London, July 21: Researchers have found a genetic mutation that lies behind one type of male infertility and may have been a cause of unsuccessful In-Vitro Fertilization (IVF) treatments in some couples.
The discovery, made by researchers at Oxford University, Ghent University in Belgium, and the University of Massachusetts in USA and published in the journal Human Reproduction, may provide a new approach to help some couples that have been unsuccessful in IVF treatments, and also could potentially lead to the development of a male contraceptive pill.
The mutation was found in a man known to have a defect in his sperm following initially unsuccessful IVF treatment at a clinic at Ghent University Hospital.
The mutation lies in one specific protein present in sperm called PLC zeta. Recent research, in which the Oxford team also played a significant role, has shown that sperm transfers PLC zeta to the egg on fertilisation. The protein initiates a process called ‘egg activation’ which sets off all the biological processes necessary for development of the embryo.
“An egg cell before fertilisation is in a state of suspended animation. All the biological processes that occur in the growth and development of an embryo are on pause,” explains Dr John Parrington of the Department of Pharmacology at the University of Oxford.
“At the moment of fertilisation, when a sperm fuses with the egg, the egg bursts into life. It’s like a Prince waking Sleeping Beauty,” Parrington said.
The research team took sperm samples from nine men at the same clinic where an IVF procedure known as intracytoplasmic sperm injection, or ICSI, had been unsuccessful. In each of these cases, the eggs had failed to activate.
ISCI involves the direct injection of the sperm into the egg, and is often used in IVF treatment to help ensure fertilisation. However, in two to three per cent of cases where ICSI is used, egg activation doesn’t occur and the fertilised egg doesn’t develop.
ICSI was used in 47 per cent of all IVF treatments in the UK in 2006, or over 20,800 cases. So potentially around 600 couples a year in this country could find that they can’t have children in this way.
The scientists conducted experiments to test how well the protein PLC zeta in these samples was functioning. They found that one man had a mutation in the gene for PLC zeta. The mutation was at a critical point and produced a mutant form of the protein that could no longer trigger egg activation.
This is the first genetic mutation discovered to explain this type of male infertility.
Other samples showed other problems in PLC zeta: like not enough protein, or located in the wrong part of the sperm cell, or a truncated version was produced.
–Agencies