The endometrium in disease – studies on endometrial stem cells, polycystic ovary syndrome (PCOS), and stanniocalcin-1 (STC-1)

Thesis event information

Date and time of the thesis defence

Place of the thesis defence

Oulu University Hospital, auditorium L4. Remote access: https://oulu.zoom.us/j/68579787451

Topic of the dissertation

The endometrium in disease – studies on endometrial stem cells, polycystic ovary syndrome (PCOS), and stanniocalcin-1 (STC-1)

Doctoral candidate

Master of Science Masuma Khatun

Faculty and unit

University of Oulu Graduate School, Faculty of Medicine, PEDEGO

Subject of study

Medicine

Opponent

Professor Kristina Gemzell Danielsson, Karolinska Institute, Sweden

Custos

Professor Terhi T. Piltonen, Oulu University Hospital, University of Oulu

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The endometrium in disease – studies on endometrial stem cells, polycystic ovary syndrome (PCOS), and stanniocalcin-1 (STC-1)

The human endometrium, the inner lining of the uterus, has a unique regenerative capacity to secure an optimal environment for embryo implantation. Any alterations in endometrial cell signaling may lead to suboptimal endometrial milieu and function, evident in gynecological disorders such as irregular menstruation, endometriosis, endometrial cancer (EC), and polycystic ovary syndrome (PCOS).

Indeed, a main target for the study, the PCOS endometrium, displays several endometrial aberrations involving disrupted steroid hormone regulation, metabolic dysfunction, and inflammation. Accordingly, endometrial cell populations, including endometrial stromal cells (eSCs) and mesenchymal stem cells (eMSCs), were investigated for their properties related to endometrial regeneration. These populations were compared to bone marrow mesenchymal stem cells (bmMSCs), previously suggested to be involved in endometrial regeneration. Next, the steroid hormone-induced transcriptome profile of eSCs from women with PCOS (eSC-PCOS) was assessed. Finally, the expression of stanniocalcin-1 (STC-1), a pro-survival factor, was explored in women with PCOS or EC.

The studies revealed high proliferation and migration potential for bmMSCs and eMSCs, supporting their role in endometrial renewal. Moreover, a subtler cytokine profile in the endometrial cells compared to bmMSCs indicated immune tolerance, possibly facilitating embryo implantation. The transcriptome data of eSC-PCOS indicated impaired function, as an altered expression of genes involved in progesterone action, metabolism, mitochondrial function, and inflammation was noted. Importantly, this alteration was present even without androgen exposure, although androgen exposure promoted the differences even further compared to a non-PCOS control (eSC-Ctrl). Hypoxia-induced STC-1 response in eSC-PCOS was also tested, and blunted STC-1 expression was noted, indicating a diseased endometrium. Finally, the protective role of STC-1 was reinforced by the finding that high STC-1 expression is associated with favorable clinicopathological features in EC cases.

The findings emphasize the favorable properties of bmMSCs and eMSCs for endometrial renewal. Moreover, eSC-PCOS present with an altered gene expression profile and hypoxia-induced STC-1 expression that may contribute to a diseased endometrium in PCOS. Finally, high STC-1 expression is associated with a more beneficial EC profile.
Last updated: 26.11.2021