title: In vitro re-expression of the aryl hydrocarbon receptor (Ahr) in cultured Ahr-deficient mouse antral follicles partially restores the phenotype to that of cultured wild-type mouse follicles.
abstract: BACKGROUND
  The aryl hydrocarbon receptor (AHR) mediates the toxic effects of various endocrine disrupting chemicals. In female mice, global deletion of the Ahr (AhrKO) results in slow growth of ovarian antral follicles. No studies, however, have examined whether injection of the Ahr restores the phenotypes of cultured AhrKO ovarian antral follicles to wild-type levels.
  
  
  METHODS
  We developed a system to construct a recombinant adenovirus containing the Ahr to re-express the Ahr in AhrKO granulosa cells and whole antral follicles. We then compared follicle growth and levels of factors in the AHR signaling pathway (Ahr, Ahrr, Cyp1a1, and Cyp1b1) in wild-type, AhrKO, and Ahr re-expressed follicles. Further, we compared the response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in wild-type, AhrKO, and Ahr re-expressed follicles.
  
  
  RESULTS
  Ahr injection into AhrKO follicles partially restored their growth pattern to wild-type levels. Further, Ahr re-expressed follicles had significantly higher levels of Ahr, Ahrr, Cyp1a1, and Cyp1b1 compared to wild-type follicles. Upon TCDD treatment, only Cyp1a1 levels were significantly higher in Ahr re-expressed follicles compared to the levels in wild-type follicles.
  
  
  CONCLUSIONS
  Our system of re-expression of the Ahr partially restores follicle growth and transcript levels of factors in the AHR signaling pathway to wild-type levels.
authors.affiliation: Department of Comparative Biosciences, University of Illinois, Urbana, IL, USA. Electronic address: zivgal1@illinois.edu.
authors.forename: A
authors.initials: A
authors.lastname: Ziv-Gal
authors.affiliation: Department of Comparative Biosciences, University of Illinois, Urbana, IL, USA. Electronic address: lgao@illinois.edu.
authors.forename: L
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Comparative Biosciences, University of Illinois, Urbana, IL, USA. Electronic address: bekarma@gmail.com.
authors.forename: B N
authors.initials: BN
authors.lastname: Karman
authors.affiliation: Department of Comparative Biosciences, University of Illinois, Urbana, IL, USA. Electronic address: jflaws@illinois.edu.
authors.forename: J A
authors.initials: JA
authors.lastname: Flaws
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; C484722:Ahr protein, mouse; C117300:Ahrr protein, mouse; C585498:Cyp1b1 protein, mouse
keywords: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD); Adenovirus; Ahr-deficient mouse (AhrKO); Aryl hydrocarbon receptor (AHR); Mouse; Ovary