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The Human Fetal Membranes: A Versatile Tissue Important for Pregnancy Health and Regenerative Therapies

Special Issue Editors


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Guest Editor
Natural Science and Mathematics, Chaminade University of Honolulu, Honolulu, HI 96816, USA
Interests: human fetal membranes

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Guest Editor
Department of Obstetrics & Gynecology, Division of Basic and Translational Research, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
Interests: fetal inflammation

Special Issue Information

Dear Colleagues,

The human fetal membranes are an important but understudied gestational tissue. They are key for the health of the developing fetus, providing both mechanical and immune protection, along with a large surface area for fetal-to-maternal communication during pregnancy. Although physiologic labor-related signaling cascades induce ruptures at term, premature rupture of the membranes can contribute to Preterm birth onset. Preterm birth, along with other adverse pregnancy outcomes, remain the leading cause of infant mortality and morbidity globally. Premature rupture of membranes also contributes to the high rates of preterm birth by precipitating preterm labor or by increasing the vulnerability of the fetus to ascending infection.

This special edition focuses on both the fundamental molecular basis of its strength, development, and the pathological mechanism(s) leading to adverse pregnancy outcomes. It has solicited papers that discuss the molecular cascades that induce its weakening leading to rupture in both normal-term pregnancies and those that terminate prematurely in preterm birth. Due to the privileged properties of the cells of this tissue, it is also studied by researchers in various regenerative surgical and stem cell-driven therapies (i.e., ulcers, burn wounds, surgical scars). Thus, a wide range of papers focused on the key molecular mechanisms important to this tissue were welcomed with the aim to increase our understanding of the versatility of this tissue from several fields of biomedicine.

Dr. Claire E. Kendal-Wright
Dr. Lauren Richardson
Guest Editors

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Keywords

  • fetal membranes
  • tissue strength
  • inflammation
  • parturition
  • preterm premmature rupture of the membrane (PPROM)
  • infection
  • stem cells
  • regenerative surgery

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Published Papers (1 paper)

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Research

17 pages, 3794 KiB  
Article
Stretch Causes cffDNA and HMGB1-Mediated Inflammation and Cellular Stress in Human Fetal Membranes
by Justin Gary Padron, Chelsea A. Saito Reis, Po’okela K. Ng, Nainoa D. Norman Ing, Hannah Baker, Kamalei Davis, Courtney Kurashima and Claire E. Kendal-Wright
Int. J. Mol. Sci. 2024, 25(10), 5161; https://doi.org/10.3390/ijms25105161 - 9 May 2024
Viewed by 910
Abstract
Danger-associated molecular patterns (DAMPs) are elevated within the amniotic cavity, and their increases correlate with advancing gestational age, chorioamnionitis, and labor. Although the specific triggers for their release in utero remain unclear, it is thought that they may contribute to the initiation of [...] Read more.
Danger-associated molecular patterns (DAMPs) are elevated within the amniotic cavity, and their increases correlate with advancing gestational age, chorioamnionitis, and labor. Although the specific triggers for their release in utero remain unclear, it is thought that they may contribute to the initiation of parturition by influencing cellular stress mechanisms that make the fetal membranes (FMs) more susceptible to rupture. DAMPs induce inflammation in many different tissue types. Indeed, they precipitate the subsequent release of several proinflammatory cytokines that are known to be key for the weakening of FMs. Previously, we have shown that in vitro stretch of human amnion epithelial cells (hAECs) induces a cellular stress response that increases high-mobility group box-1 (HMGB1) secretion. We have also shown that cell-free fetal DNA (cffDNA) induces a cytokine response in FM explants that is fetal sex-specific. Therefore, the aim of this work was to further investigate the link between stretch and the DAMPs HMGB1 and cffDNA in the FM. These data show that stretch increases the level of cffDNA released from hAECs. It also confirms the importance of the sex of the fetus by demonstrating that female cffDNA induced more cellular stress than male fetuses. Our data treating hAECs and human amnion mesenchymal cells with HMGB1 show that it has a differential effect on the ability of the cells of the amnion to upregulate the proinflammatory cytokines and propagate a proinflammatory signal through the FM that may weaken it. Finally, our data show that sulforaphane (SFN), a potent activator of Nrf2, is able to mitigate the proinflammatory effects of stretch by decreasing the levels of HMGB1 release and ROS generation after stretch and modulating the increase of key cytokines after cell stress. HMGB1 and cffDNA are two of the few DAMPs that are known to induce cytokine release and matrix metalloproteinase (MMP) activation in the FMs; thus, these data support the general thesis that they can function as potential central players in the normal mechanisms of FM weakening during the normal distension of this tissue at the end of a normal pregnancy. Full article
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