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Title: Metal induced bystander signalling between trophoblast cells and human embryonic stem cells
Author: Rogers, Anna Jayne
ISNI:       0000 0004 5349 7065
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2014
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Humans may be exposed to cobalt (Co) and chromium (Cr) ions through occupation in the metal industries or through the implantation of surgical devices made from cobalt-chrome alloy. Epidemiological studies have reported a significant excess of respiratory carcinoma in metal industry workers exposed to Cr-containing dusts and vapours. Cr6+ has thus been classified as a Class 1 compound- known to be carcinogenic to humans- by the International Agency for Research on Cancer (IARC). Co2+ has been classified as a Class 2b compound- possibly carcinogenic to humans. The potential teratogenic effects of Co2+ and Cr6+ are largely unknown. Animal experiments have demonstrated an increased risk of miscarriage and foetal malformation following maternal exposure to Co2+ or Cr6+ during pregnancy. Similarly, a recent meta-analysis has shown an association between maternal occupational Cr poisoning and risk of spontaneous abortion in humans. Here, an in vitro strategy was used to investigate the risks to an embryo from Co and Cr ions within the maternal circulation. To do this, human embryonic stem cells (hESCs) were exposed to Co2+ and Cr6+ across a model of the placenta barrier (a confluent bilayer of trophoblast cells) . This indirect exposure of hESCs to Co2+ and Cr6+ induced DNA damage and apoptosis in the hESC colonies. These damaging effects were not caused by the Co and Cr ions passing through the barrier. Instead, they were caused by the release of at least two bystander like signalling molecules (including TNF-a) from the trophoblast barrier. This signalling mechanism between the trophoblast barrier and the hESCs depends on gap junctional intercellular communication within the barrier and the hESC colonies. If translated into an in vivo response, the signalling mechanism uncovered here could imply a sensitive mechanism for miscarriage if the mother is exposed to a low dose of a toxin
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available