Fecal microbiota transplantation alleviates female offspring’s ovarian inflammation in arsenic and fluoride co-exposed rats through the PI3K/ Akt /NF-κB pathway

Numerous studies have shown that exposure to arsenic (As) or fluoride(F) can damage the reproductive system, but limited evidence exists regarding the combined toxicity and pathogenesis of As and F co-exposure in female reproduction. Moreover, the role of gut microbiota in mediating such toxicity re...

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Main Authors: Yidi Li, Dongcai Yue, Yannan Zhao, Penghui Liu, Meng Li, Jinyao Chen, Xiaoting Yan, Linhua Fan, Guohua Song, Xiaolin Tian, Yi Lv, Qian Zhao, Yulan Qiu, Xiaoyan Yan
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S014765132500853X
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author Yidi Li
Dongcai Yue
Yannan Zhao
Penghui Liu
Meng Li
Jinyao Chen
Xiaoting Yan
Linhua Fan
Guohua Song
Xiaolin Tian
Yi Lv
Qian Zhao
Yulan Qiu
Xiaoyan Yan
author_facet Yidi Li
Dongcai Yue
Yannan Zhao
Penghui Liu
Meng Li
Jinyao Chen
Xiaoting Yan
Linhua Fan
Guohua Song
Xiaolin Tian
Yi Lv
Qian Zhao
Yulan Qiu
Xiaoyan Yan
author_sort Yidi Li
collection DOAJ
description Numerous studies have shown that exposure to arsenic (As) or fluoride(F) can damage the reproductive system, but limited evidence exists regarding the combined toxicity and pathogenesis of As and F co-exposure in female reproduction. Moreover, the role of gut microbiota in mediating such toxicity remains unclear. This study investigated the effects of As and F co-exposure on ovarian development and the potential protective role of fecal microbiota transplantation (FMT). We established an animal model of ovarian injury induced via co-exposure to NaAsO2 and NaF from birth to postnatal day 120(PND120) and introduced FMT from PND60. Co-exposure reduced serum levels of estradiol(E2) and luteinizing hormone (LH), along with morphological alterations in ovarian tissue. Meanwhile, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear transcription factor-κB (NF-κB) pathway, a known mediator of inflammation-related ovarian dysfunction, was significantly upregulated. Interestingly, with prolonged exposure, the inflammatory indicators (Akt, IL-1β, IL-6, TNF-α) on PND120 were significantly higher than those on PND60. Notably, FMT alleviated ovarian inflammation, potentially by improving colonic barrier function, thereby indirectly mitigating ovarian damage. Taken together, this study reveals that NaAsO2 and NaF co-exposure induces progressive ovarian inflammation via the PI3K/Akt/NF-κB pathway, and that FMT may offer protective effects. Our findings provide new insights into the environmental risks to female reproductive health.
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publishDate 2025-08-01
publisher Elsevier
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spelling doaj-art-8fc46c28daf34d63934bf76ccefc09ee2025-08-20T03:21:59ZengElsevierEcotoxicology and Environmental Safety0147-65132025-08-0130111850810.1016/j.ecoenv.2025.118508Fecal microbiota transplantation alleviates female offspring’s ovarian inflammation in arsenic and fluoride co-exposed rats through the PI3K/ Akt /NF-κB pathwayYidi Li0Dongcai Yue1Yannan Zhao2Penghui Liu3Meng Li4Jinyao Chen5Xiaoting Yan6Linhua Fan7Guohua Song8Xiaolin Tian9Yi Lv10Qian Zhao11Yulan Qiu12Xiaoyan Yan13School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaSchool of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaSchool of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Disease Prevention and Control Center of Handan City, Handan, Hebei 056000, ChinaSchool of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaSchool of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaSchool of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaFirst Clinical Medical College, Shanxi Medical University, Taiyuan 030001, ChinaLaboratory Animal Center, Shanxi Medical University, Taiyuan 030001, ChinaLaboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaSchool of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaSchool of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaSchool of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaSchool of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, ChinaSchool of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China; Corresponding author.Numerous studies have shown that exposure to arsenic (As) or fluoride(F) can damage the reproductive system, but limited evidence exists regarding the combined toxicity and pathogenesis of As and F co-exposure in female reproduction. Moreover, the role of gut microbiota in mediating such toxicity remains unclear. This study investigated the effects of As and F co-exposure on ovarian development and the potential protective role of fecal microbiota transplantation (FMT). We established an animal model of ovarian injury induced via co-exposure to NaAsO2 and NaF from birth to postnatal day 120(PND120) and introduced FMT from PND60. Co-exposure reduced serum levels of estradiol(E2) and luteinizing hormone (LH), along with morphological alterations in ovarian tissue. Meanwhile, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear transcription factor-κB (NF-κB) pathway, a known mediator of inflammation-related ovarian dysfunction, was significantly upregulated. Interestingly, with prolonged exposure, the inflammatory indicators (Akt, IL-1β, IL-6, TNF-α) on PND120 were significantly higher than those on PND60. Notably, FMT alleviated ovarian inflammation, potentially by improving colonic barrier function, thereby indirectly mitigating ovarian damage. Taken together, this study reveals that NaAsO2 and NaF co-exposure induces progressive ovarian inflammation via the PI3K/Akt/NF-κB pathway, and that FMT may offer protective effects. Our findings provide new insights into the environmental risks to female reproductive health.http://www.sciencedirect.com/science/article/pii/S014765132500853XArsenicFluorideOffspring ovaryInflammationFecal microbiota transplantation
spellingShingle Yidi Li
Dongcai Yue
Yannan Zhao
Penghui Liu
Meng Li
Jinyao Chen
Xiaoting Yan
Linhua Fan
Guohua Song
Xiaolin Tian
Yi Lv
Qian Zhao
Yulan Qiu
Xiaoyan Yan
Fecal microbiota transplantation alleviates female offspring’s ovarian inflammation in arsenic and fluoride co-exposed rats through the PI3K/ Akt /NF-κB pathway
Ecotoxicology and Environmental Safety
Arsenic
Fluoride
Offspring ovary
Inflammation
Fecal microbiota transplantation
title Fecal microbiota transplantation alleviates female offspring’s ovarian inflammation in arsenic and fluoride co-exposed rats through the PI3K/ Akt /NF-κB pathway
title_full Fecal microbiota transplantation alleviates female offspring’s ovarian inflammation in arsenic and fluoride co-exposed rats through the PI3K/ Akt /NF-κB pathway
title_fullStr Fecal microbiota transplantation alleviates female offspring’s ovarian inflammation in arsenic and fluoride co-exposed rats through the PI3K/ Akt /NF-κB pathway
title_full_unstemmed Fecal microbiota transplantation alleviates female offspring’s ovarian inflammation in arsenic and fluoride co-exposed rats through the PI3K/ Akt /NF-κB pathway
title_short Fecal microbiota transplantation alleviates female offspring’s ovarian inflammation in arsenic and fluoride co-exposed rats through the PI3K/ Akt /NF-κB pathway
title_sort fecal microbiota transplantation alleviates female offspring s ovarian inflammation in arsenic and fluoride co exposed rats through the pi3k akt nf κb pathway
topic Arsenic
Fluoride
Offspring ovary
Inflammation
Fecal microbiota transplantation
url http://www.sciencedirect.com/science/article/pii/S014765132500853X
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