FRI393 Mapping Endometrial Cell-type-specific Disease Signatures A nd Endometrial Organoids In Polycystic Ovary Syndrome

• Published in: Journal of the Endocrine Society 2023-10, Vol.7 (Supplement_1)
• Main Authors: Eriksson, Gustaw, Li, Congru, Risal, Sanjiv, Pui, Han-Pin, Torstensson, Sara, Hirschberg, Angelica Linden, Petropoulos, Sophie, Deng, Qiaolin, Stener-Victorin, Elisabet
• Format: Article
• Language: English
• Subjects: Reproductive Endocrinology
• ISSN: 2472-1972; 2472-1972
• DOI: 10.1210/jendso/bvad114.1587

Disclosure: G. Eriksson: None. C. Li: None. S. Risal: None. H. Pui: None. S. Torstensson: None. A. Linden Hirschberg: None. S. Petropoulos: None. Q. Deng: None. E. Stener-Victorin: None. Women with polycystic ovary syndrome (PCOS) suffer from reduced fertility linked to implantation failure and miscarriage, as well as endometrial cancer, all associated with endometrial dysfunction. We hypothesize that cell-type-specific endometrial dysfunction in insulin-resistant and hyperandrogenic women with PCOS contributes to the observed endometrial dysfunction and that treatment aimed at improving insulin sensitivity and decreasing androgen excess has the potential to reverse identified alterations.To uncover cell-type-specific disease signatures and molecular pathways for PCOS-specific endometrial dysfunction, we first extracted single-nuclei (sn) from frozen endometrial biopsies taken in the proliferative phase (day 7-10) from controls (n=5) and women with PCOS (n=10) at baseline and in PCOS after 16 weeks of metformin (n=7) or lifestyle management (n=3) for snRNA-sequencing. The 10x Genomics protocol allowed us to sequence ≈10,000 nuclei/sample and ≈20,000 reads/nuclei. A total of 248,694 nuclei were captured and 6 major cell types were identified. The 3 largest cell clusters were i) stromal cells (124,055 nuclei), ii) epithelial cells (105,095 nuclei) and iii) immune cells (13,596), whilst iv) uterine smooth muscle cells, v) endothelial and vi) lymphoid cell clusters consisted of