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 AdAhr 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. Conclusion 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.

Altered histone abundance as a mode of ovotoxicity during 7,12-dimethylbenz[a]anthracene exposure with additive influence of obesity

“…The PAH group of chemicals are ubiquitous, and PAH exposure can induce dysfunction in the female reproductive system, including ovarian follicle destruction, impaired steroidogenesis, folliculogenesis, embryo transportation, and implantation and endometrial function [ 54–57 ]. The ovary expresses chemical biotransformation enzymes [ 58–61 ] which can bioactivate DMBA to a genotoxic and ovotoxic metabolite, 3,4-diol-1,2-epoxide [ 37 ]. The electrophilic property of this epoxide metabolite reacts with DNA, which acts as a nucleophile, leading to DNA adduct formation [ 29 ].…”

Indoleamine 2, 3-Dioxygenase Promotes Aryl Hydrocarbon Receptor-Dependent Differentiation Of Regulatory B Cells in Lung Cancer

“…To further ascertain the role of AhR, we determined the expression of AhR and its target gene Cyp1A1 by qRT-PCR in cells impairs L-Kyn induced Breg differentiation. Purified CD19 + B cells from splenocytes of naïve AhR -/were cultured to perform ex-vivo experiments followed by LPS+L-Kyn stimulation (53). Interestingly LPS+ L-Kyn was unable to induce Breg differentiation in AhR -/-B cells, and in addition, a significant reduction in Bregs frequency was also observed in AhR -/compared to WT control mice (Figure 5A).…”