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The International Journal of Molecular Science publishes IVF-Life’s Latest Research on Phospholipase C Zeta in Spermatozoa, Key in Tackling Male Infertility

IVF-Life professionals, in pursuit of representing another milestone in their constant commitment to science and development, have presented their latest study in the International Journal of Molecular Sciences: Phospholipase C Zeta in Human Spermatozoa: A Systematic Review on Current Development and Clinical Application. Through this publication that joins the scientific literature, the authors Alessandra Parrella (embryologist), Llanos Medrano, IVF-Life Alicante Laboratory Director, Jon Aizpurua, president of the group, and María José Gómez-Torres, head of the Human Fertility Department at the Universidad de Alicante, open up a new research avenue to identify and address male infertility.

What is the Origin of the Research?

As is well known, fertilisation is what happens when the sperm fuses with the egg, and it is important to note that the release of calcium from the endoplasmic reticulum of the latter is crucial for this process to be successful. This step triggers a series of calcium ion (Ca2+) oscillations, leading to what is known as egg activation.

In this context, we need to understand that a sperm-specific factor, phospholipase C zeta (PLCζ), is the one responsible for egg activation. The latest IVF-Life study explains that men undergoing intracytoplasmic sperm injection (ICSI) who provide sperm lacking PLCζ are unable to generate Ca2+ oscillations, making fertilisation impossible. When we identify patients with reduced or absent ability to activate eggs, a technique called assisted oocyte activation (AOA) is used, which can help achieve successful ICSI results and shorten the treatment times needed to achieve pregnancy. 

With their latest promising research, the goal of our professionals has been to study and review in depth all the available literature regarding PLCζ, also discussing new genetic mutations associated with its deterioration. Similarly, the research has provided insight into the prospects of AOA, revealing innovative and less invasive methods to diagnose and treat these cases. 

New Perspectives for the Diagnosis of Phospholipase C Zeta (PLCζ) deficiency

As outlined from Phospholipase C Zeta in Human Spermatozoa: A Systematic Review on Current Development and Clinical Application, certain patterns of PLCζ expression and localisation in human spermatozoa need to be taken into account and identified, as they are directly linked to male infertility. This, for instance, is the case for patients who show a decrease in PLCζ expression, with their fertilisation rates being lower. An example confirming this is the low expression and mutation of PLCZ1 in patients with complete globozoospermia – a rare condition characterised by sperm cells with no acrosome head, which is a crucial part for fertilisation to take place.

Another aspect studied in IVF-Life’s paper is the debate surrounding sperm selection techniques that increase the percentage of sperm expressing PLCζ. While density gradient centrifugation (DGC) does not meet the aforementioned target, as it removes sperm with a low capacity to induce egg activation from the equation, there are other procedures that appear to be able to do so.

On the one hand, carrying out microfluidic-based sperm sorting effectively isolates spermatozoa with high levels of PLCZ1 expression, whereas the Zeta method enhances the intensity of PLCζ expression in the selected spermatozoa (instead of increasing their number, as occurs with DGC).  Thus, it is suggested that combining DGC and the Zeta method will likely result in a good selection of spermatozoa with oocyte activation capacity. There are further studies mentioned which have shown that another technique, the motile sperm organelle morphology examination (MSOME), can be beneficial for selecting spermatozoa that exhibit acrosomal cap morphology and express PLCζ in their head regions. 

What Courses of Action are Proposed for Phospholipase C Zeta Deficiency?

Although AOA is the procedure of choice for PLCζ deficiency or absence, experts are in the process of finding alternative treatments with superior efficacy, focusing on triggering calcium oscillations in oocytes, by, for example, microinjecting PLCζ mRNA or recombinant protein into the oocytes. However, it should be noted that there has not yet been enough research to approve the use of this compound and to detect possible adverse effects.

For some time now, the scientific community has been looking into the importance of the role of PLCζ in oocyte activation, developing tools to identify patients who tend to show fertilisation failure. This, in clinical practice, allows us specialists in reproductive medicine to provide a specific treatment in each and every case in our In vitro fertilisation treatments, focused on successful fertilisation, adequate embryo development and, of course, the early achievement of pregnancy.