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Endoplasmic reticulum stress induced by oxidative stress in decidual cells: a possible mechanism of early pregnancy loss

Molecular Biology Reports volume 39, pages 9179–9186 (2012)Cite this article

Abstract

Early pregnancy loss (EPL) is one of the most common complications of human reproduction. Combined with our previous proteomic studies on villous and decidual tissues of EPL, we found that alterations of the proteins involved in oxidative stress (OS), unfolded protein response (UPR) and proteolysis presented a complex and dynamic interaction at the maternal-fetal interface. In the present study, we developed a cell model of OS using normal decidual cells to examine cell viability and expression levels of proteins related to endoplasmic reticulum stress (ER stress) and UPR. We found that glucose regulated protein 78 (GRP 78) and ubiquitinated proteins were significantly up-regulated in hydrogen peroxide (H2O2) treated decidual cells in a dose-dependent manner. Excessive OS could influence proper function of UPR by decreasing VCP in decidual cells, thereby leading to cell damage as well as inhibition of cell growth and activation of apoptosis. Furthermore, when pretreated with MG 132, a pharmacological inhibition of the proteasome, the H2O2 treated decidual cells became less viable and could not up-regulate the expression level of GRP 78 to resolve the protein-folding defects, which indicating that malfunction of UPR in decidual cells might aggravate the inhibitory effect of OS in decidual cells. The present results reveal that abnormal protein profiles associated with OS induced ER stress and malfunction of UPR might be involved in the development of EPL, and OS and ER stress are potential targets for pregnant care and prognosis in normal pregnancy and its disorders.

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Abbreviations

EPL:

Early pregnancy loss

ER:

Endoplasmic reticulum

ERAD:

ER-associated degradation

GRP 78:

Glucose regulated protein 78

H2O2 :

Hydrogen peroxide

OS:

Oxidative stress

ROS:

Reactive oxygen species

UPR:

Unfolded protein response

VCP:

Valosin-containing protein

(ATF6):

Activating transcription factor-6

(XBP-1):

X-box binding protein-1

UPS:

Ubiquitin–proteasome system

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Acknowledgments

This work was supported by the National Basic Research Program of China (2006CB504004 and 2006CB944006), the National Natural Science Foundation of China (30670789 and 30801243), the Key Research Program of Zhejiang Province, China (2006C13078) and the Fundamental Research Funds for the Central Universities of China.

Conflict of interest

The authors have no conflicts to declare in relation to the material reported in this manuscript.

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Affiliations

  1. Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou, 310006, Zhejiang, China

    Hui-Juan Gao, Yi-Min Zhu, Ai-Xia Liu, Min-Yue Dong, Min Jin & He-Feng Huang

  2. Women’s Reproductive Health Key Laboratory of Zhejiang Province, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Ai-Xia Liu, Min-Yue Dong & He-Feng Huang

  3. Department of Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China

    Jian-Zhong Sheng

  4. Department of Obstetrics and Gynecology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Wei-Hua He

Authors
  1. Hui-Juan Gao
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  2. Yi-Min Zhu
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  6. Min Jin
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  8. He-Feng Huang
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Correspondence to He-Feng Huang.

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Gao, HJ., Zhu, YM., He, WH. et al. Endoplasmic reticulum stress induced by oxidative stress in decidual cells: a possible mechanism of early pregnancy loss. Mol Biol Rep 39, 9179–9186 (2012). https://doi.org/10.1007/s11033-012-1790-x

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  • DOI: https://doi.org/10.1007/s11033-012-1790-x

Keywords

  • Early pregnancy loss
  • Decidual cells
  • Oxidative
  • Endoplasmic reticulum
  • Stress
  • Ubiquitin–proteasome response