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Preface
Molecular oxidation affects cell function and can lead to cell degeneration or cell
death. Free radicals are a major factor in inducing this oxidation and they can
attack and inactivate or alter the biological activity of molecules such as lipids and
proteins that are essential for cell function. If the detrimental effects of oxidation are
to be avoided, it is essential to understand the modus operandi of the various free
radicals involved in these processes on cellular homeostasis and how this leads to
pathology. Free radicals can be divided in two main groups: the Reactive Oxygen
Species (ROS) and the Reactive Nitrogen Species (RNS).
Free radical biology has implications for many aspects of modern life ranging from
the food industry, where preventing oxidation is crucial to food conservation, to
areas of medical sciences such as neurology, cardiology and, more recently,
reproductive medicine. It is becoming increasingly clear that molecular oxidation
often plays a role in infertility, particularly when reproductive tissues or gametes are
stored or manipulated in vitro.
This thesis focuses on the role of oxidation in male fertility, by studying the
physiology of peroxidation in mammalian sperm, with special emphasis on bovine
sperm.
In this thesis, the biological mechanisms that lead to the formation of ROS/RNS are
reviewed together with the effects of oxidation introduced by reproductive
techniques currently applied in the laboratory or in the field (Chapter 1). A normal
sperm cell can withstand minor levels of peroxidation without appreciable loss of
function. In fact, some molecular substrates must be oxidised in order for a sperm
cell to acquire fertilizing ability and some of the free radicals that are formed act as
signalling molecules essential to capacitation, the acrosome reaction and
penetration of the oolema. Nevertheless, the extent of peroxidation is increased
when sperm cells are submitted to cryopreservation and this excessive
peroxidation of lipids, DNA and proteins is almost certainly detrimental to fertility.
In Chapters 2 and 3, new methods are developed for detecting and localizing (lipid)
peroxidation in viable sperm cells subjected to various treatments e.g. following
freeze/thawing.
Cholesterol is the most abundant molecule in the sperm plasma membrane and
plays an important role in maintaining lipid bilayer stability. In Chapter 4, we
investigated whether cholesterol is a target for oxidative stress, and how oxidised
cholesterol is metabolised within the sperm cell. In addition, we investigated how
different degrees of oxidative stress affect the sperm membrane and the integrity of
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the cytosol, mitochondria and DNA and finally what influence these changes have
on the fertilizing ability and subsequent embryo formation and quality (Chapter 5).
Although sperm may have an intrinsic capacity for withstanding or tolerating certain
levels of oxidative stress it is also possible that the oocyte plays an important role
in repairing oxidative damage in the sperm components introduced during
fertilization. Finally, the results of these studies and their possible implications for
future research are summarized in Chapter 6. In total, we propose that these
results may be useful in human reproductive medicine where sperm of subfertile
men might be used in IVF programmes with improved success following the
addition of specific antioxidant cocktails to prevent oxidation and thereby improve
fertilization rates, embryo harvest, embryo quality and ultimately the likelihood of a
successful pregnancy.
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