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Decidualized endometrial stromal cells present with altered androgen response in PCOS.
Khatun, Masuma; Meltsov, Alvin; Lavogina, Darja; Loid, Marina; Kask, Keiu; Arffman, Riikka K; Rossi, Henna-Riikka; Lättekivi, Freddy; Jääger, Kersti; Krjutskov, Kaarel; Rinken, Ago; Salumets, Andres; Piltonen, Terhi T.
Afiliação
  • Khatun M; Department of Obstetrics and Gynaecology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland.
  • Meltsov A; Competence Centre on Health Technologies, Tartu, Estonia.
  • Lavogina D; Department of Computer Science, University of Tartu, Tartu, Estonia.
  • Loid M; Competence Centre on Health Technologies, Tartu, Estonia.
  • Kask K; Institute of Chemistry, University of Tartu, Tartu, Estonia.
  • Arffman RK; Competence Centre on Health Technologies, Tartu, Estonia.
  • Rossi HR; Department of Obstetrics and Gynaecology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
  • Lättekivi F; Competence Centre on Health Technologies, Tartu, Estonia.
  • Jääger K; Department of Obstetrics and Gynaecology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
  • Krjutskov K; Department of Obstetrics and Gynaecology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland.
  • Rinken A; Department of Obstetrics and Gynaecology, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland.
  • Salumets A; Department of Pathophysiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
  • Piltonen TT; Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, Tartu, Estonia.
Sci Rep ; 11(1): 16287, 2021 08 11.
Article em En | MEDLINE | ID: mdl-34381107
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Síndrome do Ovário Policístico / Células Estromais / Endométrio / Androgênios Limite: Adult / Female / Humans / Pregnancy Idioma: En Revista: Sci Rep Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Finlândia

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Síndrome do Ovário Policístico / Células Estromais / Endométrio / Androgênios Limite: Adult / Female / Humans / Pregnancy Idioma: En Revista: Sci Rep Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Finlândia