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Increased ovarian follicle atresia in obese Zucker rats is associated with enhanced expression of the forkhead transcription factor FOXO1

Medical Molecular Morphology volume 42, pages 216–221 (2009)Cite this article

Abstract

It is well established that hyperinsulinemia, resulting from insulin resistance, plays a role in the pathophysiology of polycystic ovary syndrome (PCOS). The aim of this study was to investigate if ovarian follicular development and atresia are impaired in obese hyperinsulinemic (fa/fa) Zucker rats. To gain insight into the molecular mechanism of follicular atresia, we also examined the expression and localization of forkhead transcription factor FOXO1, a major regulator of cell fate decisions such as differentiation, cell-cycle arrest, and cell death. Serum insulin but not gonadotropin levels were significantly higher in obese (fa/fa) rats when compared to lean controls. Total ovarian follicle number and the percentage of atretic follicles were also significantly increased in obese (fa/fa) rats. Follicle atresia was associated with nuclear accumulation of FOXO1 transcription factor in TUNEL-positive granulosa cells. These results suggest a role for FOXO1 in granulosa cell apoptosis and increased ovarian follicle atresia associated with hyperinsulinemia.

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Affiliations

  1. Department of Obstetrics and Gynecology, Saitama Medical University, 38 Morohongo, Moroyama, Iruma-gun, Saitama, 350-0495, Japan

    Takeshi Kajihara, Satomi Uchino, Motoharu Suzuki, Atsuo Itakura & Osamu Ishihara

  2. Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, London, UK

    Jan J. Brosens

Authors
  1. Takeshi Kajihara
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  2. Satomi Uchino
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  3. Motoharu Suzuki
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  4. Atsuo Itakura
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  5. Jan J. Brosens
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  6. Osamu Ishihara
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Correspondence to Takeshi Kajihara.

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Kajihara, T., Uchino, S., Suzuki, M. et al. Increased ovarian follicle atresia in obese Zucker rats is associated with enhanced expression of the forkhead transcription factor FOXO1. Med Mol Morphol 42, 216–221 (2009). https://doi.org/10.1007/s00795-009-0466-7

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  • DOI: https://doi.org/10.1007/s00795-009-0466-7

Key words

  • Apoptosis
  • Follicle
  • Insulin
  • Ovary
  • Granulosa cells