Consecutive low doses of streptozotocin induce polycystic ovary syndrome features in mice

Youngjae Ryu, Yong Jin Kim, Yoon Young Kim, Jungwoo Kim, Sung Woo Kim, Hoon Kim, Seung Yup Ku

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Polycystic ovarian syndrome (PCOS) is a common reproductive endocrine disorder in reproductive-age women. Due to its various pathophysiological properties and clinical heterophe-notypes, 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 ad-ministered multiple STZ injections to female C57BL/6 mice (3–4 weeks old) at different concentra-tions: 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. Further-more, 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.

Original languageEnglish
Article number1299
Pages (from-to)1-13
Number of pages13
JournalInternational Journal of Molecular Sciences
Volume22
Issue number3
DOIs
StatePublished - 1 Feb 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Animal models
  • Ovary
  • Polycystic ovary syndrome
  • Streptozotocin
  • Testosterone

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