title: The aryl hydrocarbon receptor, a basic helix-loop-helix transcription factor of the PAS gene family, is required for normal ovarian germ cell dynamics in the mouse.
abstract: The aryl hydrocarbon receptor (AhR), so-designated based on the ability of the protein to bind with and be activated by polycyclic aromatic hydrocarbons (PAH) and related halogenated hydrocarbons, is part of an emerging family of ligand-activated transcriptional regulators that are distinct from the steroid-thyroid hormone receptor superfamily. Once bound by ligand, the AhR interacts with the AhR nuclear translocator (ARNT) protein to form the aryl hydrocarbon receptor complex (AHRC). Both subunits of the AHRC contain sequences corresponding to basic helix-loop-helix domains, a motif that is shared by a number of other dimeric transcription factors. Although the natural ligand(s) for the AhR remains to be elucidated, to date over fifteen genes, including enzymes, growth factors and other transcription factors, have been identified as potential targets for transcriptional regulation by the chemically-activated AHRC. In the ovary, PAH exposure is known to cause destruction of oocytes within immature follicles, implying that one function of the AhR is to mediate cell death signaling in the female germ line. To assess this possibility, we explored AhR expression patterns in the murine ovary, and then determined the impact of AhR-deficiency (gene knockout) on female germ cell dynamics. Immunohistochemical analysis of ovaries of wild-type female mice indicated that AhR protein was abundantly and exclusively expressed in oocytes and granulosa cells of follicles at all stages of development. Histomorphometric analysis of serial ovarian sections revealed a two-fold higher number of primordial follicles in Ahr-null versus wild-type females at day 4 postpartum. This phenotype likely results from a cell-intrinsic death defect in the developing germ line since AhR-deficiency attenuated the magnitude of oocyte apoptosis in fetal ovaries cultured without hormonal support for 72 h. We propose that the AhR, activated by an as yet unknown endogenous ligand(s), serves to regulate the size of the oocyte reserve endowed at birth by affecting germ cell death during female gametogenesis.
authors.affiliation: Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical School, Boston 02114, USA.
authors.forename: R
authors.initials: R
authors.lastname: Robles
authors.forename: Y
authors.initials: Y
authors.lastname: Morita
authors.forename: K K
authors.initials: KK
authors.lastname: Mann
authors.forename: G I
authors.initials: GI
authors.lastname: Perez
authors.forename: S
authors.initials: S
authors.lastname: Yang
authors.forename: T
authors.initials: T
authors.lastname: Matikainen
authors.forename: D H
authors.initials: DH
authors.lastname: Sherr
authors.forename: J L
authors.initials: JL
authors.lastname: Tilly
mesh_terms: D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D005260:Female; D006107:Granulosa Cells / Q000502:physiology; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D010053:Ovary / Q000166:cytology / Q000502:physiology*; D010063:Ovum / Q000502:physiology*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors