Recent advances in understanding of male infertility have implicated two ma
jor causative factors, oxidative stress and Y chromosome deletions. A major
cause of oxidative stress appears to be the high rate of reactive oxygen s
pecies generation associated with the retention of excess residual cytoplas
m in the sperm midpiece. Other possible causes include the redox cycling of
xenobiotics, and antioxidant depletion or apoptosis. Oxidative stress indu
ces peroxidative damage in the sperm plasma membrane and DNA damage in both
the mitochondrial and nuclear genomes. Nuclear DNA damage in the germ line
of the father may be associated with pathology in the offspring, including
childhood cancer and infertility. Gene deletions on the non-recombining re
gion of the Y chromosome account for the infertility observed in about 15%
of patients with azoospermia and 5-10% of subjects with severe oligozoosper
mia. The Y chromosome is particularly susceptible to gene deletions because
of the inability of the haploid genome to deploy recombination repair in r
etrieving lost genetic information. Aberrant recombination, defective chrom
atin packaging, abortive apoptosis and oxidative stress may all be involved
in the aetiology of DNA damage in the germ line. The factors responsible f
or Y chromosome deletions in spermatozoa remain unresolved but may be one f
acet of a central reproductive problem: controlling the amount of oxidative
stress experienced by germ cells during their differentiation and maturati
on in the male reproductive tract.