Ryanodine receptor expression in trophoblasts
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E-thesis
Date
2013
Authors
Zheng, Limian
Journal Title
Journal ISSN
Volume Title
Publisher
University College Cork
Published Version
Abstract
Trophoblasts of the placenta are the frontline cells involved in communication
and exchange of materials between the mother and fetus. Within trophoblasts, calcium
signalling proteins are richly expressed. Intracellular free calcium ions are a key
second messenger, regulating various cellular activities. Transcellular Ca2+ transport
through trophoblasts is essential in fetal skeleton formation. Ryanodine receptors
(RyRs) are high conductance cation channels that mediate Ca2+ release from
intracellular stores to the cytoplasm. To date, the roles of RyRs in trophoblasts have
not been reported. By use of reverse transcription PCR and western blotting, the
current study revealed that RyRs are expressed in model trophoblast cell lines (BeWo
and JEG-3) and in human first trimester and term placental villi.
Immunohistochemistry of human placental sections indicated that both
syncytiotrophoblast and cytotrophoblast cell layers were positively stained by
antibodies recognising RyRs; likewise, expression of RyR isoforms was also revealed
in BeWo and JEG-3 cells by immunofluorescence microscopy. In addition, changes in
[Ca2+]i were observed in both BeWo and JEG-3 cells upon application of various RyR
agonists and antagonists, using fura-2 fluorescent videomicroscopy. Furthermore,
endogenous placental peptide hormones, namely angiotensin II, arginine vasopressin
and endothelin 1, were demonstrated to increase [Ca2+]i in BeWo cells, and such
increases were suppressed by RyR antagonists and by blockers of the corresponding
peptide hormone receptors. These findings indicate that 1) multiple RyR subtypes are
expressed in human trophoblasts; 2) functional RyRs in BeWo and JEG-3 cells
response to both RyR agonists and antagonists; 3) RyRs in BeWo cells mediate Ca2+
release from intracellular store in response to the indirect stimulation by endogenous
peptides. These observations suggest that RyR contributes to trophoblastic cellular
Ca2+ homeostasis; trophoblastic RyRs are also involved in the functional regulation of
human placenta by coupling to endogenous placental peptide-induced signalling
pathways.
Description
Keywords
Calcium , Ryanodine receptor , Trophoblast
Citation
Zheng, L. 2013. Ryanodine receptor expression in trophoblasts. PhD Thesis, University College Cork.