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

The aryl hydrocarbon receptor (AhR), so-designated based on the ability of the protein to bind with and be activated by polycyclic aromatic hydrocarbo ns (PAH) and related halogenated hydrocarbons, is part of an emerging famil y of ligand-activated transcriptional regulators that are distinct from the steroid-thyroid hormone receptor superfamily. Once bound by ligand, the Ah R interacts with the AhR nuclear translocator (ARNT) protein to form the ar yl hydrocarbon receptor complex (AHRC). Both subunits of the AHRC contain s equences corresponding to basic helix-loop-helix domains, a motif that is s hared by a number of other dimeric transcription factors. Although the natu ral ligand(s) for the AhR remains to be elucidated, to date over fifteen ge nes, including enzymes, growth factors and other transcription factors, hav e been identified as potential targets for transcriptional regulation by th e chemically-activated AHRC. In the ovary, PAH exposure is known to cause d estruction 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 deve lopment. Histomorphometric analysis of serial ovarian sections revealed a t wo-fold higher number of primordial follicles in Ahr-null versus wild-type females at day 4 postpartum. This phenotype likely results from a cell-intr insic death defect in the developing germ line since AhR-deficiency attenua ted the magnitude of oocyte apoptosis in fetal ovaries cultured without hor monal support for 72 h. We propose that the AhR, activated by an as yet unk nown endogenous ligand(s), serves to regulate the size of the oocyte reserv e endowed at birth by affecting germ cell death during female gametogenesis .