The impact of prenatal amoxicillin exposure at different doses, stages, and courses on offspring ovarian development
Abstract Background Amoxicillin, a commonly used broad-spectrum penicillin antibiotic in pregnancy, has sparked controversy regarding its impact on fetal growth and development. There remains a lack of systematic research on the specific influence of prenatal amoxicillin exposure (PAmE) on the ovari...
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BMC
2025-07-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-025-01322-2 |
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| author | Jing Huang Yating Li Ming Zhang Tiancheng Wu Yuanzhen Zhang Hui Wang |
| author_facet | Jing Huang Yating Li Ming Zhang Tiancheng Wu Yuanzhen Zhang Hui Wang |
| author_sort | Jing Huang |
| collection | DOAJ |
| description | Abstract Background Amoxicillin, a commonly used broad-spectrum penicillin antibiotic in pregnancy, has sparked controversy regarding its impact on fetal growth and development. There remains a lack of systematic research on the specific influence of prenatal amoxicillin exposure (PAmE) on the ovarian development of the offspring, as well as the precise " toxicity windows “. Methods We established PAmE mouse models at different stages [(gestational day, GD) 10–12, GD13-15 or GD16-18], doses (75, 150 or 300 mg/kg·d), and courses (single/multiple courses). On GD18, fetal serum and ovaries were collected to assess changes in serum estradiol levels and evaluate ovarian morphology, pregranulosa cell function, and oocyte-related parameters. Results PAmE led to pathological damage in fetal mouse ovaries, characterized by disrupted germ cell cysts and reduced the number of germ cells. Cell proliferation was enhanced while apoptosis was reduced. Moreover, PAmE upregulated the expression of pregranulosa cell steroid synthesis-related genes (e.g., Sf1, Star, P450scc) in the fetal ovaries, particularly in the high-dose groups at all gestational stages. The expression of the oocyte marker gene Figlα increased in all PAmE groups, while follicle development-related genes (Nobox and Bmp15) were downregulated, particularly during early to mid-pregnancy and in the single-course exposure groups. Further investigation revealed that PAmE enhanced IGF1 expression in fetal ovaries and inhibited the Pten-Akt-Foxo3a signaling pathway. Conclusions Amoxicillin exhibits ovarian developmental toxicity, influencing fetal ovarian cell proliferation, apoptosis, pregranulosa cell estrogen synthesis, oocyte numbers, and follicle assembly. This study provides evidence guiding the rational use of amoxicillin in pregnancy and assessing potential ovarian development risks. Graphical Abstract |
| format | Article |
| id | doaj-art-e6818dc7aaf945fb8b8c12c87cf85ce4 |
| institution | Kabale University |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-e6818dc7aaf945fb8b8c12c87cf85ce42025-08-20T04:02:57ZengBMCMolecular Medicine1528-36582025-07-0131111310.1186/s10020-025-01322-2The impact of prenatal amoxicillin exposure at different doses, stages, and courses on offspring ovarian developmentJing Huang0Yating Li1Ming Zhang2Tiancheng Wu3Yuanzhen Zhang4Hui Wang5Department of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan UniversityDepartment of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan UniversityHubei Provincial Key Laboratory of Developmentally Originated DiseaseDepartment of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan UniversityDepartment of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan UniversityDepartment of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan UniversityAbstract Background Amoxicillin, a commonly used broad-spectrum penicillin antibiotic in pregnancy, has sparked controversy regarding its impact on fetal growth and development. There remains a lack of systematic research on the specific influence of prenatal amoxicillin exposure (PAmE) on the ovarian development of the offspring, as well as the precise " toxicity windows “. Methods We established PAmE mouse models at different stages [(gestational day, GD) 10–12, GD13-15 or GD16-18], doses (75, 150 or 300 mg/kg·d), and courses (single/multiple courses). On GD18, fetal serum and ovaries were collected to assess changes in serum estradiol levels and evaluate ovarian morphology, pregranulosa cell function, and oocyte-related parameters. Results PAmE led to pathological damage in fetal mouse ovaries, characterized by disrupted germ cell cysts and reduced the number of germ cells. Cell proliferation was enhanced while apoptosis was reduced. Moreover, PAmE upregulated the expression of pregranulosa cell steroid synthesis-related genes (e.g., Sf1, Star, P450scc) in the fetal ovaries, particularly in the high-dose groups at all gestational stages. The expression of the oocyte marker gene Figlα increased in all PAmE groups, while follicle development-related genes (Nobox and Bmp15) were downregulated, particularly during early to mid-pregnancy and in the single-course exposure groups. Further investigation revealed that PAmE enhanced IGF1 expression in fetal ovaries and inhibited the Pten-Akt-Foxo3a signaling pathway. Conclusions Amoxicillin exhibits ovarian developmental toxicity, influencing fetal ovarian cell proliferation, apoptosis, pregranulosa cell estrogen synthesis, oocyte numbers, and follicle assembly. This study provides evidence guiding the rational use of amoxicillin in pregnancy and assessing potential ovarian development risks. Graphical Abstracthttps://doi.org/10.1186/s10020-025-01322-2Prenatal amoxicillin exposureOvarian developmental toxicityPregranulosa cellsOocytesMedication safety |
| spellingShingle | Jing Huang Yating Li Ming Zhang Tiancheng Wu Yuanzhen Zhang Hui Wang The impact of prenatal amoxicillin exposure at different doses, stages, and courses on offspring ovarian development Molecular Medicine Prenatal amoxicillin exposure Ovarian developmental toxicity Pregranulosa cells Oocytes Medication safety |
| title | The impact of prenatal amoxicillin exposure at different doses, stages, and courses on offspring ovarian development |
| title_full | The impact of prenatal amoxicillin exposure at different doses, stages, and courses on offspring ovarian development |
| title_fullStr | The impact of prenatal amoxicillin exposure at different doses, stages, and courses on offspring ovarian development |
| title_full_unstemmed | The impact of prenatal amoxicillin exposure at different doses, stages, and courses on offspring ovarian development |
| title_short | The impact of prenatal amoxicillin exposure at different doses, stages, and courses on offspring ovarian development |
| title_sort | impact of prenatal amoxicillin exposure at different doses stages and courses on offspring ovarian development |
| topic | Prenatal amoxicillin exposure Ovarian developmental toxicity Pregranulosa cells Oocytes Medication safety |
| url | https://doi.org/10.1186/s10020-025-01322-2 |
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