Dirir, Ayan (2019) The role of phospholipase C Like 1 in the maintenance of uterine quiescence during human pregnancy. PhD thesis, University of Warwick.

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Abstract

With the rising rates of preterm birth, an in-depth understanding of the molecular mechanisms that govern preterm labour and uterine quiescence is needed, as this may lead to identifying drug targets that can prevent preterm labour or lead to reliable tests that identify those are at risk for premature labour. This thesis, focuses on Phospholipase C like-1 (PLCL-1). PLCL-1 is a protein that is similar in structure to PLC-δ1, however PLCL-1 is catalytically inactive. PLCL-1 has been shown to be downregulated in the myometrium of woman that are in labour compared to those that are not, this suggests a possible role for PLCL-1 in uterine quiescence and exploring the role PLCL-1 plays in uterine quiescence might explain one molecular pathway that leads to parturition. Calcium imaging disclosed that PLCL-1 reduced IP3 mediated calcium release in primary myometrial cells. Western blotting and RT-PCR illustrated that PLCL-1 transcription is induced by progesterone, this indicates that PLCL-1 is a progesterone responsive gene. High-throughput RNA sequencing showed that a loss in PLCL-1 resulted in an increase in phosphodiesterases, this led to a reduction in the levels of the pro-quiescent molecule: cAMP. In conclusion, this thesis demonstrates that PLCL-1 is downregulated in the labouring myometrium because it functions as a pro-quiescent protein, and its loss might lead to an increase in contractility.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	R Medicine > RG Gynecology and obstetrics
Library of Congress Subject Headings (LCSH):	Phospholipase C, Labor (Obstetrics) -- Endocrine aspects, Myometrium, Pregnancy -- Complications
Official Date:	February 2019
Dates:	Date Event February 2019 UNSPECIFIED
Institution:	University of Warwick
Theses Department:	Warwick Medical School
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Blanks, Andrew M.
Sponsors:	Grace Research Fund
Format of File:	pdf
Extent:	vi, 271 leaves : illustrations (mostly colour), charts
Language:	eng

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