Prenatal Perfluorooctanoic Acid (PFOA) exposure causes reproductive toxicity by disrupting the formation of transzonal projections (TZPs) and down-regulating Wnt4/β-catenin signaling pathway in progeny

Perfluorooctanoic acid (PFOA) has been recognized as a novel persistent organic pollutant, playing a significant role in global environmental contamination. Recent evidence indicates that exposure to PFOA detrimentally affects reproductive function, notably through a progressive decline in ovarian f...

Full description

Saved in:
Bibliographic Details
Main Authors: Hua Du, Lishuang Song, Min Zhao, Xiaorong Zhao, Ren Mu, Shengtao Gao, Bin Zhang, Jiapeng Wang
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Ecotoxicology and Environmental Safety
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325001526
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850230023749894144
author Hua Du
Lishuang Song
Min Zhao
Xiaorong Zhao
Ren Mu
Shengtao Gao
Bin Zhang
Jiapeng Wang
author_facet Hua Du
Lishuang Song
Min Zhao
Xiaorong Zhao
Ren Mu
Shengtao Gao
Bin Zhang
Jiapeng Wang
author_sort Hua Du
collection DOAJ
description Perfluorooctanoic acid (PFOA) has been recognized as a novel persistent organic pollutant, playing a significant role in global environmental contamination. Recent evidence indicates that exposure to PFOA detrimentally affects reproductive function, notably through a progressive decline in ovarian function. However, there is a notable lack of research specifically examining its impact on the reproductive potential of female offspring. In this study, we report that prenatal exposure to PFOA impairs the competence of maturing oocytes and reduces the yield of oocytes in the progeny. Mechanistically, prenatal exposure to PFOA leads to a reduced expression of Wnt4, which subsequently impairs the integrity of the ovarian follicle basement membrane and decreases the expression of proteins related to adherent junctions in granulosa cells. This cascade of events results in a compromised reduction of transzonal projections (TZPs) within ovarian follicles, ultimately leading to mitochondrial dysfunction and diminished ATP synthesis in oocytes. This study offers comprehensive insights into the underlying mechanisms of PFOA-induced reproductive toxicity and furnishes scientific evidence to support initiatives focused on preventing and mitigating reproductive harm associated with perfluorinated compounds.
format Article
id doaj-art-c97ab2bbbb494f7f8ef306a561a55540
institution OA Journals
issn 0147-6513
language English
publishDate 2025-02-01
publisher Elsevier
record_format Article
series Ecotoxicology and Environmental Safety
spelling doaj-art-c97ab2bbbb494f7f8ef306a561a555402025-08-20T02:04:00ZengElsevierEcotoxicology and Environmental Safety0147-65132025-02-0129111781610.1016/j.ecoenv.2025.117816Prenatal Perfluorooctanoic Acid (PFOA) exposure causes reproductive toxicity by disrupting the formation of transzonal projections (TZPs) and down-regulating Wnt4/β-catenin signaling pathway in progenyHua Du0Lishuang Song1Min Zhao2Xiaorong Zhao3Ren Mu4Shengtao Gao5Bin Zhang6Jiapeng Wang7Department of Pathology, Basic Medical College/Affifiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia, ChinaCollege of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia, ChinaCollege of Life Sciences and Technology, Inner Mongolia Normal University, Hohhot, Inner Mongolia, ChinaCollege of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia, ChinaCollege of Life Sciences and Technology, Inner Mongolia Normal University, Hohhot, Inner Mongolia, ChinaCollege of Life Sciences and Technology, Inner Mongolia Normal University, Hohhot, Inner Mongolia, ChinaCollege of Life Sciences and Technology, Inner Mongolia Normal University, Hohhot, Inner Mongolia, China; Corresponding authors.College of Life Sciences and Technology, Inner Mongolia Normal University, Hohhot, Inner Mongolia, China; Corresponding authors.Perfluorooctanoic acid (PFOA) has been recognized as a novel persistent organic pollutant, playing a significant role in global environmental contamination. Recent evidence indicates that exposure to PFOA detrimentally affects reproductive function, notably through a progressive decline in ovarian function. However, there is a notable lack of research specifically examining its impact on the reproductive potential of female offspring. In this study, we report that prenatal exposure to PFOA impairs the competence of maturing oocytes and reduces the yield of oocytes in the progeny. Mechanistically, prenatal exposure to PFOA leads to a reduced expression of Wnt4, which subsequently impairs the integrity of the ovarian follicle basement membrane and decreases the expression of proteins related to adherent junctions in granulosa cells. This cascade of events results in a compromised reduction of transzonal projections (TZPs) within ovarian follicles, ultimately leading to mitochondrial dysfunction and diminished ATP synthesis in oocytes. This study offers comprehensive insights into the underlying mechanisms of PFOA-induced reproductive toxicity and furnishes scientific evidence to support initiatives focused on preventing and mitigating reproductive harm associated with perfluorinated compounds.http://www.sciencedirect.com/science/article/pii/S0147651325001526Perfluorooctanoic acidTranszonal projectionsβ-cateninN-cadherinWnt4
spellingShingle Hua Du
Lishuang Song
Min Zhao
Xiaorong Zhao
Ren Mu
Shengtao Gao
Bin Zhang
Jiapeng Wang
Prenatal Perfluorooctanoic Acid (PFOA) exposure causes reproductive toxicity by disrupting the formation of transzonal projections (TZPs) and down-regulating Wnt4/β-catenin signaling pathway in progeny
Ecotoxicology and Environmental Safety
Perfluorooctanoic acid
Transzonal projections
β-catenin
N-cadherin
Wnt4
title Prenatal Perfluorooctanoic Acid (PFOA) exposure causes reproductive toxicity by disrupting the formation of transzonal projections (TZPs) and down-regulating Wnt4/β-catenin signaling pathway in progeny
title_full Prenatal Perfluorooctanoic Acid (PFOA) exposure causes reproductive toxicity by disrupting the formation of transzonal projections (TZPs) and down-regulating Wnt4/β-catenin signaling pathway in progeny
title_fullStr Prenatal Perfluorooctanoic Acid (PFOA) exposure causes reproductive toxicity by disrupting the formation of transzonal projections (TZPs) and down-regulating Wnt4/β-catenin signaling pathway in progeny
title_full_unstemmed Prenatal Perfluorooctanoic Acid (PFOA) exposure causes reproductive toxicity by disrupting the formation of transzonal projections (TZPs) and down-regulating Wnt4/β-catenin signaling pathway in progeny
title_short Prenatal Perfluorooctanoic Acid (PFOA) exposure causes reproductive toxicity by disrupting the formation of transzonal projections (TZPs) and down-regulating Wnt4/β-catenin signaling pathway in progeny
title_sort prenatal perfluorooctanoic acid pfoa exposure causes reproductive toxicity by disrupting the formation of transzonal projections tzps and down regulating wnt4 β catenin signaling pathway in progeny
topic Perfluorooctanoic acid
Transzonal projections
β-catenin
N-cadherin
Wnt4
url http://www.sciencedirect.com/science/article/pii/S0147651325001526
work_keys_str_mv AT huadu prenatalperfluorooctanoicacidpfoaexposurecausesreproductivetoxicitybydisruptingtheformationoftranszonalprojectionstzpsanddownregulatingwnt4bcateninsignalingpathwayinprogeny
AT lishuangsong prenatalperfluorooctanoicacidpfoaexposurecausesreproductivetoxicitybydisruptingtheformationoftranszonalprojectionstzpsanddownregulatingwnt4bcateninsignalingpathwayinprogeny
AT minzhao prenatalperfluorooctanoicacidpfoaexposurecausesreproductivetoxicitybydisruptingtheformationoftranszonalprojectionstzpsanddownregulatingwnt4bcateninsignalingpathwayinprogeny
AT xiaorongzhao prenatalperfluorooctanoicacidpfoaexposurecausesreproductivetoxicitybydisruptingtheformationoftranszonalprojectionstzpsanddownregulatingwnt4bcateninsignalingpathwayinprogeny
AT renmu prenatalperfluorooctanoicacidpfoaexposurecausesreproductivetoxicitybydisruptingtheformationoftranszonalprojectionstzpsanddownregulatingwnt4bcateninsignalingpathwayinprogeny
AT shengtaogao prenatalperfluorooctanoicacidpfoaexposurecausesreproductivetoxicitybydisruptingtheformationoftranszonalprojectionstzpsanddownregulatingwnt4bcateninsignalingpathwayinprogeny
AT binzhang prenatalperfluorooctanoicacidpfoaexposurecausesreproductivetoxicitybydisruptingtheformationoftranszonalprojectionstzpsanddownregulatingwnt4bcateninsignalingpathwayinprogeny
AT jiapengwang prenatalperfluorooctanoicacidpfoaexposurecausesreproductivetoxicitybydisruptingtheformationoftranszonalprojectionstzpsanddownregulatingwnt4bcateninsignalingpathwayinprogeny