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Research Paper|Volume 11, Issue 21|pp 9912—9931

Molecular basis of senescence transmitting in the population of human endometrial stromal cells

Anastasiia Griukova1, Pavel Deryabin1, Alla Shatrova1, Elena Burova1, Valeria Severino2, Annarita Farina2, Nikolay Nikolsky1, Aleksandra Borodkina1
  • 1Department of Intracellular Signaling and Transport, Institute of Cytology of the Russian Academy of Sciences, Petersburg 194064, Russia
  • 2Department of Medicine, University Medical Center (CMU), Faculty of Medicine, Geneva University, Geneva CH-1211, Switzerland
* Equal contribution
Received: August 21, 2019Accepted: October 29, 2019Published: November 5, 2019
https://doi.org/10.18632/aging.102441

Copyright © 2019 Griukova et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Hormone-regulated proliferation and differentiation of endometrial stromal cells (ESCs) determine overall endometrial plasticity and receptivity to embryos. Previously we revealed that ESCs may undergo premature senescence, accompanied by proliferation loss and various intracellular alterations. Here we focused on whether and how senescence may be transmitted within the ESCs population. We revealed that senescent ESCs may induce paracrine senescence in young counterparts via cell contacts, secreted factors and extracellular vesicles. According to secretome-wide profiling we identified plasminogen activator inhibitor -1 (PAI-1) to be the most prominent protein secreted by senescent ESCs (data are available via ProteomeXchange with identifier PXD015742). By applying CRISPR/Cas9 techniques we disclosed that PAI-1 secreted by senescent ESCs may serve as the master-regulator of paracrine senescence progression within the ESCs population. Unraveled molecular basis of senescence transduction in the ESCs population may be further considered in terms of altered endometrial plasticity and sensitivity to invading embryo, thus contributing to the female infertility curing.