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Last modified: November 06, 2014 09:58:45.
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Breakthrough Discovery on Male infertility Gives Hope to Infertile Couples
2017-03-08

Dr Michail Nomikos, Assistant Professor of Biochemistry at Qatar University College of Medicine (QU-CMED)

 

Infertility is defined as the inability of a sexually active, non-contracepting couple to achieve pregnancy in one year. The World Health Association (WHO) and the American Society of Reproductive Medicine (ASRM) recognize infertility as a disease. It is difficult to address infertility prevalence worldwide, due to problems with diagnosis, management and reporting of infertile individuals and couples. However, in developed countries it is estimated that one in four couples are affected by infertility.

 

Male infertility refers to a male’s inability to cause pregnancy in a fertile female. Historically, people perceived infertility as a “woman’s problem” although male infertility in humans accounts for 40-50% of cases. Approximately 7% of all men are affected by male infertility. Certain lifestyle choices such as smoking tobacco, drinking alcohol, anabolic steroid use, obesity, poor nutrition as well as genetic reasons can affect the reproductive system of a male, causing male infertility. Male infertility is commonly due to deficiencies in the semen. Such deficiencies include azoospermia (sperm are not produced or not present in the semen), oligospermia (only few sperm are produced), sperm motility problems (sperm do not move normally, therefore cannot reach and fertilize the egg), and problems with sperm structure and morphology.

 

Recent clinical studies have reported a number of infertile males with normal sperm parameters (morphology and motility), however their sperm failed to initiate fertilization. Even though their sperm is able to fuse with the egg, after this event nothing happens. It was discovered that sperm from these infertile patients lack a proper functioning version of a sperm protein, called Phospholipase C zeta (PLCz). Sperm PLCz is essential to trigger the first stage of fertilization by initiating a process called ‘egg activation’, which sets off all the biological processes necessary for the development of an embryo. Before fertilization, the egg is in a dormant (“sleeping”) state and all the biological processes required for the growth and development of an embryo are on pause. At the moment of fertilization, when a sperm fuses with the egg, the sperm PLCz protein is delivered into the egg and stimulates all the critical events of egg activation that trigger early embryo development. This sperm protein, which has been called the “spark of life” was discovered in 2002 by Professor F Anthony Lai and his team in Cardiff University (UK).

 

The technical innovation of human in vitro fertilization (IVF) developed by Nobel Prize-winner, Robert Edwards, has helped millions of couples worldwide with infertility problems to achieve successful pregnancies, giving birth to healthy babies. However, there is still a large number of male infertility cases that even the most recently developed IVF techniques are unable to help. Intra-cytoplasmic sperm injection (ICSI), is a powerful IVF technique, which is used extensively by IVF clinics to overcome many conditions of male infertility, such as oligospermia, asthenospermia and teratospermia. In ICSI, sperm is directly injected into the eggs, overcoming any defects related to sperm morphology or motility. However, even ICSI is unable to help cases of infertile males whose sperm fail to fertilize after ICSI, due to defects in the PLCz protein, leading to egg activation failure.

 

My research in collaboration with Professor F Anthony Lai (Cardiff University), aims to address and understand the complex mechanism of how such a small molecule like PLCz, is able to “kick-start” the generation of a new life. The research promises to diagnose and treat cases of male factor infertility where a patient’s sperm is unable to induce egg activation. In 2013, I received the “Fertility and Sterility Investigator Achievement Award” at the annual meeting of the American Society for Reproductive Medicine (ASRM), as the lead and corresponding author of the article “Phospholipase C ζ rescues failed oocyte activation in a prototype of male factor infertility” published in the journal “Fertility and Sterility”. This study discovered that recombinant PLCz protein can successfully replace sperm and trigger development of the egg, up to the blastocyst embryo stage. This research has given hope to many couples facing problems of male infertility. We are currently developing the use of recombinant PLCz protein as a therapeutic agent to treat such cases of male infertility. The research also focuses on the production of PLCz monoclonal antibodies, which could be used for potential clinical diagnosis of such cases of male infertility.

 

As the Nobel Prize-winner Robert Edwards said: “The most important thing in life is to have a child” and to that I add: ‘We will work very hard to make this possible for many couples with such infertility problems.”