title: Androstenedione induces abnormalities in morphology and function of developing oocytes, which impairs oocyte meiotic competence.
abstract: OBJECTIVE
  To obtain insight into the effects of androstenedione on ovarian folliculogenesis and oogenesis.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  St. Marianna University School of Medicine.
  
  
  METHODS
  Prepubertal (14-day-old) BDF1 female mice.
  
  
  METHODS
  Early secondary follicles were isolated from the ovaries and were cultured individually in vitro with or without androstenedione (10(-11) to 10(-5) M) for 12 days. Thereafter, the follicles were treated with hCG and epidermal growth factor (EGF).
  
  
  METHODS
  Diameters and morphology of follicles and oocytes; E(2) and P secretion; and chromatin configuration and expression of growth differentiation factor 9 (GDF9) in oocytes were examined.
  
  
  RESULTS
  Early secondary follicles developed to the preovulatory stage. Androstenedione treatments increased the follicle diameters, reduced survival rates of follicles, and promoted the formation of follicles with abnormal morphology, including misshapen oocyte. The secretion of E(2) and P was significantly higher in androstenedione-exposed follicles. Androstenedione prevented the alteration in chromatin configuration and reduced oocyte GDF9 expression. When follicles cultured with androstenedione were treated with hCG and EGF, the first polar body exclusion, chromosome alignment on metaphase plate, and spindle assembly were inhibited in the oocytes.
  
  
  CONCLUSIONS
  These results demonstrate that excess androgen induces abnormalities in the morphology and function of developing oocytes, which impairs oocyte meiotic competence.
authors.affiliation: Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Tarumi
authors.forename: Sanae
authors.initials: S
authors.lastname: Tsukamoto
authors.forename: Yuki
authors.initials: Y
authors.lastname: Okutsu
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Horiuchi
authors.forename: Masanori T
authors.initials: MT
authors.lastname: Itoh
authors.forename: Bunpei
authors.initials: B
authors.lastname: Ishizuka
mesh_terms: D000735:Androstenedione / Q000633:toxicity*; D000818:Animals; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism; D005260:Female; D055429:Growth Differentiation Factor 9 / Q000378:metabolism; D008540:Meiosis / Q000187:drug effects*; D051379:Mice; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009866:Oogenesis / Q000187:drug effects*; D006080:Ovarian Follicle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011374:Progesterone / Q000378:metabolism; D013997:Time Factors
chemical_list: D006063:Chorionic Gonadotropin; C525898:Gdf9 protein, mouse; D055429:Growth Differentiation Factor 9; D000735:Androstenedione; D011374:Progesterone; D004958:Estradiol; D004815:Epidermal Growth Factor