Understanding and assessing impact of hyaluronidases in supporting preimplantation embryo development

Lead Research Organisation: Royal Veterinary College
Department Name: Comparative Biomedical Sciences CBS


Low fertility is a problem in domestic animals and human, impose major economic loss for farmers and social discomfort and costs to couples and expenses to the NHS. To date, efficiency of embryos production in the lab is much less than of those grown in the body, indicating a need for further research to improve formulation of embryo culture media. With BBSRC support, we have identified an enzyme (Hyal-2) which chops embryos' and oviductal hyaluronan (HA) to improve embryo development and quality when added to cow or sheep embryo culture or infused into the sheep oviduct. Similar enzymes are released by sperm at fertilisation in the oviduct. These enzymes could improve efficiency of embryo culture media, but before commercialization, further knowledge of their actions is needed. Our study will test Hyals and HA on sheep embryos in our laboratory. We will place treated embryos in ewes to measure pregnancy rates. We will also begin studies on human embryos, with ethical approval.


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Description Our data showed that hyal2 is produced by both human and sheep embryos and is detectable in the spent culture media prompting the possibility of its use as a non-invasive biomarker for prediction of embryo quality.
In addition, we have found that hyal2 treated embryos result in higher pregnancy rate after transfer to recipient ewes.
Exploitation Route These data is attracting interest from a commercial producer of culture media for human assisted reproduction.
Sectors Agriculture, Food and Drink,Healthcare,Pharmaceuticals and Medical Biotechnology

Description The beneficial effects of small-size HA in enhancing embryos development and quality has been embraced by Origio a major producer of culture media for human assisted reproduction. They are now producing some culture media containing hyaluronan.
First Year Of Impact 2017
Sector Healthcare,Manufacturing, including Industrial Biotechology
Impact Types Economic

Title Improving success of IVF 
Description The data from my BBSRC Follow-on Fund grand has revealed that the elements from hyaluronan system can be used to improve embryo development rate resulting in improved pregnancy rate in sheep. 
Type Of Material Biological samples 
Provided To Others? No  
Impact Human fertility treatment and animal IVF will benefit from this technology. Interests has been expressed from commercial companies involved in human and animals assisted reproduction technology. 
Description Hyaluronidase and biomarker 
Organisation Covidien
Department Research and Development
Country United States 
Sector Private 
PI Contribution In partnership with Origio, we conducted research on development of biomarker predictor of embryo quality
Collaborator Contribution Origio paid 25000 Euros to match the equal fund by the RVC. This fund provided budget for employing a post doc for 9 months plus the research consumables.
Impact We created more evidence to indicate that human embryos produce hyal2 which is measurable in the spent culture media. Its level has high correlation with embryo quality and pregnancy outcome.
Start Year 2016
Description University of Warwick 
Organisation University of Warwick
Country United Kingdom 
Sector Academic/University 
PI Contribution I discussed the results of my research about involvement of hyaluronan system in embryo implantation with Professor Jan Brosens. He is one of the leading researchers in human fertility focusing on regulation of embryo implantation in the uterus and the role of leukocytes. This meeting was mediated through my research collaborator Professor Geraldine Hartshorne. Subsequently, I sent a number of reagents to test the effect on human uterine cells.
Collaborator Contribution Professors Jan Brosens and Geraldine Hartshorne recruited a MSc student to carry out the experiments. The results are highly promising and has led to new discoveries which is due to be submitted as a manuscript.
Impact I expect submission of the first manuscript with the next few months.
Start Year 2019
Title P60757GB 
Description 1. Use of very low molecular weight hyaluronan fragments as supplement for human and animals embryo culture 2. Use of hyals as supplement for human and animals embryo culture 3. Hyal-2 as a biomarker of embryo quality and predictor of pregnancy outcome after embryo transfer 4. Inhibition of hyaluronan synthesis in the uterus enhances embryo attachment and pregnancy rate 
IP Reference  
Protection Patent granted
Year Protection Granted 2016
Licensed No
Impact The Notable impact will be in human assisted reproductive technology, animal embryo transfer including endanger animal species