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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Elsevier
2025-09-01
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| 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. |
| format | Article |
| id | doaj-art-2a93aaed164b42f49279de1d43e7d302 |
| institution | DOAJ |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| 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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