Consecutive Low Doses of Streptozotocin Induce Polycystic Ovary Syndrome Features in Mice
Polycystic ovarian syndrome (PCOS) is a common reproductive endocrine disorder in reproductive-age women. Due to its various pathophysiological properties and clinical heterophenotypes, the mechanism of PCOS pathogenesis is still unclear. Several animal models have been used to study PCOS and allow...
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/3/1299 |
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| author | Youngjae Ryu Yong Jin Kim Yoon Young Kim Jungwoo Kim Sung Woo Kim Hoon Kim Seung Yup Ku |
| author_facet | Youngjae Ryu Yong Jin Kim Yoon Young Kim Jungwoo Kim Sung Woo Kim Hoon Kim Seung Yup Ku |
| author_sort | Youngjae Ryu |
| collection | DOAJ |
| description | Polycystic ovarian syndrome (PCOS) is a common reproductive endocrine disorder in reproductive-age women. Due to its various pathophysiological properties and clinical heterophenotypes, the mechanism of PCOS pathogenesis is still unclear. Several animal models have been used to study PCOS and allow the exploration of the specific mechanism underlying PCOS. We focused on streptozotocin (STZ) to develop a non-steroidal and non-diabetic PCOS model. We administered multiple STZ injections to female C57BL/6 mice (3–4 weeks old) at different concentrations: STZ-15 (15 mg/kg), STZ-30 (30 mg/kg), and STZ-60 (60 mg/kg) treatments. During the experimental period, we analyzed body weight, blood glucose levels, and estrous cycle pattern. Furthermore, five weeks after STZ administration, we examined hormone levels and the morphology of ovarian tissues. Mice in the STZ-15 group did not show differences in body weights, blood glucose level, insulin level, and insulin tolerance compared to wild-type and control groups whereas those in the STZ-60 group presented a typical diabetes phenotype. In the case of the STZ-30 group, only increased blood glucose level was observed. Total testosterone levels were significantly elevated in STZ-15 and STZ-30 groups. Luteinizing hormone (LH) and estradiol levels were not significantly changed in the STZ-treated groups. The number of ovarian antral follicles and atretic follicles significantly increased in the ovary of mice in the STZ-15 and STZ-30 groups. All STZ-treated groups manifested irregular estrus cycles. However, the patterns of estrous cycles were different between mice treated with different STZ concentrations. We found that PI3K-AKT and IRS-1 signaling in the ovary was enhanced by low doses of STZ treatment. Taken together, our finding indicates that multiple injections of STZ at low doses induce PCOS features in mice without induction of diabetes features. |
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| language | English |
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| spelling | doaj.art-e7a158f1e6c747728724ca21c7247d6e2023-12-03T15:04:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01223129910.3390/ijms22031299Consecutive Low Doses of Streptozotocin Induce Polycystic Ovary Syndrome Features in MiceYoungjae Ryu0Yong Jin Kim1Yoon Young Kim2Jungwoo Kim3Sung Woo Kim4Hoon Kim5Seung Yup Ku6Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, KoreaDepartment of Obstetrics and Gynecology, Korea University College of Medicine, Seoul 02841, KoreaBiomedical Research Institute, Seoul National University Hospital, Seoul 03080, KoreaInstitute of Reproductive Medicine and Population, Medical Research Center, Seoul National University College of Medicine, Seoul 03080, KoreaDepartment of Obstetrics and Gynecology, Seoul National University Hospital, Seoul 03080, KoreaDepartment of Obstetrics and Gynecology, Seoul National University Hospital, Seoul 03080, KoreaInstitute of Reproductive Medicine and Population, Medical Research Center, Seoul National University College of Medicine, Seoul 03080, KoreaPolycystic ovarian syndrome (PCOS) is a common reproductive endocrine disorder in reproductive-age women. Due to its various pathophysiological properties and clinical heterophenotypes, the mechanism of PCOS pathogenesis is still unclear. Several animal models have been used to study PCOS and allow the exploration of the specific mechanism underlying PCOS. We focused on streptozotocin (STZ) to develop a non-steroidal and non-diabetic PCOS model. We administered multiple STZ injections to female C57BL/6 mice (3–4 weeks old) at different concentrations: STZ-15 (15 mg/kg), STZ-30 (30 mg/kg), and STZ-60 (60 mg/kg) treatments. During the experimental period, we analyzed body weight, blood glucose levels, and estrous cycle pattern. Furthermore, five weeks after STZ administration, we examined hormone levels and the morphology of ovarian tissues. Mice in the STZ-15 group did not show differences in body weights, blood glucose level, insulin level, and insulin tolerance compared to wild-type and control groups whereas those in the STZ-60 group presented a typical diabetes phenotype. In the case of the STZ-30 group, only increased blood glucose level was observed. Total testosterone levels were significantly elevated in STZ-15 and STZ-30 groups. Luteinizing hormone (LH) and estradiol levels were not significantly changed in the STZ-treated groups. The number of ovarian antral follicles and atretic follicles significantly increased in the ovary of mice in the STZ-15 and STZ-30 groups. All STZ-treated groups manifested irregular estrus cycles. However, the patterns of estrous cycles were different between mice treated with different STZ concentrations. We found that PI3K-AKT and IRS-1 signaling in the ovary was enhanced by low doses of STZ treatment. Taken together, our finding indicates that multiple injections of STZ at low doses induce PCOS features in mice without induction of diabetes features.https://www.mdpi.com/1422-0067/22/3/1299polycystic ovary syndromestreptozotocinanimal modelsovarytestosterone |
| spellingShingle | Youngjae Ryu Yong Jin Kim Yoon Young Kim Jungwoo Kim Sung Woo Kim Hoon Kim Seung Yup Ku Consecutive Low Doses of Streptozotocin Induce Polycystic Ovary Syndrome Features in Mice International Journal of Molecular Sciences polycystic ovary syndrome streptozotocin animal models ovary testosterone |
| title | Consecutive Low Doses of Streptozotocin Induce Polycystic Ovary Syndrome Features in Mice |
| title_full | Consecutive Low Doses of Streptozotocin Induce Polycystic Ovary Syndrome Features in Mice |
| title_fullStr | Consecutive Low Doses of Streptozotocin Induce Polycystic Ovary Syndrome Features in Mice |
| title_full_unstemmed | Consecutive Low Doses of Streptozotocin Induce Polycystic Ovary Syndrome Features in Mice |
| title_short | Consecutive Low Doses of Streptozotocin Induce Polycystic Ovary Syndrome Features in Mice |
| title_sort | consecutive low doses of streptozotocin induce polycystic ovary syndrome features in mice |
| topic | polycystic ovary syndrome streptozotocin animal models ovary testosterone |
| url | https://www.mdpi.com/1422-0067/22/3/1299 |
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