Ovary

The Aryl Hydrocarbon Receptor Affects Mouse Ovarian Follicle Growth Via Mechanisms Involving Estradiol Regulation and Responsiveness

Abstract
The aryl hydrocarbon receptor (AHR) is a known transcription factor. Although studies indicate that Ahr deficient (AhRKO) mice have defects in female reproduction, only a few studies have examined the role of the AHR in the ovary. These studies suggested, but did not directly test, that AhRKO mice may have slower follicular growth compared to wild-type (WT) mice. Therefore, the first objective of this study was to examine whether AhRKO follicles grow slower than WT follicles and, if so, to determine whether the mechanism by which the Ahr affects follicular growth is through effects on antrum size, granulosa cell proliferation, and regulators of cell cycle progression. Since estradiol (E₂) is critical for normal growth of ovarian follicles, the second objective of this study was to determine the role of the Ahr in regulating E₂ production and responsiveness. Lastly, the third objective of this study was to determine whether E₂ replacement restores follicular growth of AhRKO follicles to WT levels in vitro. Our results show that AhRKO follicles grow slower than WT follicles in vitro. While AhRKO and WT follicles have similar antrum sizes, AhRKO follicles have decreased granulosa cell proliferation and reduced mRNA and protein levels of cell cycle regulators compared to WT follicles. Further, AhRKO mice have lower serum and follicle-produced E₂ levels, and decreased Esr1 and Esr2 mRNA levels compared to WT mice. Finally, E₂ treatment of AhRKO follicles restored follicular growth to WT levels in vitro. Collectively, these findings suggest that the AHR affects follicular growth via mechanisms involving E₂ regulation and responsiveness.

Key words: Ovary • Toxicology • Estradiol • Estradiol receptor • Follicle

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