title: Remarkable features of ovarian morphology and reproductive hormones in insulin-resistant Zucker fatty (fa/fa) rats.
abstract: BACKGROUND
  Zucker fatty (fa/fa) rats are a well-understood model of obesity and hyperinsulinemia. It is now thought that obesity/hyperinsulinemia is an important cause of endocrinological abnormality, but to date there have been no reports on the changes in ovarian morphology or the ovarian androgen profile in rat models of obesity and insulin resistance.
  
  
  METHODS
  In this study we investigated the effects of obesity and hyperinsulinemia on ovarian morphology and the hormone profile in insulin-resistant Zucker fatty rats (5, 8, 12 and 16 weeks of age, n = 6-7).
  
  
  RESULTS
  Ovaries from 5-week-old fatty rats had significantly greater total and atretic follicle numbers, and higher atretic-to-total follicle ratios than those from lean rats. Ovaries from 12- and 16-week-old fatty rats showed interstitial cell hyperplasia and numerous cysts with features of advanced follicular atresia. In addition, serum testosterone and androstenedione levels significantly declined in fatty rats from age 8 to 16 weeks, so that fatty rats showed significantly lower levels of serum testosterone (12 and 16 weeks) and androstenedione (all weeks) than lean rats. This may reflect a reduction of androgen synthesis during follicular atresia. Serum adiponectin levels were high in immature fatty rats, and although the levels declined significantly as they matured, it remained significantly higher in fatty rats than in lean rats. On the other hand, levels of ovarian adiponectin and its receptors were significantly lower in mature fatty rats than in lean mature rats or immature fatty rats.
  
  
  CONCLUSIONS
  Our findings indicate that ovarian morphology and hormone profiles are significantly altered by the continuous insulin resistance in Zucker fatty rats. Simultaneously, abrupt reductions in serum and ovarian adiponectin also likely contribute to the infertility seen in fatty rats.
authors.affiliation: Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South 1 West 16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Honnma
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Endo
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kiya
authors.forename: Ayumi
authors.initials: A
authors.lastname: Shimizu
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Nagasawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Baba
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujimoto
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Henmi
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Kitajima
authors.forename: Kengo
authors.initials: K
authors.lastname: Manase
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ishioka
authors.forename: Eiki
authors.initials: E
authors.lastname: Ito
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000502:physiology; D030762:Estrous Cycle / Q000097:blood / Q000378:metabolism / Q000502:physiology; D005260:Female; D015870:Gene Expression; D042341:Gonadal Hormones / Q000097:blood*; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D009765:Obesity / Q000097:blood* / Q000235:genetics / Q000473:pathology*; D009929:Organ Size; D010053:Ovary / Q000473:pathology*; D051381:Rats; D011924:Rats, Zucker; D013851:Thinness / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D052242:Adiponectin; D042341:Gonadal Hormones