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Stretching, Mechanotransduction, and Proinflammatory Cytokines in the Fetal Membranes

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Abstract

In the third trimester of normal pregnancy, the human fetal membranes become increasingly distended and use mechanotransduction and its downstream signaling to remodel and function. Their overdistension either by multifetal pregnancy or by polyhydramnios often leads to preterm birth, but the mechanism is unclear. Stretching of the fetal membranes in vitro upregulates several cytokines and enzymes that can drive collagen degradation, leading to membrane rupture. The sensitivity of this response appears to be specific for different cell types and is likely to result from differential activation of some key transcription factors and cofactors. Few cytokines in the fetal membranes respond to stretch: the most robust of these is pre—B-cell colony-enhancing factor (PBEF). This is constitutively expressed and protects the amnion cells from apoptosis caused by chronic static distension. However, it can also be stimulated by inflammation, infection, and hypoxia and upregulates a number of proinflammatory cytokines, chemokines, and enzymes important in the initiation of parturition. Therefore, it is proposed here that PBEF functions in normal pregnancy to protect the amnion cells as they become increasingly stretched, but if stimulated, it can initiate key events leading to parturition.

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Authors and Affiliations

  1. Developmental and Reproductive Biology, John A. Burns School of Medicine, Pacific Biomedical Research Center, University of Hawaii, 651 Ilalo Street, Biosciences Building, Honolulu, HI, 96813, USA

    Claire E. Kendal-Wright PhD

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  1. Claire E. Kendal-Wright PhD
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Correspondence to Claire E. Kendal-Wright PhD.

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Supported by grants from the Hawaii Community Foundation (20041651 and 20061057) and the Research Centers in Minority Institutions Program of the National Institutes of Health (RRIA1-03061 and RR-11091). I thank Dr Gillian Bryant-Greenwood for her support and suggestions during the course of this work and acknowledge the expert technical assistance of Daniela Hubbard.

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Kendal-Wright, C.E. Stretching, Mechanotransduction, and Proinflammatory Cytokines in the Fetal Membranes. Reprod. Sci. 14 (Suppl 8), 35–41 (2007). https://doi.org/10.1177/1933719107310763

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