Role of the aryl hydrocarbon receptor in the development of control and 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed male mice

Experiments were conducted to determine the role of the aryl hydrocarbon re ceptor (AhR) in the development of control and 2,3,7,8-tetrachlorodibenzo-p -dioxin (TCDD)exposed C57B1/6 male mice. Male and female mice heterozygous for the AhR (Ahr(+/-)) were mated, and pregnant females were dosed orally o n gestation day 13 with corn oil vehicle or TCDD (5 mug/kg). Pups were necr opsied on postnatal day (PND) 21, 35, and 90. Comparison of vehicle-exposed wild-type (Ahr(+/+)) pups with vehicle-exposed AhR knockout (AhRKO; Ahr(-/ -)) pups confirmed and extended previous reports that development of the li ver, heart, spleen, thymus, and kidney is affected by absence of the AhR. L ung, submandibular gland, testis, and epididymis weights were also affected , indicating that the AhR plays a role in normal development of these organ s as well. The presence or absence of the AhR had no effect on the incidenc e of hydronephrosis, daily sperm production, or cauda epididymal sperm numb ers in vehicle-exposed mice. TCDD caused numerous effects in wild-type mice that were absent in AhRKO mice; specifically, hydronephrosis, increases in relative liver and heart weight, decreases in absolute heart and lung weig ht, and decreases in absolute and relative thymus, submandibular gland, epi didymis, and testis weight. In several cases, TCDD produced one effect in w ild-type mice (reductions in body weight and absolute thymus, submandibular gland, and epididymis weight on PND 21; and reductions in absolute and rel ative submandibular gland and absolute testis weight on PND 35) but caused the opposite effect in AhRKO mice. In yet other cases (reduced relative spl een weight on PND 21 and reductions in absolute and relative thymus weight on PND 35), TCDD produced similar effects in wildtype and AhRKO mice. There were also cases in which TCDD significantly affected AhRKO mice without si gnificantly altering the same endpoint in wild-type mice; absolute liver, l ung, and kidney weight were increased and relative submandibular gland weig ht was decreased on PND 21; relative heart weight was reduced and absolute lung weight increased on PND 35; and relative liver weight was decreased on PND 90. Although many effects of TCDD required the presence of the AhR, th ese results provide evidence either for multiple forms of the AhR in mice ( one or more of which are still present in AhRKO mice), or for AhR-independe nt effects of low-level TCDD exposure.