One of the major causes of defective sperm function is oxidative stress, which not only disrupts the integrity of sperm DNA but also
limits the fertilizing potential of these cells as a result of collateral damage to proteins and lipids in the sperm plasma membrane.
The origins of such oxidative stress appear to involve the sperm mitochondria, which have a tendency to generate high levels of
superoxide anion as a prelude to entering the intrinsic apoptotic cascade. Unfortunately, these cells have very little capacity to
respond to such an attack because they only possess the fi rst enzyme in the base excision repair (BER) pathway, 8-oxoguanine
glycosylase 1 (OGG1). The latter successfully creates an abasic site, but the spermatozoa cannot process the oxidative lesion further
because they lack the downstream proteins (APE1, XRCC1) needed to complete the repair process. It is the responsibility of the
oocyte to continue the BER pathway prior to initiation of S-phase of the fi rst mitotic division. If a mistake is made by the oocyte
at this stage of development, a mutation will be created that will be represented in every cell in the body. Such mechanisms may
explain the increase in childhood cancers and other diseases observed in the offspring of males who have suffered oxidative stress
in their germ line as a consequence of age, environmental or lifestyle factors. The high prevalence of oxidative DNA damage in the
spermatozoa of male infertility patients may have implications for the health of children conceived in vitro and serves as a driver
for current research into the origins of free radical generation in the germ line.

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