Cargando…
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...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865447/ https://www.ncbi.nlm.nih.gov/pubmed/33525535 http://dx.doi.org/10.3390/ijms22031299 |
_version_ | 1783647848290582528 |
---|---|
author | Ryu, Youngjae Kim, Yong Jin Kim, Yoon Young Kim, Jungwoo Kim, Sung Woo Kim, Hoon Ku, Seung Yup |
author_facet | Ryu, Youngjae Kim, Yong Jin Kim, Yoon Young Kim, Jungwoo Kim, Sung Woo Kim, Hoon Ku, Seung Yup |
author_sort | Ryu, Youngjae |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-7865447 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78654472021-02-07 Consecutive Low Doses of Streptozotocin Induce Polycystic Ovary Syndrome Features in Mice Ryu, Youngjae Kim, Yong Jin Kim, Yoon Young Kim, Jungwoo Kim, Sung Woo Kim, Hoon Ku, Seung Yup Int J Mol Sci Article 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. MDPI 2021-01-28 /pmc/articles/PMC7865447/ /pubmed/33525535 http://dx.doi.org/10.3390/ijms22031299 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ryu, Youngjae Kim, Yong Jin Kim, Yoon Young Kim, Jungwoo Kim, Sung Woo Kim, Hoon Ku, Seung Yup Consecutive Low Doses of Streptozotocin Induce Polycystic Ovary Syndrome Features in Mice |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865447/ https://www.ncbi.nlm.nih.gov/pubmed/33525535 http://dx.doi.org/10.3390/ijms22031299 |
work_keys_str_mv | AT ryuyoungjae consecutivelowdosesofstreptozotocininducepolycysticovarysyndromefeaturesinmice AT kimyongjin consecutivelowdosesofstreptozotocininducepolycysticovarysyndromefeaturesinmice AT kimyoonyoung consecutivelowdosesofstreptozotocininducepolycysticovarysyndromefeaturesinmice AT kimjungwoo consecutivelowdosesofstreptozotocininducepolycysticovarysyndromefeaturesinmice AT kimsungwoo consecutivelowdosesofstreptozotocininducepolycysticovarysyndromefeaturesinmice AT kimhoon consecutivelowdosesofstreptozotocininducepolycysticovarysyndromefeaturesinmice AT kuseungyup consecutivelowdosesofstreptozotocininducepolycysticovarysyndromefeaturesinmice |