title: Western-style diet, with and without chronic androgen treatment, alters the number, structure, and function of small antral follicles in ovaries of young adult monkeys.
abstract: OBJECTIVE
  To examine the small antral follicle (SAF) cohort in ovaries of adult rhesus monkeys after consumption of a Western-style diet (WSD), with or without chronically elevated androgen levels since before puberty.
  
  
  METHODS
  Cholesterol or T (n = 6 per group) implants were placed SC in female rhesus macaques beginning at 1 year of age (prepubertal), with addition of a WSD (high fat/fructose) at 5.5 years (menarche approximately 2.6 years). Ovaries were collected at 7 years of age. One ovary per female was embedded in paraffin for morphologic and immunohistochemical analyses. The SAFs (<2.5 mm) were dissected from the other ovary obtained at or near menses in a subgroup of females (n = 3 per group) and processed for microarray analyses of the SAF transcriptome. Ovaries of adult monkeys consuming a standard macaque diet (low in fats and sugars) were obtained at similar stages of the menstrual cycle and used as controls for all analyses.
  
  
  METHODS
  Primate research center.
  
  
  METHODS
  Adult, female rhesus monkeys (Macaca mulatta).
  
  
  METHODS
  None.
  
  
  METHODS
  Histologic analyses, SAF counts and morphology, protein localization and abundance in SAFs, transcriptome in SAFs (messenger RNAs [mRNAs]).
  
  
  RESULTS
  Compared with controls, consumption of a WSD, with and without T treatment, increased the numbers of SAFs per ovary, owing to the presence of more atretic follicles. Numbers of granulosa cells expressing cellular proliferation markers (pRb and pH3) was greater in healthy SAFs, whereas numbers of cells expressing the cell cycle inhibitor (p21) was higher in atretic SAFs. Intense CYP17A1 staining was observed in the theca cells of SAFs from WSD with or without T groups, compared with controls. Microarray analyses of the transcriptome in SAFs isolated from WSD and WSD plus T-treated females and controls consuming a standard diet identified 1,944 genes whose mRNA levels changed twofold or more among the three groups. Further analyses identified several gene pathways altered by WSD and/or WSD plus T associated with steroid, carbohydrate, and lipid metabolism, plus ovarian processes. Alterations in levels of several SAF mRNAs are similar to those observed in follicular cells from women with polycystic ovary syndrome.
  
  
  CONCLUSIONS
  These data indicate that consumption of a WSD high in fats and sugars in the presence and absence of chronically elevated T alters the structure and function of SAFs within primate ovaries.
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon. Electronic address: bishopc@ohsu.edu.
authors.forename: Cecily V
authors.initials: CV
authors.lastname: Bishop
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon.
authors.forename: Fuhua
authors.initials: F
authors.lastname: Xu
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon.
authors.forename: Alison Y
authors.initials: AY
authors.lastname: Ting
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon.
authors.forename: Etienne
authors.initials: E
authors.lastname: Galbreath
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon.
authors.forename: Whitney K
authors.initials: WK
authors.lastname: McGee
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Zelinski
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon; Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, Oregon.
authors.forename: Jon D
authors.initials: JD
authors.lastname: Hennebold
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Judy L
authors.initials: JL
authors.lastname: Cameron
authors.affiliation: Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon; Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, Oregon.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Stouffer
mesh_terms: D000367:Age Factors; D000728:Androgens / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D066273:Diet, Western / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D006080:Ovarian Follicle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012741:Sexual Maturation / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome
chemical_list: D000728:Androgens
keywords: Androgen; Western-style diet; metabolism; ovarian function; small antral follicles