Implications of a combined perinatal exposure to BPA and BP-3 for offspring folliculogenesis and ovarian function in mice

Endocrine disrupting chemicals (EDCs), like bisphenol A (BPA) and benzophenone-3 (BP-3), can interfere with hormone systems, posing risks to fertility and reproduction. Exposure to EDCs is unavoidable making it a relevant environmental health topic, however the impact of real-life EDC mixtures is la...

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Main Authors: Elisabeth Krieger, Florence Fischer, Julia Howanski, Marita Wagner, Federica Romanelli, Beate Fink, Mario Bauer, Anne Schumacher, Tobias Kretschmer, Ana C. Zenclussen
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325010954
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author Elisabeth Krieger
Florence Fischer
Julia Howanski
Marita Wagner
Federica Romanelli
Beate Fink
Mario Bauer
Anne Schumacher
Tobias Kretschmer
Ana C. Zenclussen
author_facet Elisabeth Krieger
Florence Fischer
Julia Howanski
Marita Wagner
Federica Romanelli
Beate Fink
Mario Bauer
Anne Schumacher
Tobias Kretschmer
Ana C. Zenclussen
author_sort Elisabeth Krieger
collection DOAJ
description Endocrine disrupting chemicals (EDCs), like bisphenol A (BPA) and benzophenone-3 (BP-3), can interfere with hormone systems, posing risks to fertility and reproduction. Exposure to EDCs is unavoidable making it a relevant environmental health topic, however the impact of real-life EDC mixtures is largely unknown. This study explored the effects of a combined BPA and BP-3 exposure at tolerable intake levels for humans during pregnancy and early life on ovarian development and function in an established mouse model. Mice were daily exposed to concentrations of 4 µg/kg BPA orally, 50 mg/kg BP-3 dermally, and the combination of BPA+BP-3 through gestation and lactation, a susceptible developmental period. Female offspring of BPA and BP-3 exposed mice exhibited increased birth weight and elevated bodyweight by postnatal day 7. By day 30, after hormonal stimulation to induce ovulation, exposed offspring showed disrupted ovarian follicle maturation and altered ovarian response to stimulation with exogenous gonadotropins. Moreover, the number of NK cells rose in the ovaries, and genes linked to hormone signaling, hormone synthesis, and ovarian tissue remodeling were altered relative to unexposed controls. These findings suggest that early life exposure to BPA and BP-3 at environmentally relevant doses impairs ovarian development and function in mice indicating that immune cells and hormonal signaling in the ovaries are targets of endocrine disruptors at relevant concentrations. Such endocrine disruption may be compromising fertility and reproductive health in later life. Our research underscores the importance of investigating the impact of combined EDC exposure on the reproductive system.
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spelling doaj-art-2a93aaed164b42f49279de1d43e7d3022025-08-20T03:05:34ZengElsevierEcotoxicology and Environmental Safety0147-65132025-09-0130211875010.1016/j.ecoenv.2025.118750Implications of a combined perinatal exposure to BPA and BP-3 for offspring folliculogenesis and ovarian function in miceElisabeth Krieger0Florence Fischer1Julia Howanski2Marita Wagner3Federica Romanelli4Beate Fink5Mario Bauer6Anne Schumacher7Tobias Kretschmer8Ana C. Zenclussen9Department of Environmental Immunology, Helmholtz-Center for Environmental Research – UFZ, Permoserstrasse 15, Leipzig 04318, Germany; Perinatal Immunology, Saxonian Incubator for Clinical Translation (SIKT), Medical Faculty, Leipzig University, Philipp-Rosenthal-Strasse 55, Leipzig 04103, GermanyDepartment of Environmental Immunology, Helmholtz-Center for Environmental Research – UFZ, Permoserstrasse 15, Leipzig 04318, Germany; Perinatal Immunology, Saxonian Incubator for Clinical Translation (SIKT), Medical Faculty, Leipzig University, Philipp-Rosenthal-Strasse 55, Leipzig 04103, Germany; Institute for Clinical Immunology, Leipzig University, Johannisallee 30, Leipzig 04103, GermanyDepartment of Environmental Immunology, Helmholtz-Center for Environmental Research – UFZ, Permoserstrasse 15, Leipzig 04318, Germany; Perinatal Immunology, Saxonian Incubator for Clinical Translation (SIKT), Medical Faculty, Leipzig University, Philipp-Rosenthal-Strasse 55, Leipzig 04103, GermanyDepartment of Environmental Immunology, Helmholtz-Center for Environmental Research – UFZ, Permoserstrasse 15, Leipzig 04318, GermanyDepartment of Environmental Immunology, Helmholtz-Center for Environmental Research – UFZ, Permoserstrasse 15, Leipzig 04318, Germany; Perinatal Immunology, Saxonian Incubator for Clinical Translation (SIKT), Medical Faculty, Leipzig University, Philipp-Rosenthal-Strasse 55, Leipzig 04103, GermanyDepartment of Environmental Immunology, Helmholtz-Center for Environmental Research – UFZ, Permoserstrasse 15, Leipzig 04318, GermanyDepartment of Environmental Immunology, Helmholtz-Center for Environmental Research – UFZ, Permoserstrasse 15, Leipzig 04318, GermanyDepartment of Environmental Immunology, Helmholtz-Center for Environmental Research – UFZ, Permoserstrasse 15, Leipzig 04318, Germany; Perinatal Immunology, Saxonian Incubator for Clinical Translation (SIKT), Medical Faculty, Leipzig University, Philipp-Rosenthal-Strasse 55, Leipzig 04103, Germany; Leipzig Reproductive Health Research Center (LE-REP), Leipzig University, Liebigstrasse 20a, Leipzig 04103, GermanyDepartment of Environmental Immunology, Helmholtz-Center for Environmental Research – UFZ, Permoserstrasse 15, Leipzig 04318, Germany; Perinatal Immunology, Saxonian Incubator for Clinical Translation (SIKT), Medical Faculty, Leipzig University, Philipp-Rosenthal-Strasse 55, Leipzig 04103, Germany; Leipzig Reproductive Health Research Center (LE-REP), Leipzig University, Liebigstrasse 20a, Leipzig 04103, Germany; Corresponding author at: Department of Environmental Immunology, Helmholtz-Center for Environmental Research – UFZ, Permoserstrasse 15, Leipzig 04318, Germany.Department of Environmental Immunology, Helmholtz-Center for Environmental Research – UFZ, Permoserstrasse 15, Leipzig 04318, Germany; Perinatal Immunology, Saxonian Incubator for Clinical Translation (SIKT), Medical Faculty, Leipzig University, Philipp-Rosenthal-Strasse 55, Leipzig 04103, Germany; Leipzig Reproductive Health Research Center (LE-REP), Leipzig University, Liebigstrasse 20a, Leipzig 04103, Germany; German Center for Child and Adolescent Health (DZKJ), partner site Leipzig/Dresden, Germany; Corresponding author at: Department of Environmental Immunology, Helmholtz-Center for Environmental Research – UFZ, Permoserstrasse 15, Leipzig 04318, Germany.Endocrine disrupting chemicals (EDCs), like bisphenol A (BPA) and benzophenone-3 (BP-3), can interfere with hormone systems, posing risks to fertility and reproduction. Exposure to EDCs is unavoidable making it a relevant environmental health topic, however the impact of real-life EDC mixtures is largely unknown. This study explored the effects of a combined BPA and BP-3 exposure at tolerable intake levels for humans during pregnancy and early life on ovarian development and function in an established mouse model. Mice were daily exposed to concentrations of 4 µg/kg BPA orally, 50 mg/kg BP-3 dermally, and the combination of BPA+BP-3 through gestation and lactation, a susceptible developmental period. Female offspring of BPA and BP-3 exposed mice exhibited increased birth weight and elevated bodyweight by postnatal day 7. By day 30, after hormonal stimulation to induce ovulation, exposed offspring showed disrupted ovarian follicle maturation and altered ovarian response to stimulation with exogenous gonadotropins. Moreover, the number of NK cells rose in the ovaries, and genes linked to hormone signaling, hormone synthesis, and ovarian tissue remodeling were altered relative to unexposed controls. These findings suggest that early life exposure to BPA and BP-3 at environmentally relevant doses impairs ovarian development and function in mice indicating that immune cells and hormonal signaling in the ovaries are targets of endocrine disruptors at relevant concentrations. Such endocrine disruption may be compromising fertility and reproductive health in later life. Our research underscores the importance of investigating the impact of combined EDC exposure on the reproductive system.http://www.sciencedirect.com/science/article/pii/S0147651325010954Endocrine disrupting chemicalsBisphenol ABenzophenone-3FolliculogenesisOvarian functionFertility
spellingShingle Elisabeth Krieger
Florence Fischer
Julia Howanski
Marita Wagner
Federica Romanelli
Beate Fink
Mario Bauer
Anne Schumacher
Tobias Kretschmer
Ana C. Zenclussen
Implications of a combined perinatal exposure to BPA and BP-3 for offspring folliculogenesis and ovarian function in mice
Ecotoxicology and Environmental Safety
Endocrine disrupting chemicals
Bisphenol A
Benzophenone-3
Folliculogenesis
Ovarian function
Fertility
title Implications of a combined perinatal exposure to BPA and BP-3 for offspring folliculogenesis and ovarian function in mice
title_full Implications of a combined perinatal exposure to BPA and BP-3 for offspring folliculogenesis and ovarian function in mice
title_fullStr Implications of a combined perinatal exposure to BPA and BP-3 for offspring folliculogenesis and ovarian function in mice
title_full_unstemmed Implications of a combined perinatal exposure to BPA and BP-3 for offspring folliculogenesis and ovarian function in mice
title_short Implications of a combined perinatal exposure to BPA and BP-3 for offspring folliculogenesis and ovarian function in mice
title_sort implications of a combined perinatal exposure to bpa and bp 3 for offspring folliculogenesis and ovarian function in mice
topic Endocrine disrupting chemicals
Bisphenol A
Benzophenone-3
Folliculogenesis
Ovarian function
Fertility
url http://www.sciencedirect.com/science/article/pii/S0147651325010954
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