13TSB_AgriFood: Optimising the delivery of superior genetics through advanced genomic selection of bovine embryos

Lead Research Organisation: University of Nottingham
Department Name: Sch of Biosciences

Abstract

This proposal is a natural but significant extension of two existing TSB funded projects involving the two collaborating academic institutions (i.e. TS/101069 ['Applying advanced breeding technologies to amplify and distribute bovine genetics to increase production efficiency and sustainability', involving the University of Nottingham], and TS/J003182/1 [Pig IVF and genetics: a route to global sustainability, involving the University of Kent]) to develop advanced breeding technologies in cattle with commercial partners (i.e. Paragon/XLVets, Cogent Breeding Ltd and Illumina Inc) that will allow the marketing of embryos that have undergone a complete genomic evaluation (including sexing) in order to estimate the breeding value of progeny for traits of commercial importance at the earliest possible stage of development.

This project will apply advanced breeding technologies to produce (both in-vivo and in-vitro) pre-implantation bovine embryos from which biopsies will be taken to interrogate their genomic makeup using single nucleotide polymorphism arrays (SNP chips). It is currently possible to screen dairy and beef cattle genomically, but responses to selection are impeded by waiting for the gestation of the calf on which genomic selection is performed. The screening of bovine embryos, however, would optimise the delivery and amplification of superior genetics by advancing the time of selection and reducing "wastage" of unwanted calves of inappropriate sex. This project will, therefore, combine advanced embryo breeding technologies with state-of-the-art genomic screening (so called pre-implantation genetic diagnosis), and karyomapping (combining parental DNA information with the offspring's genomic information to provide more genetic detail). It will develop strategies for: (i) optimal bovine embryo culture using sexed semen, (ii) embryo biopsy in order to extract a small number of blastomeres for genomic analysis, (iii) karyomapping SNP genotype data from Multiple Displacement Amplification products and (iv) ehnancing pregnancy establishment of frozen-thawed embryos. Proof of principle that the new technologies can be used to deliver superior genetics more efficiently to the breeding herd will be confirmed by conducting genomic analyses of calves.

Importantly, this project is geared towards the development and use of a unique and highly marketable product (i.e. genetically evaluated sexed embryos) that will deliver superior genetics to the global market at low cost, and in a high-welfare and bio-secure manner. This will have huge economic benefits for the UK based commercial companies concerned, and for both the dairy and beef sectors of the UK cattle industry; and ensure that the UK remains at the cutting edge of technical innovation retaining its competitive advantage over larger breeding companies currently situated in Europe, North and South America.

Technical Summary

We will apply advanced breeding technologies to produce (both in-vivo and in-vitro) pre-implantation bovine embryos from which biopsies will be taken to interrogate their genomic makeup using single nucleotide polymorphism arrays (SNP chips). It is currently possible to screen dairy and beef cattle genomically, but responses to selection are impeded by waiting for the gestation of the calf on which genomic selection is performed. The screening of bovine embryos, however, would optimise the delivery and amplification of superior genetics by advancing the time of selection and reducing "wastage" of unwanted calves of inappropriate sex. This project will, therefore, combine advanced embryo breeding technologies with state-of-the-art genomic screening (so called pre-implantation genetic diagnosis), and karyomapping (combining parental DNA information with the offspring's genomic information to provide more genetic detail). It will develop strategies for: (i) optimal bovine embryo culture using sexed semen, (ii) embryo biopsy in order to extract a small number of blastomeres for genomic analysis, (iii) karyomapping SNP genotype data from Multiple Displacement Amplification products and (iv) ehnancing pregnancy establishment of frozen-thawed embryos. Proof of principle that the new technologies can be used to deliver superior genetics more efficiently to the breeding herd will be confirmed by conducting genomic analyses of calves.

Importantly, this project is geared towards the development and use of a unique and highly marketable product (i.e. genetically evaluated sexed embryos) that will deliver superior genetics to the global market at low cost, and in a high-welfare and bio-secure manner. This will have huge economic benefits for the UK based commercial companies concerned, and for both the dairy and beef sectors of the UK cattle industry; and ensure that the UK remains at the cutting edge of technical innovation retaining its international competitive advantage.

Planned Impact

This project is geared towards the use of a unique and highly desirable saleable product; that is the marketing of embryos that have undergone a complete genomic evaluation (including sexing) in order to estimate the breeding value of progeny for traits of commercial importance at the earliest possible stage of development. This new 'product' (approach) has the benefit of significantly reducing the generation interval (by at least 9 months). The additional introduction of sexed semen/embryos has the advantage of increasing the number of embryos/progeny of the desirable sex for genomic analysis, and this facilitates greater selection intensity. Collectively these approaches will increase response to selection for desirable traits associated with yield, fertility and animal health.

Such an approach will have huge economic benefits for both the dairy and beef sectors of the UK cattle industry, and ensure that the UK remains at the cutting edge of technical innovation retaining its competitive advantage over larger breeding companies currently situated in Europe, North and South America. It also offers important environmental, ethical, biosecurity and animal welfare benefits. The judicious selection of calf sex avoids the production of 'unwanted' greenhouse-gas emitting ruminant offspring (which may otherwise need to be destroyed), and facilitates increased selection intensity for desirable traits that may include increased disease resistance (e.g. bovine tuberculosis). Developmentally competent and genetically evaluated sexed embryos are also a highly marketable commodity that can deliver superior genetics to the global market at low cost, and in a high-welfare and bio-secure manner.

The primary route to market will exploit an embryo transfer service offered by Activf-ET (established as part of TSB Project 101069, 'Applying Advanced Breeding Technologies to Amplify and Distribute Bovine Genetics to Increase Production Efficiency and Sustainability' of which the University of Nottingham is a partner), in collaboration with Cogent Breeding Ltd, who are also partners in this TSB project, and in the current application. A new partner to our consortium is Professor Darren Griffin (University of Kent), who has experience with a separate TSB project (TS/J003182/1: Pig IVF and genetics: a route to global sustainability). In the current proposal sexed and genetically evaluated embryos would not only be created for the domestic UK market, but would also become available for export to new and rapidly expanding markets in China and India, as well as to more established markets across Europe and North America. This is readily achievable in parallel with Cogent's established frozen semen worldwide distribution (spanning 35 countries).

A significant element of training exists in the current proposal, not simply among the various partners most closely associated with this bid, but also to the extensive network of XLVets (based in 51 geographically distributed practices throughout the UK). Many of these practices will be trained in techniques of oocyte retrieval from donor cows (OPU) and embryo transfer (ET) into recipient cows. There are also aspects of oocyte donor and embryo recipient management that need to be extended to participating farmers. This will be achieved through the publication of technical literature and via a series of stake-holder meetings during the 3 years of this project, during which advice and guidance would be offered on general cow management and health, but more specifically on aspects such as oestrus synchronisation and heat detection, and strategies to enhance early embryo survival following transfer. The Kent group will take the lead with a significant training element. Recently they launched an MSc course in Reproductive Medicine that contains a 'hands on' one week practical course. This module is being developed for individuals wishing to enter both clinical and animal IVF.
 
Description For the work undertaken at Nottingham we used sexed semen from a variety of sources including Semex and, latterly, Ultra-sexed semen (Sexing Technologies) was used. Ongoing issues of semen contamination meant that we did not use Cogent semen. Not certain if the reduction in blastocyst yields (i.e. blastocysts of matured or cleaved) in 2015 was associated with the increased yield of oocytes (i.e. more poorer-quality oocytes selected for IVP. Could simply be a donor-cow effect. However, blastocysts per OPU of 3 when with sexed semen is exceptionally good.


Year 1 Year 2
Unsorted Sexed Unsorted Sexed
Number of OPUs 67 15 38 39
Oocytes/OPU 13.4 14.7 19.8 19
Oocytes matured/OPU 10.7 9 13 15.4
Cleavage 59% 50% 51% 66%
Cleavage index 83% 74% 72% 72%
Number of blastocysts 218 18 86 116
Blastocyst rate/cleaved 52% 26% 34% 29%
Blastocyst rate/oocytes 30% 13% 17% 19%
Blastocysts/OPU 3.3 1.2 2.3 3.0
Fresh transfers 36 0 0 0

A number of independent factors at the beginning of this project conspired to impede initial progress. These included the closure of our local abattoir (Pickstock Ashby Ltd) and primary source of bovine ovaries in January 2014, followed by extended sick leave of a key technician whose role was to collect bovine ovaries. Collections resumed in March 2014 with the majority of ovaries coming from the new Pickstock plant in Telford (2 h journey-time each way). Negotiations with Semex/Boviteq had begun by this stage and formal meetings held in June 2014 with a view to us moving over to their system for egg recovery and embryo culture during 2014. However, protracted negotiations meant that this didn't happen until later in 2015. A further issue during 2014 related to contaminated sexed semen from Cogent Breeding Ltd which prevented us from making headway with this element of the project. It also tied up a lot of lab time trouble shooting the problem. Cogent subsequently withdrew from the project later in 2014. It also transpired that the fixed laser (Hamilton-Thorne, X-Y Clone) and micro-manipulation rig available at Nottingham was technically more demanding to use relative to more contemporary systems. Following discussions with Research Instruments Ltd, Falmouth, UK we have installed a new system (on loan) on 17th December 2015. A similar system is to be installed in the lab at Newbiggin on 18th December. This will facilitate training and exchange of protocols between the two labs. During the past two years the Nottingham lab has continued to generate commercial IVP embryos from oocytes collected by the Cheshire team as part of TSB-Agrifood (101069).

WP2A.Develop an optimum strategy for production of biopsied and sexed embryos: post-thaw viability.

Start date: 01/12/2013
Objective 1: Determine the best stage of pre-hatching embryo development for biopsy.
Traditionally, most bovine embryo biopsies are performed using a microblade in Day 7 blastocysts. This is recognised as being traumatic to the blastocyst, especially if vitrification and freezing are necessary post biopsy. Laser-assisted biopsies by micro-manipulation can, to an extent, overcome this limitation, but remain technically challenging. The biopsy of early, cleavage-stage embryos that have not yet formed tight junctions between blastomeres offers the prospect of a technically less demanding, and biologically less traumatic, means of biopsy.

Day 7 biopsies
Using the micromanipulation rig and laser system currently available at Nottingham, early attempts with Day 7 expanded blastocysts proved difficult, embryos tended to collapse around the biopsy pipette making each biopsy virtually impossible. Embryos that were less advanced (e.g. mid blastocysts) proved more successful. Their zonas were thicker and so did not split when aspirating trophectoderm cells into the pipette.

We found that punching a hole into the zona pellucida on Day 4, 5 or 6 was more successful. Subsequent Day 7 blastocysts herniated and biopsies were completed without the remaining part of the embryo leaving the zona. One potential problem with this approach is that the embryo could hatch ICM first. Intuitively, it may be best not biopsy polar trophectoderm cells, as there is a higher probability of recovering ICM cells. Our initial studies, however, suggest that this may too critical.
In total we have undertaken 7 such experiments to assess the efficacy of blastocyst biopsies, involving 707 oocytes that went into maturation, 478 cleaved (68%) and 95 blastocysts were produced (20%). Most of these were used to establish the optimal parameters for biopsy. Of the 23 that were successfully biopsied in these experiments 16 survived and re-expanded (70%).

Most recent attempts have proved more successful. In a recent experiment, twenty two Day 7 blastocysts were produced and 14 were deemed suitable for biopsy. Biopsied embryos invariably collapsed and were returned to culture to assess re-expansion, and survival. Biopsies were frozen in individual tubes and are available for studies at Kent. Of the 14 blastocysts, 12 (86%) re-expanded and began hatching or hatched. We recovered a variable but appropriate number of cells by this approach - typically 10 to 20.

Recommended method for the project based on the current system at Nottingham is to punch a hole in the zona pellucida at the early morula stage (Day 4), and then undertake biopsies in Day 7 expanding blastocysts. By this stage the expanding blastocyst is starting to herniate through the incision made 3 days earlier, and this facilitates biopsy. This approach requires regular monitoring. The new rig and laser systems at Nottingham and Newbiggins may facilitate an alternative and possibly easier approach. We also feel that there is merit in considering earlier stages of development for blastomere biopsy, but that this requires further development. We plan to undertake these experiments and to compare with the efficiency of blastocyst biopsy during 2016. For the time being, however, we advocate blastocyst biopsies as described above.

Early cleavage stages
Blastomere biopsy of early cleavage-stage embryos (8 - 16 cells) is technically less challenging. Blastomeres have yet to form tight junctions and so are easier to excise. This approach also gives the embryo more time to recover. One disadvantage with this approach is that cell numbers recovered are low (we electively recover 2 blastomeres from > 8 cell embryos), and therefore potentially limiting for subsequent genomic evaluation using existing approaches. Furthermore, 2 cells from an 8 to 16 embryo are proportionally greater (but only slightly) than 10 to 20 cells from a 100 to 140 cell blastocyst. Also, some embryos are biopsied that are not likely to push onto the blastocysts stage.

Initial attempts to proliferate blastomeres were not successful. These experiments used Day 2 to Day 4 embryos where the zona was removed with pronase and blastomeres separated by gentle pipetting. These were then cultured in groups (2 to 8 cells) in 96 well plates. Growing on inactivated STO cells was also not successful initially but proved so subsequently. However, this was approach not pursued since this could potentially complicate subsequent analysis carried out by Kent (i.e. amplify mouse DNA along with bovine DNA). However, incubating blastomeres in a Well-of-the-Well (WOW) system (typically in 5 to 10 µl drops under oil) proved to be the most successful.

In one experiment, twenty eight Day 2 embryos (all 8 cells) were dissociated, split into 2 cell (n = 10) or 4 cell (n = 18) groups and cultured for 5 days in the WOW system. Of the group of 18 embryos (4 cells per well), 4 gave rise to two blastocysts each (total of 8 blastocysts), and one gave rise to one blastocyst. Of the group of 10 embryos (2 cells per well), 2 produced double blastocysts each and one produced three blastocysts. Overall eight 8-cell embryos produced at least 1 blastocyst (29%) and 16 blastocysts were produced overall (i.e. 16 blastocysts from twenty-eight 2-cell embryos - 57% blastocyst yield).

The point of these experiments was not to demonstrate that we can bisect cleavage stage embryos to increase the yield of blastocysts, but to demonstrate that blastomeres in a WOW system can proliferate and produce enough cells (i.e. greater than 10 cells) for genomic evaluation. These latter experiments indicate that we can achieve this objective, although there is scope for further optimisation.

Objective 2. Determine minimum number of blastomeres required to achieve the highest possible call rates

To achieve this objective we have produced and sent blastomeres and whole embryos to the University of Kent for DNA extraction, amplification and subsequent analyses. Most of the embryos produced in Table 3 were sent to Kent along with the corresponding ovary samples and sperm.

Objective 3. Determine most efficient strategy to generate viable biopsied and sexed post-thaw embryos

This objective sought to assess post-thaw viability of biopsied embryos generated using (a) unsorted (b) sex-sorted and (c) reverse-sorted sexed semen supplied by Cogent Breeding Ltd. As discussed earlier in this report, issues surrounding contaminated semen from this partner and their subsequent exit from the program meant that this aspect of the project could not be taken forward. Current and prospective market conditions suggest that demand for reverse-sorted sexed semen may be limited, and so it is questionable as to whether this would be a sensible strategy to pursue.

Update on genomic evaluations (March 2017)
Karyomapping was originally developed as a universal means of detecting monogenic and chromosome disorders simultaneously in human IVF embryo using SNP chips. The major non-human applications of SNP chips however lie in animal breeding. Traditional practice in the UK beef and dairy breeding industry involves the selection of dam (female) and sire (male) lines based on phenotypic progeny testing of live born animals. Genomic estimated breeding values (EBVs) are increasingly identified through SNP chip interrogation strategies, especially for sires.

Combining SNP chip genotyping with IVP technology (generating EBVs from embryos rather than live-born animals) is a much-needed advance as it significantly increases selection intensity whilst shortening the generation interval, thereby expediting the introduction of new genetics to the supply chain. To this end, we have adapted PGD technology involving IVP of cattle embryos, blastocyst biopsy, whole genome amplification then interrogation of SNP ships for the screening of cattle embryos. Simultaneous genotyping and aneuploidy screening is possible using karyomapping. This approach complements traditional morphology screening to enable the selection of embryos with the best chance of survival to term, and ensures that resulting calves are proven carriers of desirable traits (e.g. those associated with health, welfare and productivity). Moreover, Karyomapping effectively acts as a genetic fingerprint to confirm the diagnosis of the embryo by matching it with that of the live born calf.

At time of writing, 77 embryos have been genotyped in this way and we have made the first preliminary estimates of aneuploidy rates and high-resolution recombination patterns in cattle. A total of 16 embryo transfers have been made, of which 6 led to pregnancies. 1 of these is ongoing, 1 aborted at 4 months. 4 were born but 1 died soon after birth of a post-natal infection. More transfers and pregnancies are imminent and we continue to improve protocols. In the most recent run, following transfer of 2 chromosomally normal blastocysts, 2 live births of Holstein calves ensued.

Follow-up studies have been and are being undertaken in collaboration with our industry partners as part of a subsquent Innovate UK funded study, a KTP and a BBSRC-LINK grant, as well as two studentships. Some of this work is investigating pregnancy outcomes following embryo transfer, up-scaling embryo biopsy techniques to facilitate high-throughput geneomic testing and using aneuploidy screening as a means to imnprove pregnancy outcomes. Findings from these studies will be made available over the next two years.
Exploitation Route This project is directly related/supported by industry through Innovate UK - our industry partners are being trained in technqiues and are applying techniques to commercial embryo production. As stated above, three subsequent awards are allowing us to take forward specific aspects (i) High-throughput embryo biopsies, (ii) further refinements to oocyte collection and culture, and (iii) aneuplidy screening to enhance pregnancy outcomes folllowing embryo transfer.
Sectors Agriculture, Food and Drink

URL http://www.activf-et.com/
 
Description Yes. Methods for embryo culture and biopsy have been adopted by the industry partners. A number of pregnancies have already been established. The project still has 10 months to run. Karyomapping has been applied to assist in genomic evaluation of Day 7 cattle embryos successfully for the first time, with live offspring born Following on from the end of the project work Activf-ET Ltd was launched to deliver the IVF and Biopsy services developed during the course of the project. • Activf-ET has a main board of directors (5 people) with representation from each of the shareholders who meet quarterly. A business manager is employed 2 days per week, an accountant and MD each 2 day per week. • 6 established OPU teams over the UK employing 11 Vets, 7 Technicians • 1 IVF lab (at Paragon) with 2 full time employees • 6 Transfer teams over UK employing 6 vets and 6 technicians Technical support • Weekly Stats report from database to monitor team performance • Paragon (PVG) OPU team lead - deliver ongoing OPU team training, regular QC visits/team training events • Fortnightly Skype calls for technical exchange with Canadian partners who supply the media, to build on current expertise. OPU Stats: No of OPU's %age cleaved Embryos per OPU Transfers Producing embs During project (3 years): 1848 40.49 1.34 970 9 months since project end: 286 42.74 2.49 438 PVG team (9mths) 157 44.46 2.6 318 PVG Jan 2018 39 53.77 4.02 2 Performance and output, building rapidly as shown above Marketing • Marketing the business alongside whole herd genomic testing to select potential donors which should drive the business and shift the emphasis towards pre-implantation genomic evaluation by biopsy and SNP chip analysis. • Initiatives being launched alongside partners to create momentum: Voucher scheme for subsidised collections Funding for 3 monitor farms for whole herd evaluation and IVF on highest ranking donors with subsequent data collection to evaluate the financial benefits. • Exploring European opportunities and drawing up bilateral agreements with European partners • Natural business growth due to good results and word of mouth Academic • DVM Thesis submitted February 2018. To be defended May 2018-02-22 • Abstract for short presentation accepted for 2018 World Buiatrics Congress in Sapporo "Establishing a robust ovum pick up (OPU) and in vitro embryo production (IVP) system for use in UK cattle breeding" • Paper presented at Semex Dairy Conference January 2018 - "Advances in Bovine Advanced Breeding" Success completion of this project has led to the award of three new research projects (BBSRC-LIN, commenced June 2018; Innovate UK KTP, commenced March 2019; Innovate UK, commenced March 2019; PhD studentship awarded by Turkish government. These projects seek to further develop and refine methods for in vitro production of cattle embryos for genomic selection and improvements in animal breeding.
First Year Of Impact 2017
Sector Agriculture, Food and Drink
Impact Types Economic

 
Description BBSRC response mode (LINK)
Amount £2,577,050 (GBP)
Funding ID BB/R007985/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 04/2018 
End 03/2021
 
Description Improving bovine in vitro embryo production through follicular flushing and next generation embryo culture
Amount £867,177 (GBP)
Funding ID 105142 
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 03/2019 
End 02/2022
 
Description Innovate KTP - High throughput laser assisted biopsy in cattle embryos
Amount £274,046 (GBP)
Funding ID KTP11542 
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 03/2019 
End 02/2022
 
Description Introducing karyomapping to the cattle breeding industry: use of a comprehensive preimplantation genetic test to optimise the delivery of superior genetics 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk on research findings from award given at European Society for Domestic Animal Reproduction - attended by scientists, practitioners and industry
Year(s) Of Engagement Activity 2017
URL http://www.esdar.org/esdar-conference-2017/prog-2017-gb.html
 
Description Boviteq Veterinary Practitioner Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Meeting held in Minneapolis USA for veterinary practitioners from UK, USA and Canada. Concerned recent technical and scientific advancements arising from study and how these could be put into commercial practice.
Year(s) Of Engagement Activity 2016
 
Description British Cattle Veterinary Association 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Conference of the British Cattle Veterinary Association - outreach activity to provide update on research progress to date and to engage with clinicians in the hope of indetifying participating farms for final phase of ongaining study.
Year(s) Of Engagement Activity 2015
 
Description Dairy Science Forum - May 2015 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Agricultural industry leaders, veterinary practitioners and leading academics attended this two day meeting which involved lectures and pratical demonstrations of egg recovery, embryo culture and biopsy - techniques under development and whcih are currently being implemented into commercial practice.
Year(s) Of Engagement Activity 2015
URL http://www.dairyscienceforum.org/
 
Description Dairy Science Forum - November 2013 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact A full day meeting with leading scientists, industry leaders and policy makers (including Defra, TSB) where the topic was focused on current research (BBSRC/TSB), recent developments and use of advanced breeding technologies in dairy cattle in the UK. Lengthy discussions followed short presentations and a tour of our experimental facilities.


I was invited to become a member of the Dairy Science Forum, which is a 'think-tank' of leading scientists and members of industry.
Year(s) Of Engagement Activity 2013
 
Description ESHRE Campus Event - Embryo innovation: the legacy of the past and visions of the future 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact First of two talks at "Embryo innovation: the legacy of the past and visions of the future" ESHRE Campus symposium organised by the Special Interest Group Embryology
Bratislava, Slovakia. Aimed primarily at early career clinicians, nurses and other health-care professionals, the talk covered aspects of parental nutrition during the periconceptional period with emphasis on one carbon metabolism, and long-term epigenetic consequences for offspring health. Lot's of debate and discussion regarding implications on parental diet and fortification of flour with B vitamins.
Year(s) Of Engagement Activity 2019
URL https://www.eshre.eu/Eshre/Login.aspx?returnUrl=%2FSpecialty-groups%2FSpecial-Interest-Groups%2FEmbr...
 
Description ESHRE Campus Event - Embryo innovation: the legacy of the past and visions of the future - Second of two talks 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Second of two talks - this one focusing on safety of IVF in relation to child health. Heavy emphasis once again on one carbon metabolism, as it is affected by ART procedures, and embryo culture media composition. Much debate concerning implications for child health as human IVF labs now encountering problems observed in animal studies stretching back 20-30 years.
Year(s) Of Engagement Activity 2019
URL https://www.eshre.eu/Eshre/Login.aspx?returnUrl=%2FSpecialty-groups%2FSpecial-Interest-Groups%2FEmbr...
 
Description Innovation and impact show case - University of Nottingham 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Intended purpose to showcase collaborative research with industry. Outcomes led to the application and successful award of an Innovate UK KTP and Innovate UK grant to extend investigations towards the end of 2018
Year(s) Of Engagement Activity 2018
URL https://www.nottingham.ac.uk/home/featureevents/2018/research-in-action-innovation-and-impact-showca...
 
Description Nottingham Cattle Fertility Conference 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact An annual meeting held at Nottingham University each year and organised by the PI. In June 2013 and 2014, topics presented and discussed at this meeting releated directly to Advanced breeding technologies in cattle - where the Project Leader and MD of one of the industry partners gave an address in 2013, and one of the Technical Directors addressed the meeting in 2014.

Additional veterinary practices have either enquired about or will join our growing partnership
Year(s) Of Engagement Activity 2013,2014
URL http://www.nottingham.ac.uk/conference/fac-sci/cattle-fertility/index.aspx
 
Description Parental diet and ART: Consequences for epigenetic programming of life-time development 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Extended seminar and discussion with staff and students at the University of Bradford. Discussions around future collaboratoration and student support.
Year(s) Of Engagement Activity 2021
 
Description Recent advances in reproductive molecular technologies in advanced cattle breeding 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Course for veterinary practitioners engaged in cattle breeding hosted by the University of Liverpool. Part of CPD and training in advanced cattle breeding.
Year(s) Of Engagement Activity 2020
URL https://www.liverpool.ac.uk/study/postgraduate-taught/taught/dbr-bovine-reproduction/overview/
 
Description Sperm preparation for bovine intracytoplasmic sperm injection (ICSI) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk given at Fertility 2018 - joint meeting of UK fertility society bringing together 959 international scientists, practitioners, clinical embryologists, health-care professionals and students. Judith Gomez-Martinez (3rd year PhD student; supported by the University of Nottingham) won the Professor Iwan Lewis-Jones 'Young Scientist Prize' for best oral scientific presentation in Andrology (jointly awarded by the British Fertility Society and British Andrology Society).
Year(s) Of Engagement Activity 2018
URL https://fertilityconference.org/programme/
 
Description Talks at Fertility 2020: an international meeting involving basic scientists, clinicians, nurses and health care professionals - first of two 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Over 1000 delegates attended this event in Edinburgh. Talk initiated questions and discussion - increased awareness of importance of parental diet and nutrition during the periconceptional period. Of interest to IVF clinics and health-care professionals more generally.
Year(s) Of Engagement Activity 2020
URL https://fertilityconference.org/
 
Description Talks at Fertility 2020: an international meeting involving basic scientists, clinicians, nurses and health care professionals - second of two 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Second on two talks - this one focused on efficiency and safety of ART with strong focus on aneuploidy. Generated much debate afterwards - safety of human ART and value of aneuploidy screening. Also - much interest from livestock breeding sector.
Year(s) Of Engagement Activity 2020
URL https://fertilityconference.org/
 
Description Timing of in vitro fertilisation determines embryo development from bovine oocytes treated with the proteasome inhibitor MG132 during in vitro maturation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster presentation and discussion of data relating to PhD linked to the research award.
Year(s) Of Engagement Activity 2018
URL http://edition.pagesuite-professional.co.uk/html5/reader/production/default.aspx?pubname=&pubid=417c...