Decidualized endometrial stromal cells present with altered androgen response in PCOS

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 pro...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Masuma Khatun, Alvin Meltsov, Darja Lavogina, Marina Loid, Keiu Kask, Riikka K. Arffman, Henna-Riikka Rossi, Freddy Lättekivi, Kersti Jääger, Kaarel Krjutškov, Ago Rinken, Andres Salumets, Terhi T. Piltonen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9dcc0bb266634d95ab67b30d78611c06
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:9dcc0bb266634d95ab67b30d78611c06
record_format	dspace
spelling	oai:doaj.org-article:9dcc0bb266634d95ab67b30d78611c062021-12-02T15:08:23ZDecidualized endometrial stromal cells present with altered androgen response in PCOS10.1038/s41598-021-95705-02045-2322https://doaj.org/article/9dcc0bb266634d95ab67b30d78611c062021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95705-0https://doaj.org/toc/2045-2322Abstract 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.Masuma KhatunAlvin MeltsovDarja LavoginaMarina LoidKeiu KaskRiikka K. ArffmanHenna-Riikka RossiFreddy LättekiviKersti JäägerKaarel KrjutškovAgo RinkenAndres SalumetsTerhi T. PiltonenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Masuma Khatun Alvin Meltsov Darja Lavogina Marina Loid Keiu Kask Riikka K. Arffman Henna-Riikka Rossi Freddy Lättekivi Kersti Jääger Kaarel Krjutškov Ago Rinken Andres Salumets Terhi T. Piltonen Decidualized endometrial stromal cells present with altered androgen response in PCOS
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.
format	article
author	Masuma Khatun Alvin Meltsov Darja Lavogina Marina Loid Keiu Kask Riikka K. Arffman Henna-Riikka Rossi Freddy Lättekivi Kersti Jääger Kaarel Krjutškov Ago Rinken Andres Salumets Terhi T. Piltonen
author_facet	Masuma Khatun Alvin Meltsov Darja Lavogina Marina Loid Keiu Kask Riikka K. Arffman Henna-Riikka Rossi Freddy Lättekivi Kersti Jääger Kaarel Krjutškov Ago Rinken Andres Salumets Terhi T. Piltonen
author_sort	Masuma Khatun
title	Decidualized endometrial stromal cells present with altered androgen response in PCOS
title_short	Decidualized endometrial stromal cells present with altered androgen response in PCOS
title_full	Decidualized endometrial stromal cells present with altered androgen response in PCOS
title_fullStr	Decidualized endometrial stromal cells present with altered androgen response in PCOS
title_full_unstemmed	Decidualized endometrial stromal cells present with altered androgen response in PCOS
title_sort	decidualized endometrial stromal cells present with altered androgen response in pcos
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9dcc0bb266634d95ab67b30d78611c06
work_keys_str_mv	AT masumakhatun decidualizedendometrialstromalcellspresentwithalteredandrogenresponseinpcos AT alvinmeltsov decidualizedendometrialstromalcellspresentwithalteredandrogenresponseinpcos AT darjalavogina decidualizedendometrialstromalcellspresentwithalteredandrogenresponseinpcos AT marinaloid decidualizedendometrialstromalcellspresentwithalteredandrogenresponseinpcos AT keiukask decidualizedendometrialstromalcellspresentwithalteredandrogenresponseinpcos AT riikkakarffman decidualizedendometrialstromalcellspresentwithalteredandrogenresponseinpcos AT hennariikkarossi decidualizedendometrialstromalcellspresentwithalteredandrogenresponseinpcos AT freddylattekivi decidualizedendometrialstromalcellspresentwithalteredandrogenresponseinpcos AT kerstijaager decidualizedendometrialstromalcellspresentwithalteredandrogenresponseinpcos AT kaarelkrjutskov decidualizedendometrialstromalcellspresentwithalteredandrogenresponseinpcos AT agorinken decidualizedendometrialstromalcellspresentwithalteredandrogenresponseinpcos AT andressalumets decidualizedendometrialstromalcellspresentwithalteredandrogenresponseinpcos AT terhitpiltonen decidualizedendometrialstromalcellspresentwithalteredandrogenresponseinpcos
_version_	1718388139628691456

Decidualized endometrial stromal cells present with altered androgen response in PCOS

Ejemplares similares