Expression of the arylhydrocarbon receptor in the peri-implantation period of the mouse uterus and the impact of dioxin on mouse implantation

The arylhydrocarbon receptor (AhR) is a nuclear transcription factor mediating toxic effects of chemicals such as dioxins. The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a member of polyhalogenated aromatic hydrocarbons family, exerts a wide-variety of toxic effects in a tissue- and species-specific manner including the reproduction process. Recently, AhR-mediated direct effects of TCDD on a cell-specific interaction with ovarian steroids have been shown. However, information regarding the effects of TCDD on the mouse implantation is limited. We therefore examined the expression and localization of AhR in the pregnant mouse uterus from 4 to 10 days of gestation (day 4 to day 10) using immunohistochemistry to investigate the effect of TCDD on uterine tissue during the peri-implantation period. Intense AhR expression was detected in the uterine vasculature throughout the periods examined. We also found that implanted blastocysts and their surrounding luminal epithelia and decidualized stroma expressed AhR on day 5. On days 6 and 7, persistent AhR expression was found in the transitional zone between the invading embryonic tissue and decidual tissue. On days 9 to 10, placental vasculature and spongiotrophoblasts displayed AhR immunoreactivity. The administration of TCDD on day 4 decreased the number of surviving implanted embryos on day 7 in a dose-dependent manner. This effect of TCDD was inhibited by the simultaneous administration of an AhR antagonist, alpha-naphthoflavone (alpha-NF). The spatio-temporal expression of AhR during the peri-implantation phase of the mouse uterus may indicate functional roles of this orphan receptor in feto-maternal interactions as well as substantiate the risk of exposure to chemicals such as dioxins during the reproductive period.