Infertility has become a critical worldwide health burden, with 1 in 6 couples currently seeking the help of assisted reproductive technology (ART) in Australia. However, the consequences of infertility go beyond childlessness with the failure to conceive now documented as a leading cause of marital violence, psychological abuse, and economic instability. With an estimated 80 million individuals experiencing the weight of this problem globally there is an overwhelming need for novel preventative strategies that will safeguard the fertility of current and future generations.

At least 50% of infertile cases in Australia involve a male factor, making defective sperm function the largest single, defined cause of human infertility. Unfortunately, due to a severe lack of mechanistic knowledge surrounding sperm function, there are few molecular tools available for the accurate diagnosis of male infertility and no curative treatments. This is particularly concerning as there is compelling evidence that poor sperm quality is predictive of major systemic diseases such as cardiovascular disease, diabetes, and cancer.  In this light, there has never been a more pressing need to determine the underlying cause of defective sperm function. Although 25-40% of male infertility cases are idiopathic, it is now well established that up to 80% of these cases are underpinned by cellular oxidative stress. Such stress can arise through diverse environmental, endocrine or intrinsic sources, but these factors all lead to a synonymous pathway that drives spermatozoa towards dysfunction, decline and cell death. Our work examining oxidative stress in the male germline has led to the important discovery of a new enzyme responsible for its catalysis termed 15-arachidonate lipoxygenase (ALOX15). This discovery gives rise to exciting new avenues for the therapeutic intervention of oxidative stress-mediated infertility.
Hypothesis: The novel idea that underpins this project is that ALOX15 is a key mediator of oxidative stress in the male germline. On the basis of our extensive pilot data, we propose that the inhibition of ALOX15 will reduce oxidative stress and improve human sperm function. This project will provide new therapeutic strategies to mitigate the growing health burden of infertility.

Specific aims: 

  1. To explore the role of ALOX15 in the onset of oxidative stress and germ cell death
  2. To evaluate ALOX15 inhibition as a strategy to improve human sperm function

Dr Elizabeth Bromfield, Prof Brett Nixon

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