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Physiological Role of the Aryl
Hydrocarbon Receptor in the Ovary
Jamie C. Benedict
School of Medicine, University of Maryland, Baltimore
The aryl hydrocarbon receptor (AhR) is found in a variety of cells in a variety of tissue types in many species. The major purpose of this receptor is to regulate the toxicity of various environmental chemicals such as 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). Upon binding of a chemical such as TCDD to the AhR, a cascade of events follows which leads to the transcription of various metabolic genes.
To date the physiological role of the AhR is not completely understood. Studies using mice deficient in AhR have shown that it is vital for the development and function of the liver and immune system. Recently, it has been suggested that the AhR may be involved in the physiology of the female reproductive system. Specifically, we have preliminary data suggesting that the AhR is involved in maintaining a normal number of antral follicles in the ovary. However, knowledge is lacking in the mechanism by which the AhR regulates the number of follicles in the developing ovary. Thus, we propose to test the hypothesis that the AhR may either increase the growth of small follicles to the antral stage or decrease the rate of atresia in antral follicles. To test this hypothesis, we will complete the following aims: 1) determine if the AhR regulates follicular growth and/or death, and 2) evaluate whether the AhR regulates ovarian growth and/or death via a direct or indirect mechanism.
To complete these aims, we will evaluate growth and death of ovarian follicles using mice deficient in the AhR (AhRKO). Specifically, we will measure rates of growth and death of ovarian follicles using both in vivo and in vitro models. We will also evaluate the mechanism by which the AhR affects the ovary by measuring hormone levels in the blood and transplanting ovaries from AhRKO mice into wildtype (WT) recipient mice.
The results of this study will help determine the role of the AhR in the developing ovary and identify whether such effects are mediated by a direct or indirect mechanism in the ovary. Such data will increase our understanding of the female reproductive system. In turn, this understanding may provide clues about ovarian development in women.
