Exposure to Zinc Oxide Nanoparticles Increases Estradiol Levels and Induces an Antioxidant Response in Antral Ovarian Follicles In Vitro
The use of zinc oxide nanoparticles (ZnO NP) in consumer products is increasing, raising concern about their potential toxicity to human health. Nanoparticles have endocrine disrupting effects and can induce oxidative stress, leading to biomolecule oxidation and cell dysfunction. The ovary is one of...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/11/7/602 |
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| author | Ramsés Santacruz-Márquez Jodi A. Flaws Luz del Carmen Sánchez-Peña Isabel Hernández-Ochoa |
| author_facet | Ramsés Santacruz-Márquez Jodi A. Flaws Luz del Carmen Sánchez-Peña Isabel Hernández-Ochoa |
| author_sort | Ramsés Santacruz-Márquez |
| collection | DOAJ |
| description | The use of zinc oxide nanoparticles (ZnO NP) in consumer products is increasing, raising concern about their potential toxicity to human health. Nanoparticles have endocrine disrupting effects and can induce oxidative stress, leading to biomolecule oxidation and cell dysfunction. The ovary is one of the most important endocrine organs in female reproduction. Nanoparticles accumulate in the ovary, but it is unknown whether and how exposure to these materials disrupts antral follicle functions. Thus, this study tested the hypothesis that the in vitro exposure to ZnO NPs affects the steroidogenic pathway and induces oxidative stress in ovarian antral follicles. Antral follicles from CD-1 mice were cultured with ZnO NPs (5, 10, and 15 µg/mL) for 96 h. ZnO NP exposure did not affect apoptosis and cell cycle regulators at any of the tested concentrations. ZnO NP exposure at low levels (5 µg/mL) increased aromatase levels, leading to increased estradiol levels and decreased estrogen receptor alpha (<i>Esr1</i>) expression. ZnO NP exposure at 15 µg/mL induced an antioxidant response in the antral follicles as evidenced by changes in expression of antioxidant molecules (<i>Nrf2</i>, <i>Cat</i>, <i>Sod1</i>, <i>Gsr</i>, <i>Gpx</i>) and decreased levels of reactive oxygen species. Interestingly, ZnO NPs dissolve up to 50% in media and are internalized in cells as soon as 1 h after culture. In conclusion, ZnO NPs are internalized in antral follicles, leading to increased estrogen production and an antioxidant response. |
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| issn | 2305-6304 |
| language | English |
| last_indexed | 2024-03-11T00:36:24Z |
| publishDate | 2023-07-01 |
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| series | Toxics |
| spelling | doaj.art-a50c724c4c1c45f4aef9fba226f999642023-11-18T21:37:11ZengMDPI AGToxics2305-63042023-07-0111760210.3390/toxics11070602Exposure to Zinc Oxide Nanoparticles Increases Estradiol Levels and Induces an Antioxidant Response in Antral Ovarian Follicles In VitroRamsés Santacruz-Márquez0Jodi A. Flaws1Luz del Carmen Sánchez-Peña2Isabel Hernández-Ochoa3Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Departamento de Toxicología, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Mexico City 07360, MexicoDepartment of Comparative Biosciences, University of Illinois Urbana-Champaign, Urbana, IL 61802, USACentro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Departamento de Toxicología, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Mexico City 07360, MexicoCentro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Departamento de Toxicología, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Mexico City 07360, MexicoThe use of zinc oxide nanoparticles (ZnO NP) in consumer products is increasing, raising concern about their potential toxicity to human health. Nanoparticles have endocrine disrupting effects and can induce oxidative stress, leading to biomolecule oxidation and cell dysfunction. The ovary is one of the most important endocrine organs in female reproduction. Nanoparticles accumulate in the ovary, but it is unknown whether and how exposure to these materials disrupts antral follicle functions. Thus, this study tested the hypothesis that the in vitro exposure to ZnO NPs affects the steroidogenic pathway and induces oxidative stress in ovarian antral follicles. Antral follicles from CD-1 mice were cultured with ZnO NPs (5, 10, and 15 µg/mL) for 96 h. ZnO NP exposure did not affect apoptosis and cell cycle regulators at any of the tested concentrations. ZnO NP exposure at low levels (5 µg/mL) increased aromatase levels, leading to increased estradiol levels and decreased estrogen receptor alpha (<i>Esr1</i>) expression. ZnO NP exposure at 15 µg/mL induced an antioxidant response in the antral follicles as evidenced by changes in expression of antioxidant molecules (<i>Nrf2</i>, <i>Cat</i>, <i>Sod1</i>, <i>Gsr</i>, <i>Gpx</i>) and decreased levels of reactive oxygen species. Interestingly, ZnO NPs dissolve up to 50% in media and are internalized in cells as soon as 1 h after culture. In conclusion, ZnO NPs are internalized in antral follicles, leading to increased estrogen production and an antioxidant response.https://www.mdpi.com/2305-6304/11/7/602nanoparticlesZnO nanoparticlesantral folliclesovarytoxicityhormones |
| spellingShingle | Ramsés Santacruz-Márquez Jodi A. Flaws Luz del Carmen Sánchez-Peña Isabel Hernández-Ochoa Exposure to Zinc Oxide Nanoparticles Increases Estradiol Levels and Induces an Antioxidant Response in Antral Ovarian Follicles In Vitro Toxics nanoparticles ZnO nanoparticles antral follicles ovary toxicity hormones |
| title | Exposure to Zinc Oxide Nanoparticles Increases Estradiol Levels and Induces an Antioxidant Response in Antral Ovarian Follicles In Vitro |
| title_full | Exposure to Zinc Oxide Nanoparticles Increases Estradiol Levels and Induces an Antioxidant Response in Antral Ovarian Follicles In Vitro |
| title_fullStr | Exposure to Zinc Oxide Nanoparticles Increases Estradiol Levels and Induces an Antioxidant Response in Antral Ovarian Follicles In Vitro |
| title_full_unstemmed | Exposure to Zinc Oxide Nanoparticles Increases Estradiol Levels and Induces an Antioxidant Response in Antral Ovarian Follicles In Vitro |
| title_short | Exposure to Zinc Oxide Nanoparticles Increases Estradiol Levels and Induces an Antioxidant Response in Antral Ovarian Follicles In Vitro |
| title_sort | exposure to zinc oxide nanoparticles increases estradiol levels and induces an antioxidant response in antral ovarian follicles in vitro |
| topic | nanoparticles ZnO nanoparticles antral follicles ovary toxicity hormones |
| url | https://www.mdpi.com/2305-6304/11/7/602 |
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