University of Oulu

Khatun, M., Meltsov, A., Lavogina, D. et al. Decidualized endometrial stromal cells present with altered androgen response in PCOS. Sci Rep 11, 16287 (2021). https://doi.org/10.1038/s41598-021-95705-0

Decidualized endometrial stromal cells present with altered androgen response in PCOS

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Author: Khatun, Masuma1; Meltsov, Alvin2,3; Lavogina, Darja2,4;
Organizations: 1Department of Obstetrics and Gynaecology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
2Competence Centre on Health Technologies, Tartu, Estonia
3Department of Computer Science, University of Tartu, Tartu, Estonia
4Institute of Chemistry, University of Tartu, Tartu, Estonia
5Department of Obstetrics and Gynaecology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia
6Department of Pathophysiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
7Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, Tartu, Estonia
8Division of Obstetrics and Gynaecology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 5.9 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021101250708
Language: English
Published: Springer Nature, 2021
Publish Date: 2021-10-12
Description:

Abstract

Hyperandrogenic women with PCOS show disrupted decidualization (DE) and placentation. Dihydrotestosterone (DHT) is reported to enhance DE in non-PCOS endometrial stromal cells (eSCCtrl); however, this has not been assessed in PCOS cells (eSCPCOS). Therefore, we studied the transcriptome profile of non-decidualized (non-DE) and DE eSCs from women with PCOS and Ctrl in response to short-term estradiol (E2) and/or progesterone (P4) exposure with/without (±) DHT. The non-DE eSCs were subjected to E2 ± DHT treatment, whereas the DE (0.5 mM 8-Br-cAMP, 96 h) eSCs were post-treated with E2 and P4 ± DHT, and RNA-sequenced. Validation was performed by immunofluorescence and immunohistochemistry. The results showed that, regardless of treatment, the PCOS and Ctrl samples clustered separately. The comparison of DE vs. non-DE eSCPCOS without DHT revealed PCOS-specific differentially expressed genes (DEGs) involved in mitochondrial function and progesterone signaling. When further adding DHT, we detected altered responses for lysophosphatidic acid (LPA), inflammation, and androgen signaling. Overall, the results highlight an underlying defect in decidualized eSCPCOS, present with or without DHT exposure, and possibly linked to the altered pregnancy outcomes. We also report novel factors which elucidate the mechanisms of endometrial dysfunction in PCOS.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 11
Issue: 1
Article number: 16287
DOI: 10.1038/s41598-021-95705-0
OADOI: https://oadoi.org/10.1038/s41598-021-95705-0
Type of Publication: A1 Journal article – refereed
Field of Science: 3123 Gynaecology and paediatrics
3111 Biomedicine
Subjects:
Funding: This work was financially supported by a grant from the Academy of Finland (grant no. 315921, 321763), the Finnish Medical Foundation, The Sigrid Juselius Foundation, Estonian Research Council (grant PRG1076), Horizon 2020 innovation (ERIN, grant no. EU952516) of the European Commission and Enterprise Estonia (grant EU48695).
Academy of Finland Grant Number: 315921
321763
Detailed Information: 315921 (Academy of Finland Funding decision)
321763 (Academy of Finland Funding decision)
Copyright information: © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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