Endometrial regeneration and uterine disorders - cellular and molecular studies
Thesis event information
Date and time of the thesis defence
Place of the thesis defence
Lärosal David, Widerströmska huset, Tomtebodavägen 18a, Solna, Stockholm
Topic of the dissertation
Endometrial regeneration and uterine disorders - cellular and molecular studies
Doctoral candidate
Master of Clinical Medicine Yiqun Tang
Faculty and unit
University of Oulu Graduate School, Faculty of Medicine, University of Oulu Graduate School, Faculty of Medicine, Medical Research Center
Subject of study
Medicine
Opponent
Professor Stefan R. Hasson, Lund University
Custos
Professor Terhi Piltonen, University of Oulu
Healing the Uterus: Studying Cells and Molecules in Endometrial regeneration and Uterine Diseases
The human endometrium, a unique mucosal tissue, exhibits remarkable regenerative capacity, undergoing monthly cycles of breakdown and renewal. Such a dynamic remodeling process is hypothesized to be initiated and orchestrated by putative stem/progenitor cells residing in the basalis layer. However, precise characterization of these stem cell populations and their regulatory networks remains elusive due to limited access to full-thickness endometrial specimens and insufficient exploration of tissue heterogeneity at single-cell resolution. Many pathological factors can disrupt normal endometrial remodeling, leading to various common uterine disorders, including endometriosis, adenomyosis, intrauterine adhesions, and thin endometrium, therefore extensively affecting women’s reproductive health. Elucidating the spatial and temporal dynamics of endometrial tissue heterogeneity at single-cell resolution is therefore essential for understanding the cellular and molecular mechanisms governing endometrial regeneration, thereby enhancing our mechanistic insight into the pathogenesis of various uterine disorders and facilitating the development of more targeted therapeutics.
In Study I, we explored the therapeutic action of vaginal bromocriptine for adenomyosis. Our findings revealed that bromocriptine treatment exerted anti-proliferative effects on eutopic endometrium from adenomyosis both ex vivo and in vitro, potentially acting by regulating certain microRNAs and signaling pathways linked to cell proliferation.
In Study II, we investigated the role of microRNAs in endometriosis through small RNA sequencing. Comparative analysis between women with and without endometriosis identified 14 differentially expressed microRNAs. Through integrated analysis combining target gene prediction, mRNA sequencing, experimental validation, and bioinformatic analysis, we characterized two key microRNAs and their potential target genes that may contribute to endometriosis development through modulation of cell migration and relevant pathways.
In Study III, we analyzed transcriptional profiles of placental tissues from SARS-CoV-2 infected and non-infected women during the third trimester of pregnancy. Despite the absence of detectable viral load in placental tissue, we observed significant downregulation of nine immunoglobulin superfamily genes in the maternal compartment of actively infected cases, suggesting potential molecular mechanisms underlying the increased risks of pregnancy complications associated with COVID-19 infection.
In Study IV, utilizing high-resolution spatial transcriptomics (Visium HD), we mapped cellular heterogeneity within full-thickness endometrium across three distinct time points during the proliferative phase. Our results provide a highly resolved spatial transcriptional atlas of the proliferative endometrium that aligns well with tissue morphology, revealing pronounced spatial cellular heterogeneity and dynamic molecular change during endometrial regeneration.
In Study I, we explored the therapeutic action of vaginal bromocriptine for adenomyosis. Our findings revealed that bromocriptine treatment exerted anti-proliferative effects on eutopic endometrium from adenomyosis both ex vivo and in vitro, potentially acting by regulating certain microRNAs and signaling pathways linked to cell proliferation.
In Study II, we investigated the role of microRNAs in endometriosis through small RNA sequencing. Comparative analysis between women with and without endometriosis identified 14 differentially expressed microRNAs. Through integrated analysis combining target gene prediction, mRNA sequencing, experimental validation, and bioinformatic analysis, we characterized two key microRNAs and their potential target genes that may contribute to endometriosis development through modulation of cell migration and relevant pathways.
In Study III, we analyzed transcriptional profiles of placental tissues from SARS-CoV-2 infected and non-infected women during the third trimester of pregnancy. Despite the absence of detectable viral load in placental tissue, we observed significant downregulation of nine immunoglobulin superfamily genes in the maternal compartment of actively infected cases, suggesting potential molecular mechanisms underlying the increased risks of pregnancy complications associated with COVID-19 infection.
In Study IV, utilizing high-resolution spatial transcriptomics (Visium HD), we mapped cellular heterogeneity within full-thickness endometrium across three distinct time points during the proliferative phase. Our results provide a highly resolved spatial transcriptional atlas of the proliferative endometrium that aligns well with tissue morphology, revealing pronounced spatial cellular heterogeneity and dynamic molecular change during endometrial regeneration.
Last updated: 31.3.2025