The present trend of increasing paternal age is accompanied by concerns for the development of complex multigene diseases (e.g., @entity2438 and @entity161 ) in progeny. Recent studies have established strong correlations between male age, increased oxidative stress, @entity393 , and structural aberrations of chromatin and DNA in spermatozoa. We tested the hypothesis that increasing age would result in altered gene expression relating to oxidative stress and DNA damage/repair in germ cells. To test this hypothesis, pachytene spermatocytes and round spermatids were isolated from Brown Norway (BN) @entity35 at 4 (young) and 18 (aged) mo of age. Microarray analysis was used to compare gene expression between the groups. The probe sets with significantly altered expression were linked to DNA damage/repair and oxidative stress in pachytene spermatocytes but not in round spermatids. Further analysis of pachytene spermatocytes demonstrated that genes involved in the base excision repair (BER) and @entity377 excision repair (NER) pathways were specifically altered. Quantitative RT-PCR confirmed that NER genes were upregulated (>1.5-fold), whereas BER genes were downregulated (>1.5-fold). At the protein level the members of the BER pathway were also altered by up to 2.3-fold; levels of NER proteins remained unchanged. Furthermore, there was an increase in @entity20821 ( @entity20821 ) immunoreactivity in testes from aged males and in the number of spermatozoa positive for @entity20821 . In conclusion, aging is associated with differential regulation of DNA repair pathways with a decrease in the BER pathway leading to deficient repair of @entity20821 lesions in germ cells and spermatozoa.

Aging results in differential regulation of DNA repair pathways in pachytene spermatocytes in the Brown XXXX .

@entity20821 :: ('MESH:C067134', 'Chemical') :: ['8-oxo-dG', "8-oxo-2'-deoxyguanosine", '8-oxodG'] @entity2438 :: ('MESH:D001321', 'Disease') :: ['autism'] @entity377 :: ('CHEBI:36976', 'Chemical') :: ['nucleotide'] @entity161 :: ('MESH:D012559', 'Disease') :: ['schizophrenia'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity393 :: ('MESH:D034381', 'Disease') :: ['decreased sperm quality']
@entity35 :: (10116,Species) :: ['Norway rat']
