Recombinant protein may treat male factor fertility

By Liam Davenport, medwireNews Reporter

Male factor infertility resulting in failed oocyte activation from dysfunctional sperm phospholipase C-zeta (PLCζ) may be remedied through the use of a recombinant form of the protein, leading to efficient blastocyst formation, say scientists.

Lead researcher Tony Lai, from Cardiff University School of Medicine in the UK, commented in an associated press release: "We know that some men are infertile because their sperm fail to activate eggs. Even though their sperm fuses with the egg, nothing happens. These sperm may lack a proper functioning version of PLCζ, which is essential to trigger the next stage in becoming pregnant.

"What's important from our research is that we have used human sperm PLCζ to obtain the positive results that we had previously observed only in experiments with mice."

He added: "Whilst this was a lab experiment and our method could not be used in a fertility clinic in exactly the same way, there is potential to translate this advance into humans. In the future, we could produce the human PLCζ protein and use it to stimulate egg activation in a completely natural way."

The team conducted a series of experiments to measure the efficacy of mutant and wild-type PLCζ-mediated enzyme activity, oocyte calcium oscillations, activation, and early embryo development in donated unfertilized human oocytes from follicle reduction.

As reported in Fertility and Sterility, microinjection of recombinant wild-type human PLCζ into mouse and human eggs revealed a potent ability to induce cytoplasmic calcium oscillations. It initiated highly efficient early embryo development, from pronuclei formation up to the multicellular blastocyst stage, which occurred in 50% of microinjected eggs.

By contrast, microinjection of one mutant form of PLCζ entirely failed to cause any calcium oscillations in mouse eggs, while another mutant was associated with a significant delay in the initiation of cytoplasmic calcium oscillation, and neither of these mutant forms of the protein was associated with the activation of embryo development.

Indeed, the enzyme activity of one mutant form of PLCζ was just 24% of that seen in the wild-type protein, while the other mutant had no enzymic activity, note the researchers.

Injecting purified recombinant, human wild-type PLCζ after injection of a mutant form of the protein immediately led to highly effective induction of normal calcium oscillations and successful embryo development up to the multicellular blastocyst stage, with an efficacy approaching 60%, the team concludes.

Licensed from medwireNews with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.