Thesis: Oxidative stress as a mediator of the relationship between age and semen quality: implications for fertility outcomes in the human male
Many countries including Australia, the UK and the USA are witnessing an increasing trend to delay fatherhood to a later age. It is now generally accepted that advanced male age adversely impacts on fertility outcome. However, understanding of the mechanisms behind this age-related decrease is limited. One possible mechanism is via an increase in oxidative stress with age. Oxidative stress is a state where highly reactive molecules known as reactive oxygen species (ROS) overwhelm the body's antioxidant defence mechanisms, causing damage to various cell components. In sperm, oxidative stress causes damage to the cell membrane and DNA, thereby decreasing the quality and fertility potential of the sperm cell. This thesis proposes that in older men (aged >40 years), oxidative stress levels are increased in semen which in turn leads to compromised sperm quality and reduced fertility.
This PhD is composed of three major studies:
1. Examining the effect of male sperm donor age on pregnancy rate in a clinical cohort undergoing donor insemination (DI) treatment
2. Comparing markers of oxidative stress and sperm quality between older and younger men. These include markers of reactive oxygen species (ROS) generation, antioxidant capacity and oxidative damage to the sperm cell.
3. Comparing the effects of cyropreservation (freezing) on markers of oxidative stress and sperm quality between older and younger men.
Why my research is important
There is an increasing trend in developed nations to delay reproduction, such that men and women are reproducing at an older age. Although the age-related decline in female is well-studied, corresponding research in the male has traditionally been lacking.
In addition to decreasing fertility, there are growing concerns that advanced male age may be associated with increased damage to the DNA in sperm, which can lead to chromosomal abnormalities in any resultant embryos.
This becomes particularly important as more couples turn to assisted reproduction for help with conceiving. Although assisted reproductive technology can assist subfertile couples in achieving a pregnancy, it also provides the opportunity to bypass natural barriers.
An understanding of how male age affects sperm quality and ultimately fertility outcome is therefore important within the context of fertility treatment as well as enabling men (and women) to make informed decisions regarding family planning.