Murine oocyte destruction following intraovarian treatment with 3‐methylcholanthrene or 7,12‐dimethylbenz(a)anthracene: Protection by alpha‐naphthoflavone

Abstract

Bilateral or unilateral intraovarian injection with the polycyclic aromatic hydrocarbons 3‐methylcholanthrene (3‐MC), or 7,12‐dimethylbenz(a)anthracene (DMBA) destroys oocytes in C57BL/6N and DBA/2N mice. The threshold for small oocyte destruction following bilateral intraovarian treatment with 3‐MC was between 0.1 and 1 μg/ovary in both DBA/2N and C57BL/6N mice. After intraovarian treatment with DMBA, a more potent ovotoxin, the thresholds for small oocyte destruction were between 0.01 and 0.1 μg/ovary. Calculated ED₅₀'s for small oocyte destruction following bilateral intraovarian treatment with 3‐MC were C57BL/6N, 0.33 μg/ovary; DBA/2N, 1.02 μg/ovary—for DMBA the ED₅₀'s were C57BL/6N, 0.11 μg/ovary; DBA/2N, 0.03 μg/ovary. Unilateral intraovarian treatment also destroyed oocytes in the treated ovary. Treatment with intraperitoneal alpha‐naphthoflavone (ANF), a competitive inhibitor of polycyclic aromatic hydrocarbon metabolism by microsomal monooxygenases, inhibited oocyte destruction. Intraovarian treatment with ANF decreased oocyte destruction produced by intraovarian DMBA. These data suggest that both 3‐MC and DMBA are indirect acting ovotoxins requiring metabolic activation before oocyte destruction occurs. In addition, these data also suggest that the ovary contains the enzymes necessary to biotransform xenobiotics like 3‐MC and DMBA to ovotoxic metabolites. Metabolic activation of xenobiotics to reactive products within the ovary may represent a special threat to the integrity of oocyte DNA.