GnRHa protects the ovarian reserve by reducing endoplasmic reticulum stress during cyclophosphamide-based chemotherapy

Abstract Chemotherapy-induced ovarian dysfunction is a serious adverse effect in premenopausal patients with cancer. Gonadotrophin-releasing hormone analogs (GnRHa) protect ovarian function, but its molecular mechanisms have not yet been determined. In this study, we attempted to determine the previ...

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Autores principales:	Xiaolin Li, Sixuan Liu, Xuan Chen, Run Huang, Lisi Ma, Huaiyu Weng, Yang Yu, Xiangyun Zong
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/5f42003b8ee944e89ba1d69d78f71cb5
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spelling	oai:doaj.org-article:5f42003b8ee944e89ba1d69d78f71cb52021-12-02T17:13:23ZGnRHa protects the ovarian reserve by reducing endoplasmic reticulum stress during cyclophosphamide-based chemotherapy10.1038/s41523-021-00340-72374-4677https://doaj.org/article/5f42003b8ee944e89ba1d69d78f71cb52021-10-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00340-7https://doaj.org/toc/2374-4677Abstract Chemotherapy-induced ovarian dysfunction is a serious adverse effect in premenopausal patients with cancer. Gonadotrophin-releasing hormone analogs (GnRHa) protect ovarian function, but its molecular mechanisms have not yet been determined. In this study, we attempted to determine the previously unknown molecular mechanism by which such protection occurs. Serum anti-Müllerian hormone (AMH) levels were tested in tumor-bearing nude mice, a series of exploratory experiments were conducted. We discovered that GnRHa protects granulosa cells from chemotherapeutic toxicity in vivo and in vitro. We also showed that CTX-induced endoplasmic reticulum stress inhibits the secretion of AMH, and treatment with GnRHa relieves ER stress and the subsequent unfolded-protein response by modulating mTOR signaling to induce autophagy. The results of mechanistic studies indicated that GnRHa-modulated mTOR signaling to induce autophagy, which alleviated CTX-induced ER stress and promoted the secretion of AMH.Xiaolin LiSixuan LiuXuan ChenRun HuangLisi MaHuaiyu WengYang YuXiangyun ZongNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Xiaolin Li Sixuan Liu Xuan Chen Run Huang Lisi Ma Huaiyu Weng Yang Yu Xiangyun Zong GnRHa protects the ovarian reserve by reducing endoplasmic reticulum stress during cyclophosphamide-based chemotherapy
description	Abstract Chemotherapy-induced ovarian dysfunction is a serious adverse effect in premenopausal patients with cancer. Gonadotrophin-releasing hormone analogs (GnRHa) protect ovarian function, but its molecular mechanisms have not yet been determined. In this study, we attempted to determine the previously unknown molecular mechanism by which such protection occurs. Serum anti-Müllerian hormone (AMH) levels were tested in tumor-bearing nude mice, a series of exploratory experiments were conducted. We discovered that GnRHa protects granulosa cells from chemotherapeutic toxicity in vivo and in vitro. We also showed that CTX-induced endoplasmic reticulum stress inhibits the secretion of AMH, and treatment with GnRHa relieves ER stress and the subsequent unfolded-protein response by modulating mTOR signaling to induce autophagy. The results of mechanistic studies indicated that GnRHa-modulated mTOR signaling to induce autophagy, which alleviated CTX-induced ER stress and promoted the secretion of AMH.
format	article
author	Xiaolin Li Sixuan Liu Xuan Chen Run Huang Lisi Ma Huaiyu Weng Yang Yu Xiangyun Zong
author_facet	Xiaolin Li Sixuan Liu Xuan Chen Run Huang Lisi Ma Huaiyu Weng Yang Yu Xiangyun Zong
author_sort	Xiaolin Li
title	GnRHa protects the ovarian reserve by reducing endoplasmic reticulum stress during cyclophosphamide-based chemotherapy
title_short	GnRHa protects the ovarian reserve by reducing endoplasmic reticulum stress during cyclophosphamide-based chemotherapy
title_full	GnRHa protects the ovarian reserve by reducing endoplasmic reticulum stress during cyclophosphamide-based chemotherapy
title_fullStr	GnRHa protects the ovarian reserve by reducing endoplasmic reticulum stress during cyclophosphamide-based chemotherapy
title_full_unstemmed	GnRHa protects the ovarian reserve by reducing endoplasmic reticulum stress during cyclophosphamide-based chemotherapy
title_sort	gnrha protects the ovarian reserve by reducing endoplasmic reticulum stress during cyclophosphamide-based chemotherapy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5f42003b8ee944e89ba1d69d78f71cb5
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GnRHa protects the ovarian reserve by reducing endoplasmic reticulum stress during cyclophosphamide-based chemotherapy

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