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Roles of Progesterone Receptor Membrane Component 1 in Oxidative Stress—Induced Aging in Chorion Cells

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Abstract

Introduction

Oxidative stress—mediated fetal membrane cell aging is activated prematurely in preterm premature rupture of membranes (PPROMs). The mechanism of this phenomenon is largely understudied. Progesterone receptor membrane component 1 (PGRMC1) has been recognized as a potential protective component for maintaining fetal membrane integrity and healthy pregnancies. We aimed to investigate the effects of oxidative stress (represented by hydrogen peroxide [H2O2]) on fetal membrane and chorion cell senescence, p38 mitogen-activated protein kinase (MAPK) phosphorylation, and sirtuin 3 (SIRT3) and to examine the roles of PGRMC1 in these effects.

Methods

Following serum starvation for 24 hours, full-thickness fetal membrane explants and primary chorion cells were treated with H2O2 at 100, 300, and 500 µM for 24 hours. Cells were fixed for cell senescence-associated β-galactosidase assay. Cell lysates were harvested for quantitive reverse transcription polymerase chain reaction to quantify SIRT3 messenger RNA. Cell lysates were harvested for Western blot to semi-quantify SIRT3 protein and p38 MAPK phosphorylation levels, respectively. To examine the role of PGRMC1, primary chorion cells underwent the same treatment mentioned above following PGRMC1 knockdown using validated PGRMC1-specific small-interfering RNA.

Results

Hydrogen peroxide significantly induced cell senescence and p38 MAPK phosphorylation, and it significantly decreased SIRT3 expression in full-thickness fetal membrane explants and chorion cells. These effects were enhanced by PGRMC1 knockdown.

Discussion

This study further demonstrated that oxidative stress—induced cell aging is one of the mechanisms of PPROM and PGRMC1 acts as a protective element for maintaining fetal membrane integrity by inhibiting oxidative stress—induced chorion cell aging.

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Authors and Affiliations

  1. Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Duke University Medical Center, Box 103208, Durham, NC, 27710, USA

    Liping Feng MD, William P. Marinello BS & Amy P. Murtha MD

  2. Ministry of Education and Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Liping Feng MD

  3. Department of Anesthesiology, Duke University, Durham, NC, USA

    Terrence K. Allen MBBS, FRCA

Authors
  1. Liping Feng MD
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  2. Terrence K. Allen MBBS, FRCA
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  3. William P. Marinello BS
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  4. Amy P. Murtha MD
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Correspondence to Liping Feng MD.

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Authors’ Note

Liping Feng designed the study, performed experiments, analyzed and interpreted the data, and prepared the manuscript. Terrence Allen participated in the statistical analysis and contributed to the manuscript preparation. William Marinello performed some of the experiments. Amy Murtha contributed to the study design and participated in manuscript preparation.

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Feng, L., Allen, T.K., Marinello, W.P. et al. Roles of Progesterone Receptor Membrane Component 1 in Oxidative Stress—Induced Aging in Chorion Cells. Reprod. Sci. 26, 394–403 (2019). https://doi.org/10.1177/1933719118776790

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