Frequency and function of lymphocytes in labouring compared to non-labouring decidua
File(s)
Author(s)
Whettlock, Emily
Type
Thesis
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.
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.
Version
Open Access
Date Issued
2023-01
Date Awarded
2023-10
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Male, Victoria
Johnson, Mark
Sponsor
Borne Foundation
Publisher Department
Department of Metabolism, Digestion and Reproduction
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)