A research team led by Professor Kay Ohlendieck from Maynooth University ’s Department of Biology has determined the molecular mechanisms of a particular form of sperm abnormalities called globozoospermia and found that the abnormal morphology of sperm cells plays a crucial role in infertility.
Prior to fertilisation, healthy sperm cells undergo an activation process known as the acrosome reaction, where it releases enzymes and breaks down the outer layer of the egg. In globozoospermia, defective spermatozoa are round-headed and lack the critical acrosome structure so they cannot be properly activated and fail to interact with the female egg cell. This cellular abnormality results in infertility.
The new research approach has used proteomics, the large-scale study of proteins, their structures and functions, to analyse the disorder. The team used scanning and transmission electron microscopy to determine the exact structural abnormalities in infertile sperm cells and has correlated these cell biological features with changes on the molecular level using protein biochemistry and mass spectrometry. The procedure takes all the proteins from the sperm cells, isolates them and carries out an analysis in comparison with normal versions to discover which proteins are different. Over 40 proteins were identified to be abnormally regulated.
This is the first time that a technology driven approach has been taken to abnormal sperm, allowing the team to dive deeper and get a ‘global’ view on how they are affected. The research also identified secondary abnormalities in the sperm. The three year research is a collaborative project between Maynooth University, Aarhus University, Denmark and the University of Bielefeld, Germany. The study has been published in the prestigious biochemical journal ‘Proteomics’ and the research was funded by the Irish Higher Education Authority.
Discussing the research, Professor Kay Ohlendieck, Maynooth University said: “Traditionally research around male infertility has focused on individual proteins or biochemical pathways, but we took a technology-driven approach to studying the abnormalities in sperm. We found that the prevention of the acrosomal reaction in sperm cells appears to prevent fertilization and initiates a cascade of metabolic abnormalities and a cellular stress reaction in defective spermatozoa. Male infertility is responsible for approximately 50% of infertility cases, usually due to deficiencies in semen, so it is crucial that we have a better understanding of this field. If we can better understand the pathology, we might eventually be able to help people with full globozoospermia.”
The research project was carried by Prof Kay Ohlendieck, postgraduate student Ashling Holland, Dr Lisa Staunton and Dr Paul Dowling from Maynooth University, Prof Harald Jockusch and Dr Peter Heimann from the University of Bielefeld, and Prof Thomas Schmitt-John from Aarhus University.