Effect of Methadone Treatment During Pregnancy on the Fetal Testes and Hypothalamus in Rats

Animal and human data have shown that methadone (M) treatment in adults causes a significant decrease in blood testosterone (T) levels. Whether M treatment of rats during pregnancy will affect fetal T levels is the subject of this study. The results show that M treatment (5 mg/kg BW) of rats from Day 14 through 19 of gestation causes a significant decrease (P<0.05) in fetal blood T and Δ4-androstenedione (Δ4-AD) levels in males. Higher dose levels of M (7.5, 10 and 20 mg/kg BW) caused no further significant decreases in T and Δ4-AD levels. M treatment had no effect on T and Δ4-AD levels in the female fetuses. Also, the ability of the fetal testes to synthesize T and of the hypothalamus to aromatize T to estrogen (E) were not affected by M treatment (10 mg/kg BW). The specificity of the M effect on male fetal T and Δ4-AD levels was confirmed because naloxone (anti-M drug) antagonized the M effect. It is concluded that the decrease in male fetal T and Δ4-AD levels in M treated mothers is not due to a direct effect of M on the fetal testes but to an indirect effect mediated elsewhere.