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Oxford University Press, Biology of Reproduction, 3(91), 2014

DOI: 10.1095/biolreprod.114.120741

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Endoplasmic Reticulum Stress Is Increased after Spontaneous Labor in Human Fetal Membranes and Myometrium Where It Regulates the Expression of Prolabor Mediators1

Journal article published in 2014 by Stella Liong ORCID, Martha Lappas
This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Data provided by SHERPA/RoMEO

Abstract

Increasing evidence indicates that endoplasmic reticulum (ER) stress is involved in various diseases. In non-gestational tissues, several markers of the unfolded protein response (UPR) have been shown to regulate the inflammatory response. Thus, the aim of this study was to determine the effect of human labour on markers of ER stress in fetal membranes and myometrium. In addition, the effect of ER stress inhibition on the expression and secretion of pro-inflammatory and pro-labour mediators was also assessed. The markers of ER stress, GRP78, IRE1 and spliced XBP1 (XBP1s), were significantly increased in fetal membranes and myometrium after term and preterm labor compared to non-laboring samples. Given that inflammation is considered to be one of the leading causes of spontaneous preterm birth, here we used bacterial endotoxin lipopolysaccharide (LPS) as a model for infection-induced preterm birth. In term non-labored fetal membranes and myometrium, LPS induced UPR activation as evidenced by a significant increase in the expression of GRP78, IRE1 and XBP1s in fetal membranes and myometrium. The use of the chemical chaperones 4-phenylbutyric acid (4-PBA) and tauroursodeoxycholic acid (TUDCA) alleviated ER stress induced by LPS. 4-PBA and TUDCA also ameliorated the increase in LPS-induced pro-labor mediators. Our data suggests that the UPR may regulate the inflammatory responses associated with labor or infection in fetal membranes and myometrium of pregnant term and preterm women. Thus, the use of ER stress inhibitors, in particular 4-PBA or TUDCA, may be a potential therapeutic strategy for the prevention of infection-mediated spontaneous preterm birth.