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Frequency and function of lymphocytes in labouring compared to non-labouring decidua

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Title: Frequency and function of lymphocytes in labouring compared to non-labouring decidua
Authors: Whettlock, Emily
Item Type: Thesis or dissertation
Abstract: The uterine mucosa, known as the decidua during pregnancy, contains a unique immune microenvironment. Decidual immune activation has been hypothesised to initiate labour, the end of pregnancy when the muscles contract to excel the baby. Understanding this process could facilitate the development of medications to delay labour and prevent preterm birth. Prior research examining decidual immune cells during labour lacked known decidual markers. Single cell RNA sequencing (scRNAseq) data has provided more information about the uterine immune landscape e.g. identifying three uterine NK subsets (uNK1-3). Using existing scRNAseq data and novel flow cytometry data, I examined decidual immune cells during labour. I integrated existing uterine scRNAseq datasets, from throughout the reproductive cycle. The data showed the immune environment is dynamic, suggesting roles for particular cells at different stages e.g. uNKs in the first trimester. uNK1 were thought to aid placental implantation, due to their receptor expression profile. However, I noted an upregulation of these receptors in all uNK subsets in the first trimester, suggesting they are all involved. I optimised a protocol to isolate immune cells from term decidua. The scRNAseq and flow cytometry data suggests that uNKs and Tregs do not have a significant role initiating labour. My examination of an existing scRNAseq dataset found a cluster of chemokine producing myeloid cells which expanded in the decidua parietalis during labour. This, along with insights from rat models, suggests these myeloid cells are potential initiators of labour. The integrated analysis of uterine immune cells could be used as a guide for investigating abnormalities throughout the reproductive cycle. For the labouring data, uNK and Tregs have been excluded as having a large role in initiating term labour and myeloid cells put forward as potential candidates for this role. Also, this term data could guide future studies on preterm birth.
Content Version: Open Access
Issue Date: Jan-2023
Date Awarded: Oct-2023
URI: http://hdl.handle.net/10044/1/107752
DOI: https://doi.org/10.25560/107752
Copyright Statement: Creative Commons Attribution NonCommercial Licence
Supervisor: Male, Victoria
Johnson, Mark
Sponsor/Funder: Borne Foundation
Department: Department of Metabolism, Digestion and Reproduction
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:Department of Metabolism, Digestion and Reproduction PhD Theses



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