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Neuropeptide Y directly reduced apoptosis of granulosa cells, and the expression of NPY and its receptors in PCOS subjects

BACKGROUND: Most women with anovulatory infertility show polycystic ovarian syndrome (PCOS), and androgen excess is known as a key factor involved in pathogenicity of PCOS. However, the mechanism of follicular developmental arrest in PCOS is not completely understood. The reproductive function of Ne...

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Autores principales: Urata, Yoko, Salehi, Reza, Wyse, Brandon A., Jahangiri, Sahar, Librach, Clifford L., Tzeng, Chii-Ruey, Osuga, Yutaka, Tsang, Benjamin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10469470/
https://www.ncbi.nlm.nih.gov/pubmed/37653540
http://dx.doi.org/10.1186/s13048-023-01261-8
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author Urata, Yoko
Salehi, Reza
Wyse, Brandon A.
Jahangiri, Sahar
Librach, Clifford L.
Tzeng, Chii-Ruey
Osuga, Yutaka
Tsang, Benjamin
author_facet Urata, Yoko
Salehi, Reza
Wyse, Brandon A.
Jahangiri, Sahar
Librach, Clifford L.
Tzeng, Chii-Ruey
Osuga, Yutaka
Tsang, Benjamin
author_sort Urata, Yoko
collection PubMed
description BACKGROUND: Most women with anovulatory infertility show polycystic ovarian syndrome (PCOS), and androgen excess is known as a key factor involved in pathogenicity of PCOS. However, the mechanism of follicular developmental arrest in PCOS is not completely understood. The reproductive function of Neuropeptide Y (NPY) in the ovary during folliculogenesis was previously reported; NPY function in apoptosis and proliferation of granulosa cells (GCs) is follicular-stage dependent. The objective of this study was to investigate the role of NPY in ovarian follicular development and the pathogenesis of PCOS. METHODS: To simulate the PCOS phenotype using a rat model, 21-day old Sprague Dawley rats were implanted with dihydrotestosterone (DHT) capsule (83 µg/day) and euthanized after 28 days. mRNA and protein content of NPY and its receptors were assessed in GCs from DHT treated rats using RT-qPCR and Western blot, respectively. Proliferation and apoptosis of GCs was assessed using Ki67- and TUNEL assays. Finally, NPY levels were measured in human follicular fluid (FF) from matched PCOS and non-PCOS patients using ELISA. RESULTS: GCs from DHT treated rats (PCOS-GCs) contained significantly less NPY protein and Npy mRNA by 0.16- and 0.56-fold, respectively, and more NPY receptor type 2 and 5 protein by 2.21- and 3.17-fold, respectively, when compared to sham control. Addition of recombinant NPY to PCOS-GCs culture did not alter Ki67-positive but significantly decreased TUNEL-positive cells by 0.65-fold, but not to baseline levels. There was no significant difference in NPY levels in FF between PCOS and non-PCOS subjects. CONCLUSIONS: These results indicate that DHT modulates expression of NPY and its receptors, NPY decreases DHT-induced GCs apoptosis. That alterations in NPY’s function might be involved in follicular developmental failure of PCOS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-023-01261-8.
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spelling pubmed-104694702023-09-01 Neuropeptide Y directly reduced apoptosis of granulosa cells, and the expression of NPY and its receptors in PCOS subjects Urata, Yoko Salehi, Reza Wyse, Brandon A. Jahangiri, Sahar Librach, Clifford L. Tzeng, Chii-Ruey Osuga, Yutaka Tsang, Benjamin J Ovarian Res Research BACKGROUND: Most women with anovulatory infertility show polycystic ovarian syndrome (PCOS), and androgen excess is known as a key factor involved in pathogenicity of PCOS. However, the mechanism of follicular developmental arrest in PCOS is not completely understood. The reproductive function of Neuropeptide Y (NPY) in the ovary during folliculogenesis was previously reported; NPY function in apoptosis and proliferation of granulosa cells (GCs) is follicular-stage dependent. The objective of this study was to investigate the role of NPY in ovarian follicular development and the pathogenesis of PCOS. METHODS: To simulate the PCOS phenotype using a rat model, 21-day old Sprague Dawley rats were implanted with dihydrotestosterone (DHT) capsule (83 µg/day) and euthanized after 28 days. mRNA and protein content of NPY and its receptors were assessed in GCs from DHT treated rats using RT-qPCR and Western blot, respectively. Proliferation and apoptosis of GCs was assessed using Ki67- and TUNEL assays. Finally, NPY levels were measured in human follicular fluid (FF) from matched PCOS and non-PCOS patients using ELISA. RESULTS: GCs from DHT treated rats (PCOS-GCs) contained significantly less NPY protein and Npy mRNA by 0.16- and 0.56-fold, respectively, and more NPY receptor type 2 and 5 protein by 2.21- and 3.17-fold, respectively, when compared to sham control. Addition of recombinant NPY to PCOS-GCs culture did not alter Ki67-positive but significantly decreased TUNEL-positive cells by 0.65-fold, but not to baseline levels. There was no significant difference in NPY levels in FF between PCOS and non-PCOS subjects. CONCLUSIONS: These results indicate that DHT modulates expression of NPY and its receptors, NPY decreases DHT-induced GCs apoptosis. That alterations in NPY’s function might be involved in follicular developmental failure of PCOS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-023-01261-8. BioMed Central 2023-08-31 /pmc/articles/PMC10469470/ /pubmed/37653540 http://dx.doi.org/10.1186/s13048-023-01261-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access 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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Urata, Yoko
Salehi, Reza
Wyse, Brandon A.
Jahangiri, Sahar
Librach, Clifford L.
Tzeng, Chii-Ruey
Osuga, Yutaka
Tsang, Benjamin
Neuropeptide Y directly reduced apoptosis of granulosa cells, and the expression of NPY and its receptors in PCOS subjects
title Neuropeptide Y directly reduced apoptosis of granulosa cells, and the expression of NPY and its receptors in PCOS subjects
title_full Neuropeptide Y directly reduced apoptosis of granulosa cells, and the expression of NPY and its receptors in PCOS subjects
title_fullStr Neuropeptide Y directly reduced apoptosis of granulosa cells, and the expression of NPY and its receptors in PCOS subjects
title_full_unstemmed Neuropeptide Y directly reduced apoptosis of granulosa cells, and the expression of NPY and its receptors in PCOS subjects
title_short Neuropeptide Y directly reduced apoptosis of granulosa cells, and the expression of NPY and its receptors in PCOS subjects
title_sort neuropeptide y directly reduced apoptosis of granulosa cells, and the expression of npy and its receptors in pcos subjects
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10469470/
https://www.ncbi.nlm.nih.gov/pubmed/37653540
http://dx.doi.org/10.1186/s13048-023-01261-8
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