Spermatogenesis is not impaired in a nucleotide excision repair-deficient min mouse model with or without neonatal mutagen treatment.

Abstract

Mice deficient in the xeroderma pigmentosum group A gene (Xpa) exhibit impaired nucleotide excision repair (NER) and are expected to accumulate bulky DNA adducts when subjected to certain compounds (eg, heterocyclic amines). Multiple intestinal neoplasia (Min) mice (B6(Min)(/+)) are particularly sensitive to low concentrations of mutagenic compounds in food. They develop intestinal tumors spontaneously, and the number and size of the tumors increase following exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which humans are exposed to via fried food. We previously reported that NER is inefficient in adult testicular cells. Reduced NER (genetic deficiency; Xpa(-/-)) is expected to represent risk factors for PhIP-induced genotoxicity and could possibly disturb spermatogenesis, particularly in B6(Min)(/+) mice. We therefore studied spermatogenesis in mice with combinations of Xpa and Min or wild-type genotypes 11 weeks after exposure to PhIP on days 3 to 6. Fewer offspring were obtained from B6(Min)(/+)Xpa(-/-) than from B6(Min)(/+)Xpa(+/+) or B6(Min)(/+)Xpa(+/-). Distributions of the different testicular cell types, indicative of normal spermatogenesis and relative testes weights, did not differ significantly in PhIP-exposed or unexposed mice regardless of their genotypes. We conclude that the removal of bulky DNA adducts does not seem to be essential for normal spermatogenesis.