Linoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the ER-FOXO1-ROS-NFκB pathway

Abstract Polycystic ovary syndrome (PCOS) is a complex reproductive endocrinological disorder influenced by a combination of genetic and environmental factors. Linoleic acid (LA) is a widely consumed ω-6 polyunsaturated fatty acid, accounting for approximately 80% of daily fatty acid intake. Buildin...

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Main Authors: Wenying Zhang, Fuju Wu
Format: Article
Language:English
Published: Nature Portfolio 2024-03-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-024-56970-x
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author Wenying Zhang
Fuju Wu
author_facet Wenying Zhang
Fuju Wu
author_sort Wenying Zhang
collection DOAJ
description Abstract Polycystic ovary syndrome (PCOS) is a complex reproductive endocrinological disorder influenced by a combination of genetic and environmental factors. Linoleic acid (LA) is a widely consumed ω-6 polyunsaturated fatty acid, accounting for approximately 80% of daily fatty acid intake. Building upon the prior investigations of our team, which established a connection between LA levels in the follicular fluid and PCOS, this study deeply examined the specific impact of LA using a granulosa cell line. Our findings revealed that LA exerts its influence on granulosa cells (GCs) by binding to the estrogen receptor (ER). Activated ER triggers the transcription of the FOXO1 gene. Reactive oxygen species (ROS)-related oxidative stress (OS) and inflammation occur downstream of LA-induced FOXO1 activation. Increased OS and inflammation ultimately culminate in GC apoptosis. In summary, LA modulates the apoptosis and inflammation phenotypes of GCs through the ER-FOXO1-ROS-NF-κB pathway. Our study provides additional experimental evidence to comprehend the pathophysiology of PCOS and provides novel insights into the dietary management of individuals with PCOS.
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spelling doaj.art-75fc50d5d5244a839f3f0f9a3f5d5c3e2024-03-17T12:21:45ZengNature PortfolioScientific Reports2045-23222024-03-0114111310.1038/s41598-024-56970-xLinoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the ER-FOXO1-ROS-NFκB pathwayWenying Zhang0Fuju Wu1Department of Obstetrics and Gynecology, The Second Hospital of Jilin UniversityDepartment of Obstetrics and Gynecology, The Second Hospital of Jilin UniversityAbstract Polycystic ovary syndrome (PCOS) is a complex reproductive endocrinological disorder influenced by a combination of genetic and environmental factors. Linoleic acid (LA) is a widely consumed ω-6 polyunsaturated fatty acid, accounting for approximately 80% of daily fatty acid intake. Building upon the prior investigations of our team, which established a connection between LA levels in the follicular fluid and PCOS, this study deeply examined the specific impact of LA using a granulosa cell line. Our findings revealed that LA exerts its influence on granulosa cells (GCs) by binding to the estrogen receptor (ER). Activated ER triggers the transcription of the FOXO1 gene. Reactive oxygen species (ROS)-related oxidative stress (OS) and inflammation occur downstream of LA-induced FOXO1 activation. Increased OS and inflammation ultimately culminate in GC apoptosis. In summary, LA modulates the apoptosis and inflammation phenotypes of GCs through the ER-FOXO1-ROS-NF-κB pathway. Our study provides additional experimental evidence to comprehend the pathophysiology of PCOS and provides novel insights into the dietary management of individuals with PCOS.https://doi.org/10.1038/s41598-024-56970-xLinoleic acidGranulosa cellDietary fatty acidsPolycystic ovary syndromeApoptosisEstrogen receptor
spellingShingle Wenying Zhang
Fuju Wu
Linoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the ER-FOXO1-ROS-NFκB pathway
Scientific Reports
Linoleic acid
Granulosa cell
Dietary fatty acids
Polycystic ovary syndrome
Apoptosis
Estrogen receptor
title Linoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the ER-FOXO1-ROS-NFκB pathway
title_full Linoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the ER-FOXO1-ROS-NFκB pathway
title_fullStr Linoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the ER-FOXO1-ROS-NFκB pathway
title_full_unstemmed Linoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the ER-FOXO1-ROS-NFκB pathway
title_short Linoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the ER-FOXO1-ROS-NFκB pathway
title_sort linoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the er foxo1 ros nfκb pathway
topic Linoleic acid
Granulosa cell
Dietary fatty acids
Polycystic ovary syndrome
Apoptosis
Estrogen receptor
url https://doi.org/10.1038/s41598-024-56970-x
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