jB kinase gamma (IKK-γ) antibodies, and elimination of this reaction occurred after addition of hsp70 siRNA. In conclusion, high E2 concentrations enhance HSF-1 and Hsp70 expression in EECs. The induced Hsp70 forms a complex with IKK-γ and inhibits pI κB-α, which consequently suppresses NFκB activation.

Original languageEnglish
Article number87
JournalBiology of Reproduction
Volume95
Issue number4
DOIs
Publication statusPublished - Oct 1 2016

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HSP70 Heat-Shock Proteins
Estradiol
European Union
Epithelial Cells
NF-kappa B
Shock
Hot Temperature
Down-Regulation
I-kappa B Kinase
Equine Gonadotropins
Chorionic Gonadotropin
Fertilization in Vitro
Serum
Inbred C57BL Mouse
Immunoprecipitation
Small Interfering RNA
Phosphotransferases
Immunohistochemistry
Apoptosis
Antibodies

Keywords

  • Endometrial epithelial cell
  • Heat shock protein 70
  • High estradiol concentration
  • NF-κB

ASJC Scopus subject areas

  • Cell Biology

Cite this

High estradiol concentrations induce heat shock protein 70 expression and suppress nuclear factor kappa b activation in human endometrial epithelial cells. / Chen, Chin Der; Chen, Shee Uan; Chou, Chia Hung; Chen, Mei Jou; Wen, Wen Fen; Wu, Szu Yuan; Yang, Yu Shih; Yang, Jehn Hsiahn.

In: Biology of Reproduction, Vol. 95, No. 4, 87, 01.10.2016.

Research output: Contribution to journalArticle

Chen, Chin Der ; Chen, Shee Uan ; Chou, Chia Hung ; Chen, Mei Jou ; Wen, Wen Fen ; Wu, Szu Yuan ; Yang, Yu Shih ; Yang, Jehn Hsiahn. / High estradiol concentrations induce heat shock protein 70 expression and suppress nuclear factor kappa b activation in human endometrial epithelial cells. In: Biology of Reproduction. 2016 ; Vol. 95, No. 4.
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