Autoimmune thyroid disease disrupts immune homeostasis in the endometrium of unexplained infertility women—a single-cell RNA transcriptome study during the implantation window

ObjectiveAutoimmune thyroid disease (AITD) is known to be associated with unexplained infertility in women. Although the presence of antithyroid antibodies have been speculated to be a marker of an immune imbalance that might lead to implantation failure, its underlying mechanism influencing the end...

Full description

Bibliographic Details
Main Authors: Jilai Xie, Aiyuan Gu, Huangyi He, Qiaohang Zhao, Ya Yu, Jian Chen, Zhangliang Cheng, Ping Zhou, Qi Zhou, Min Jin
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-07-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2023.1185147/full
_version_ 1797782155458248704
author Jilai Xie
Aiyuan Gu
Huangyi He
Qiaohang Zhao
Ya Yu
Jian Chen
Zhangliang Cheng
Ping Zhou
Qi Zhou
Qi Zhou
Qi Zhou
Min Jin
author_facet Jilai Xie
Aiyuan Gu
Huangyi He
Qiaohang Zhao
Ya Yu
Jian Chen
Zhangliang Cheng
Ping Zhou
Qi Zhou
Qi Zhou
Qi Zhou
Min Jin
author_sort Jilai Xie
collection DOAJ
description ObjectiveAutoimmune thyroid disease (AITD) is known to be associated with unexplained infertility in women. Although the presence of antithyroid antibodies have been speculated to be a marker of an immune imbalance that might lead to implantation failure, its underlying mechanism influencing the endometrial receptivity remains to be elucidated. In this study, we used single-cell RNA sequencing (scRNA-seq) to dissect immune microenvironment in endometrium of AITD patients during window of implantation (WOI).MethodsWe collected CD45+ immune cell populations of endometrium samples of unexplained infertile women with AITD (n=3), as well as samples of AITD- controls (n=3). The cells were then processed with 10X Genomics Chromium for further analysis.ResultsWe characterized 28 distinct immune cell subtypes totally, and uncovered differences in the composition and gene expression patterns between AITD patients and controls. The proportions of T CD4+, cNK, ILC3, T CD8+GZMK+, T CD8+ Cytotoxic and ILC3 CD3E- cells were increased, and CD366+ uNK1 was decreased in AITD+ patients. And the abnormal expression of GNLY and chemokines was observed in AITD patients. In addition, uNK and T CD8+ Cytotoxic cells showed lower cytotoxicity but activation of immune response. Genes enriched in cell adhesion of ILC3 and Tregs were downregulated, while the number of ILC3 and Tregs were increased.ConclusionImmune imbalance exists in endometrium during WOI, which may impact embryo implantation.
first_indexed 2024-03-13T00:07:01Z
format Article
id doaj.art-aa3886c723694167a940a06c8185ef0e
institution Directory Open Access Journal
issn 1664-2392
language English
last_indexed 2024-03-13T00:07:01Z
publishDate 2023-07-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Endocrinology
spelling doaj.art-aa3886c723694167a940a06c8185ef0e2023-07-12T23:24:30ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-07-011410.3389/fendo.2023.11851471185147Autoimmune thyroid disease disrupts immune homeostasis in the endometrium of unexplained infertility women—a single-cell RNA transcriptome study during the implantation windowJilai Xie0Aiyuan Gu1Huangyi He2Qiaohang Zhao3Ya Yu4Jian Chen5Zhangliang Cheng6Ping Zhou7Qi Zhou8Qi Zhou9Qi Zhou10Min Jin11Second Affiliated Hospital, School of Medicine, Zhejiang University, Department of Reproductive Medicine, Hangzhou, ChinaMinistry of Education (MOE) Laboratory of Biosystems Homeostasis & Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, ChinaMinistry of Education (MOE) Laboratory of Biosystems Homeostasis & Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, ChinaSecond Affiliated Hospital, School of Medicine, Zhejiang University, Department of Reproductive Medicine, Hangzhou, ChinaSecond Affiliated Hospital, School of Medicine, Zhejiang University, Department of Reproductive Medicine, Hangzhou, ChinaSecond Affiliated Hospital, School of Medicine, Zhejiang University, Department of Reproductive Medicine, Hangzhou, ChinaMinistry of Education (MOE) Laboratory of Biosystems Homeostasis & Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, ChinaSecond Affiliated Hospital, School of Medicine, Zhejiang University, Department of Reproductive Medicine, Hangzhou, ChinaSecond Affiliated Hospital, School of Medicine, Zhejiang University, Department of Reproductive Medicine, Hangzhou, ChinaMinistry of Education (MOE) Laboratory of Biosystems Homeostasis & Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, ChinaDepartment of Neuroscience and Developmental Biology, University of Vienna, Vienna, AustriaSecond Affiliated Hospital, School of Medicine, Zhejiang University, Department of Reproductive Medicine, Hangzhou, ChinaObjectiveAutoimmune thyroid disease (AITD) is known to be associated with unexplained infertility in women. Although the presence of antithyroid antibodies have been speculated to be a marker of an immune imbalance that might lead to implantation failure, its underlying mechanism influencing the endometrial receptivity remains to be elucidated. In this study, we used single-cell RNA sequencing (scRNA-seq) to dissect immune microenvironment in endometrium of AITD patients during window of implantation (WOI).MethodsWe collected CD45+ immune cell populations of endometrium samples of unexplained infertile women with AITD (n=3), as well as samples of AITD- controls (n=3). The cells were then processed with 10X Genomics Chromium for further analysis.ResultsWe characterized 28 distinct immune cell subtypes totally, and uncovered differences in the composition and gene expression patterns between AITD patients and controls. The proportions of T CD4+, cNK, ILC3, T CD8+GZMK+, T CD8+ Cytotoxic and ILC3 CD3E- cells were increased, and CD366+ uNK1 was decreased in AITD+ patients. And the abnormal expression of GNLY and chemokines was observed in AITD patients. In addition, uNK and T CD8+ Cytotoxic cells showed lower cytotoxicity but activation of immune response. Genes enriched in cell adhesion of ILC3 and Tregs were downregulated, while the number of ILC3 and Tregs were increased.ConclusionImmune imbalance exists in endometrium during WOI, which may impact embryo implantation.https://www.frontiersin.org/articles/10.3389/fendo.2023.1185147/fullautoimmune thyroid diseaseunexplained infertilityendometrial receptivitywindow of implantationsingle-cell RNA sequencing
spellingShingle Jilai Xie
Aiyuan Gu
Huangyi He
Qiaohang Zhao
Ya Yu
Jian Chen
Zhangliang Cheng
Ping Zhou
Qi Zhou
Qi Zhou
Qi Zhou
Min Jin
Autoimmune thyroid disease disrupts immune homeostasis in the endometrium of unexplained infertility women—a single-cell RNA transcriptome study during the implantation window
Frontiers in Endocrinology
autoimmune thyroid disease
unexplained infertility
endometrial receptivity
window of implantation
single-cell RNA sequencing
title Autoimmune thyroid disease disrupts immune homeostasis in the endometrium of unexplained infertility women—a single-cell RNA transcriptome study during the implantation window
title_full Autoimmune thyroid disease disrupts immune homeostasis in the endometrium of unexplained infertility women—a single-cell RNA transcriptome study during the implantation window
title_fullStr Autoimmune thyroid disease disrupts immune homeostasis in the endometrium of unexplained infertility women—a single-cell RNA transcriptome study during the implantation window
title_full_unstemmed Autoimmune thyroid disease disrupts immune homeostasis in the endometrium of unexplained infertility women—a single-cell RNA transcriptome study during the implantation window
title_short Autoimmune thyroid disease disrupts immune homeostasis in the endometrium of unexplained infertility women—a single-cell RNA transcriptome study during the implantation window
title_sort autoimmune thyroid disease disrupts immune homeostasis in the endometrium of unexplained infertility women a single cell rna transcriptome study during the implantation window
topic autoimmune thyroid disease
unexplained infertility
endometrial receptivity
window of implantation
single-cell RNA sequencing
url https://www.frontiersin.org/articles/10.3389/fendo.2023.1185147/full
work_keys_str_mv AT jilaixie autoimmunethyroiddiseasedisruptsimmunehomeostasisintheendometriumofunexplainedinfertilitywomenasinglecellrnatranscriptomestudyduringtheimplantationwindow
AT aiyuangu autoimmunethyroiddiseasedisruptsimmunehomeostasisintheendometriumofunexplainedinfertilitywomenasinglecellrnatranscriptomestudyduringtheimplantationwindow
AT huangyihe autoimmunethyroiddiseasedisruptsimmunehomeostasisintheendometriumofunexplainedinfertilitywomenasinglecellrnatranscriptomestudyduringtheimplantationwindow
AT qiaohangzhao autoimmunethyroiddiseasedisruptsimmunehomeostasisintheendometriumofunexplainedinfertilitywomenasinglecellrnatranscriptomestudyduringtheimplantationwindow
AT yayu autoimmunethyroiddiseasedisruptsimmunehomeostasisintheendometriumofunexplainedinfertilitywomenasinglecellrnatranscriptomestudyduringtheimplantationwindow
AT jianchen autoimmunethyroiddiseasedisruptsimmunehomeostasisintheendometriumofunexplainedinfertilitywomenasinglecellrnatranscriptomestudyduringtheimplantationwindow
AT zhangliangcheng autoimmunethyroiddiseasedisruptsimmunehomeostasisintheendometriumofunexplainedinfertilitywomenasinglecellrnatranscriptomestudyduringtheimplantationwindow
AT pingzhou autoimmunethyroiddiseasedisruptsimmunehomeostasisintheendometriumofunexplainedinfertilitywomenasinglecellrnatranscriptomestudyduringtheimplantationwindow
AT qizhou autoimmunethyroiddiseasedisruptsimmunehomeostasisintheendometriumofunexplainedinfertilitywomenasinglecellrnatranscriptomestudyduringtheimplantationwindow
AT qizhou autoimmunethyroiddiseasedisruptsimmunehomeostasisintheendometriumofunexplainedinfertilitywomenasinglecellrnatranscriptomestudyduringtheimplantationwindow
AT qizhou autoimmunethyroiddiseasedisruptsimmunehomeostasisintheendometriumofunexplainedinfertilitywomenasinglecellrnatranscriptomestudyduringtheimplantationwindow
AT minjin autoimmunethyroiddiseasedisruptsimmunehomeostasisintheendometriumofunexplainedinfertilitywomenasinglecellrnatranscriptomestudyduringtheimplantationwindow