title: Leptin-deficient (ob/ob) mouse ovaries show fatty degeneration, enhanced apoptosis and decreased expression of steroidogenic acute regulatory enzyme.
abstract: OBJECTIVE
  Leptin-deficient (ob/ob) mice are obese and infertile. Dysfunctions of the ovaries are preferentially related to leptin-deficiency.
  
  
  METHODS
  Morphological and molecular biological obesity-dependent changes in ob/ob ovaries.
  
  
  METHODS
  Ovaries were obtained from three-month-old mice either homozygote (ob/ob) and heterozygote (ob/+) or wild-type (C57BL6, WT) for the investigation by light and electron microscopy, as well as for western blot analysis of lectin-like oxidised low density lipoprotein receptor (LOX-1), Toll-like receptor 4 (TLR4), CD36, cleaved caspase-3, microtubule-associated protein light chain 3 (LC3), and the steroidogenic acute regulatory protein (StAR).
  
  
  RESULTS
  Compared with control ovaries with corpora lutea, ob/ob ovaries lacked corpora lutea, follicular atresia was at a higher rate; lipid droplets accumulated in follicle cells and in the oocyte with damaged mitochondria; the basement membrane of follicles was thickened. LOX-1 and CD36 expressions were comparable for all three groups. Ob/ob ovaries showed significantly higher levels of TLR4 and cleaved caspase-3 than the ones from the control groups. The high LC3-II/I ratio in the WT and ob/+ ovaries was related to the presence of corpora lutea. The StAR protein was lower in the ob/ob ovaries signifying reduced steroidogenesis.
  
  
  CONCLUSIONS
  Excessive lipid storage causes disorders of ovarian function in ob/ob mice. The local lipid overload leads to advanced follicular atresia with apoptosis and defect steroidogenesis. We suggest that the changes in lipid metabolism lead to increased oxidative stress and thereby, they are an important reason of anovulation and infertility.
authors.affiliation: Institute of Anatomy, University of Leipzig, Leipzig, Germany. heike.serke@medizin.uni-leipzig.de
authors.forename: H
authors.initials: H
authors.lastname: Serke
authors.forename: M
authors.initials: M
authors.lastname: Nowicki
authors.forename: J
authors.initials: J
authors.lastname: Kosacka
authors.forename: T
authors.initials: T
authors.lastname: Schröder
authors.forename: N
authors.initials: N
authors.lastname: Klöting
authors.forename: M
authors.initials: M
authors.lastname: Blüher
authors.forename: S
authors.initials: S
authors.lastname: Kallendrusch
authors.forename: K
authors.initials: K
authors.lastname: Spanel-Borowski
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D018955:CD36 Antigens / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D020738:Leptin / Q000172:deficiency* / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D010053:Ovary / Q000378:metabolism / Q000503:physiopathology*; D010750:Phosphoproteins / Q000378:metabolism*; D051127:Scavenger Receptors, Class E / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D018955:CD36 Antigens; D020738:Leptin; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; C495138:Olr1 protein, mouse; D010750:Phosphoproteins; D051127:Scavenger Receptors, Class E; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000098682:Steroidogenic Acute Regulatory Protein