Decidualized Endometrial Stromal Cells Present with Altered Androgen Response in PCOS

Overview

Journal Sci Rep

Specialty Science

Date 2021 Aug 12

PMID 34381107

Citations 11

Authors

Masuma Khatun

Alvin Meltsov

Darja Lavogina

Marina Loid

Keiu Kask

Riikka K Arffman

Henna-Riikka Rossi

Freddy Lattekivi

Kersti Jaager

Kaarel Krjutskov

Ago Rinken

Andres Salumets

Terhi T Piltonen

Affiliations

Soon will be listed here.

Abstract

Hyperandrogenic women with PCOS show disrupted decidualization (DE) and placentation. Dihydrotestosterone (DHT) is reported to enhance DE in non-PCOS endometrial stromal cells (eSC); however, this has not been assessed in PCOS cells (eSC). 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 eSC 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 eSC, 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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