Chromatin Accessibility and Transcriptomic Alterations in Murine Ovarian Granulosa Cells upon Deoxynivalenol Exposure

Deoxynivalenol (DON) is a common environmental toxin that is secreted by fusarium fungi that frequently contaminates feedstuff and food. While the detrimental effects of DON on human and animal reproductive systems have been well recognized, the underlying mechanism remains poorly understood. Ovaria...

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Autores principales:	Hairui Fan, Zhanshi Ren, Chao Xu, Haifei Wang, Zhengchang Wu, Zia ur Rehman, Shenglong Wu, Ming-an Sun, Wenbin Bao
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ovarian granulosa cells mycotoxin chromatin accessibility gene expression cytotoxicity Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/549d3028d7c4412681059a4d8b72b4bd
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spelling	oai:doaj.org-article:549d3028d7c4412681059a4d8b72b4bd2021-11-25T17:07:32ZChromatin Accessibility and Transcriptomic Alterations in Murine Ovarian Granulosa Cells upon Deoxynivalenol Exposure10.3390/cells101128182073-4409https://doaj.org/article/549d3028d7c4412681059a4d8b72b4bd2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2818https://doaj.org/toc/2073-4409Deoxynivalenol (DON) is a common environmental toxin that is secreted by fusarium fungi that frequently contaminates feedstuff and food. While the detrimental effects of DON on human and animal reproductive systems have been well recognized, the underlying mechanism remains poorly understood. Ovarian granulosa cells (GCs), which surround oocytes, are crucial for regulating oocyte development, mainly through the secretion of hormones such as estrogen and progesterone. Using an in vitro model of murine GCs, we characterized the cytotoxic effects of DON and profiled genome-wide chromatin accessibility and transcriptomic alterations after DON exposure. Our results suggest that DON can induce decreased viability and growth, increased apoptosis rate, and disrupted hormone secretion. In total, 2533 differentially accessible loci and 2675 differentially expressed genes were identified that were associated with Hippo, Wnt, steroid biosynthesis, sulfur metabolism, and inflammation-related pathways. DON-induced genes usually have a concurrently increased occupancy of active histone modifications H3K4me3 and H3K27ac in their promoters. Integrative analyses identified 35 putative directly affected genes including Adrb2 and Fshr, which are key regulators of follicular growth, and revealed that regions with increased chromatin accessibility are enriched with the binding motifs for NR5A1 and NR5A2, which are important for GCs. Moreover, DON-induced inflammatory response is due to the activation of the NF-κB and MAPK signaling pathways. Overall, our results provide novel insights into the regulatory elements, genes, and key pathways underlying the response of ovarian GCs to DON cytotoxicity.Hairui FanZhanshi RenChao XuHaifei WangZhengchang WuZia ur RehmanShenglong WuMing-an SunWenbin BaoMDPI AGarticleovarian granulosa cellsmycotoxinchromatin accessibilitygene expressioncytotoxicityBiology (General)QH301-705.5ENCells, Vol 10, Iss 2818, p 2818 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ovarian granulosa cells mycotoxin chromatin accessibility gene expression cytotoxicity Biology (General) QH301-705.5
spellingShingle	ovarian granulosa cells mycotoxin chromatin accessibility gene expression cytotoxicity Biology (General) QH301-705.5 Hairui Fan Zhanshi Ren Chao Xu Haifei Wang Zhengchang Wu Zia ur Rehman Shenglong Wu Ming-an Sun Wenbin Bao Chromatin Accessibility and Transcriptomic Alterations in Murine Ovarian Granulosa Cells upon Deoxynivalenol Exposure
description	Deoxynivalenol (DON) is a common environmental toxin that is secreted by fusarium fungi that frequently contaminates feedstuff and food. While the detrimental effects of DON on human and animal reproductive systems have been well recognized, the underlying mechanism remains poorly understood. Ovarian granulosa cells (GCs), which surround oocytes, are crucial for regulating oocyte development, mainly through the secretion of hormones such as estrogen and progesterone. Using an in vitro model of murine GCs, we characterized the cytotoxic effects of DON and profiled genome-wide chromatin accessibility and transcriptomic alterations after DON exposure. Our results suggest that DON can induce decreased viability and growth, increased apoptosis rate, and disrupted hormone secretion. In total, 2533 differentially accessible loci and 2675 differentially expressed genes were identified that were associated with Hippo, Wnt, steroid biosynthesis, sulfur metabolism, and inflammation-related pathways. DON-induced genes usually have a concurrently increased occupancy of active histone modifications H3K4me3 and H3K27ac in their promoters. Integrative analyses identified 35 putative directly affected genes including Adrb2 and Fshr, which are key regulators of follicular growth, and revealed that regions with increased chromatin accessibility are enriched with the binding motifs for NR5A1 and NR5A2, which are important for GCs. Moreover, DON-induced inflammatory response is due to the activation of the NF-κB and MAPK signaling pathways. Overall, our results provide novel insights into the regulatory elements, genes, and key pathways underlying the response of ovarian GCs to DON cytotoxicity.
format	article
author	Hairui Fan Zhanshi Ren Chao Xu Haifei Wang Zhengchang Wu Zia ur Rehman Shenglong Wu Ming-an Sun Wenbin Bao
author_facet	Hairui Fan Zhanshi Ren Chao Xu Haifei Wang Zhengchang Wu Zia ur Rehman Shenglong Wu Ming-an Sun Wenbin Bao
author_sort	Hairui Fan
title	Chromatin Accessibility and Transcriptomic Alterations in Murine Ovarian Granulosa Cells upon Deoxynivalenol Exposure
title_short	Chromatin Accessibility and Transcriptomic Alterations in Murine Ovarian Granulosa Cells upon Deoxynivalenol Exposure
title_full	Chromatin Accessibility and Transcriptomic Alterations in Murine Ovarian Granulosa Cells upon Deoxynivalenol Exposure
title_fullStr	Chromatin Accessibility and Transcriptomic Alterations in Murine Ovarian Granulosa Cells upon Deoxynivalenol Exposure
title_full_unstemmed	Chromatin Accessibility and Transcriptomic Alterations in Murine Ovarian Granulosa Cells upon Deoxynivalenol Exposure
title_sort	chromatin accessibility and transcriptomic alterations in murine ovarian granulosa cells upon deoxynivalenol exposure
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/549d3028d7c4412681059a4d8b72b4bd
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Chromatin Accessibility and Transcriptomic Alterations in Murine Ovarian Granulosa Cells upon Deoxynivalenol Exposure

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