Kajihara Takeshi, Uchino Satomi, Suzuki Motoharu, Itakura Atsuo, Brosens Jan J, Ishihara Osamu
Department of Obstetrics and Gynecology, Saitama Medical University, 38 Morohongo, Moroyama, Iruma-gun, Saitama 350-0495, Japan.
Med Mol Morphol. 2009 Dec;42(4):216-21. doi: 10.1007/s00795-009-0466-7. Epub 2009 Dec 24.
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.
胰岛素抵抗导致的高胰岛素血症在多囊卵巢综合征（PCOS）的病理生理过程中起作用，这一点已得到充分证实。本研究的目的是调查肥胖高胰岛素血症（fa/fa）Zucker大鼠的卵巢卵泡发育和闭锁是否受损。为深入了解卵泡闭锁的分子机制，我们还检测了叉头转录因子FOXO1的表达和定位，FOXO1是细胞命运决定（如分化、细胞周期停滞和细胞死亡）的主要调节因子。与瘦素对照组相比，肥胖（fa/fa）大鼠的血清胰岛素水平显著升高，但促性腺激素水平未升高。肥胖（fa/fa）大鼠的卵巢卵泡总数和闭锁卵泡百分比也显著增加。卵泡闭锁与TUNEL阳性颗粒细胞中FOXO1转录因子的核积累有关。这些结果表明FOXO1在颗粒细胞凋亡以及与高胰岛素血症相关的卵巢卵泡闭锁增加中起作用。
