title: The ability of the aryl hydrocarbon receptor to regulate ovarian follicle growth and estradiol biosynthesis in mice depends on stage of sexual maturity.
abstract: The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of environmental chemicals and regulates many physiological functions, including processes in female reproduction. Previous studies demonstrated that Ahr deletion leads to slow ovarian follicle growth because of impaired estradiol production and reduced gonadotropin responsiveness in prepubertal mice. These studies, however, did not determine how Ahr deletion impairs estradiol production or whether the effects of Ahr deletion on follicle growth and estradiol production persist in adulthood. Thus, the present study evaluated the effect of Ahr deletion on steroid precursors in the estradiol biosynthesis pathway. Furthermore, this study evaluated follicle growth and estradiol biosynthesis in wild-type (WT) and Ahr knockout (AhrKO) antral follicles at different stages of sexual maturity. AhrKO antral follicles from prepubertal mice had slower growth, produced lower estradiol levels, and had reduced cyclin D2 (Ccnd2) expression compared to WT follicles. AhrKO follicles from adult mice, however, produced higher androgen levels and expressed higher levels of Ccnd2 compared to WT follicles. Furthermore, AhrKO follicles from adult mice had growth to that of WT follicles. These findings suggest that the AHR regulates follicle growth by altering factors involved in the estradiol biosynthesis pathway as well as key regulators of follicle growth and that this role of AHR depends on stage of sexual maturity.
authors.affiliation: Department of Comparative Biosciences, University of Illinois, Urbana-Champaign, Urbana, Illinois 61802, USA.
authors.forename: Isabel
authors.initials: I
authors.lastname: Hernandez-Ochoa
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Barnett-Ringgold
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Dehlinger
authors.forename: Rupesh K
authors.initials: RK
authors.lastname: Gupta
authors.forename: Traci C
authors.initials: TC
authors.lastname: Leslie
authors.forename: Katherine F
authors.initials: KF
authors.lastname: Roby
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Flaws
mesh_terms: D000375:Aging; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D002452:Cell Count; D056742:Cyclin D2 / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D009924:Organ Culture Techniques; D006080:Ovarian Follicle / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000502:physiology*; D011962:Receptors, FSH / Q000235:genetics / Q000378:metabolism; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012741:Sexual Maturation / Q000502:physiology*; D045165:Testosterone Congeners / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D056742:Cyclin D2; D004958:Estradiol; D012333:RNA, Messenger; D011944:Receptors, Androgen; D018336:Receptors, Aryl Hydrocarbon; D011962:Receptors, FSH; D011974:Receptors, LH; D045165:Testosterone Congeners; C484722:Ahr protein, mouse; C486196:Ccnd2 protein, mouse