Does the increase in sequence mutations suggest that DNA repair is defective?
Obviously, we must address whether the apparent DNA repair defects caused meiotic arrest in those men who show increased number of sequence mutations or are merely a consequence of meiotic arrest due to induction of unknown factors in the testicular microenvironment of men with meiotic arrest. We know that in other organisms, such as mice, deficiencies in some DNA repair enzymes cause meiotic arrest but only when the mice are homozygous for null mutations. Thus, if we are to extend these findings to humans, we expect that if in humans meiotic arrest is caused by DNA repair deficiencies associated with mutations in genes such as PMS1 or MLH1, then some men are mosaic for mutations in these genes. Perhaps, they have one mutant copy in all cells and sustain a second mutation in an early population of spermatogonia. Alternatively, defective DNA repair could be associated with genes that are only required to repair DNA at meiosis and may be inherited in an autosomal or X-linked dominant or
