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

被引:26
作者
Kajihara, Takeshi [1 ]
Uchino, Satomi [1 ]
Suzuki, Motoharu [1 ]
Itakura, Atsuo [1 ]
Brosens, Jan J. [2 ]
Ishihara, Osamu [1 ]
机构
[1] Saitama Med Univ, Dept Obstet & Gynecol, Moroyama, Saitama 3500495, Japan
[2] Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, Hammersmith Hosp, London, England
关键词
Apoptosis; Follicle; Insulin; Ovary; Granulosa cells; GRANULOSA-CELL APOPTOSIS; POLYCYSTIC-OVARY; INSULIN; FATTY; MICE; SUPPRESSION; MUTATION;
D O I
10.1007/s00795-009-0466-7
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:216 / 221
页数:6
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