title: Increased ovarian follicle atresia in obese Zucker rats is associated with enhanced expression of the forkhead transcription factor FOXO1.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Saitama Medical University, 38 Morohongo, Moroyama, Iruma-gun, Saitama 350-0495, Japan. kajihara@saitama-med.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kajihara
authors.forename: Satomi
authors.initials: S
authors.lastname: Uchino
authors.forename: Motoharu
authors.initials: M
authors.lastname: Suzuki
authors.forename: Atsuo
authors.initials: A
authors.lastname: Itakura
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Brosens
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishihara
mesh_terms: D000818:Animals; D017209:Apoptosis; D005260:Female; D005496:Follicular Atresia / Q000502:physiology*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006107:Granulosa Cells / Q000166:cytology / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009765:Obesity; D006080:Ovarian Follicle / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011924:Rats, Zucker; D015854:Up-Regulation; D000071161:Forkhead Box Protein O1
chemical_list: D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1