Good fertility performance is the cornerstone of a profitable and sustainable livestock enterprise. In the international dairy and beef herd, optimum performance is achieved by maintaining a calving interval (CI) of 365 days. Every day CI increases \>365 days is estimated to directly cost the farmer ~GBP2.07/CAN$3.54/cow, or more for high yielding dairy cows. Fertility drives productivity and in turn the mitigation of greenhouse gas (GHG) emissions through reduced waste and optimising unproductive replacement youngstock inventories. This project will research and develop a number of innovative new technologies and establish national level referral facilities for quality assurance and improvement of bovine germplasm, as an integrated bilateral approach. The outputs of the project will transform genetic progress, through adoption of precision technologies, diagnostics, advanced breeding and big data, leading to more sustainable livestock food production and export opportunities in both UK and Canada.

The creation of genetically modified (transgenic) animal models, primarily mice and rats, has revolutionised our understanding of human disease. Transgenic biotechnologies utilise large numbers of animals: both females and males to generate embryos for genetic manipulation, females to provide a host uterus to support the development of transgenic embryos, and infertile males to induce so-called 'pseudopregnancy' (a process by which females' uterus becomes receptive to transferred embryos) in recipient females. In 2017, 1.69 million UK Home Office regulated procedures were conducted on mice destined for use in such transgenic breeding programmes. Therefore, there is a great market demand for new technologies which can both improve procedural efficiency and markedly reduce experimental animal pain and distress. Mouse embryos for research/breeding programmes are generated using donor females by a process known as superovulation, which aims to maximise oocyte/embryo yield per female. Currently, the procedure involves injecting hormones into the abdominal cavity of female mice to stimulate the growth of ovarian follicles and eggs. The latter are subsequently either fertilised through natural mating or harvested and fertilised in vitro. However, successful superovulation is inherently variable, with yields and quality varying across different operators and batches of hormones. Moreover, intra-abdominal injections are painful and distressing for animals such that users have an ethical and legal responsibility under the 3Rs principles ('Replacement, Reduction, Refinement') to use alternative methods if available. Ostara have identified a market opportunity for developing a high-quality replacement for the hormones used in superovulation (using small molecules called aptamers) as well as moving away from intra-abdominal injections by delivering their active agents vaginally (which is not achievable using current hormone treatments). This novel approach can significantly improve the reliability of superovulation through the use of quality-controlled metered dose hormone alternatives whilst reducing pain and distress by using a minimally invasive agent delivery route.

The creation of genetically modified animals, primarily mice and rats, has revolutionised our understanding of disease processes in animal models. Transgenic biotechnologies utilise large numbers of animals: females and males to generate embryos for genetic manipulation, females to provide a host uterus to support the development of embryos, and infertile males to induce ‘pseudopregnancy’ in recipient females. In the UK alone, 1.8 million mice were used in breeding programmes for production of transgenic mice in 2012 Scientists are required to comply with the principle of the “Three Rs” (Replacement Reduction and Refinement) to minimize the number of animals used in experimentation and to reduce pain and suffering. Ostara received an IUK Development of Prototype grant to develop a vaginal pessary system that supersedes the use of vasectomised males in the induction of pseudopregnancy and enhances transgenic embryo implantation rates in the host mothers. These novel pessaries contain substances that have been identified in mouse seminal fluid that mimic the beneficial effects of semen without the need for vasectomised males or the large numbers of female mice needed to produce enough pseudopregnant mice. A successful Experimental Development project will enable Ostara to complete development and introduce the product to market. If successful it will reduce the numbers of mice used in experimentation by 75-80% and save UK research establishments around £84M per year

The creation of genetically modified animals, primarily mice and rats, has revolutionised understanding of disease processes in animal models. Transgenic biotechnologies utilise large numbers of animals: females and males to generate embryos for genetic manipulation, females to provide a host uterus to support the development of embryos, and infertile males to induce ‘pseudopregnancy’ in recipient females. In the UK alone, 1.2 million mice were used in breeding programmes for production of transgenic mice in 2014. Scientists are required to comply with the principle of the “Three Rs” (Replacement Reduction and Refinement) to minimize the number of animals used in experimentation and to reduce pain and suffering. Ostara has developed a patented pessary system that supersedes the use of vasectomised males in the induction of pseudopregnancy and enhances transgenic embryo implantation rates in the host mothers. The project will see this breakthrough technology demonstrated and promoted globally: the objective of gaining widespread dissemination, adoption and tests can produce an 80% reduction mice numbers.

In the UK alone, 1.8 million mice were used in breeding programmes for production of transgenic mice in 2012, according to Home office figures (about 48% of all animal used in research). The creation of genetically modified animals, primarily mice and rats, has revolutionised our understanding of disease processes in animal models. Transgenic biotechnologies utilise large numbers of animals: females and males to generate embryos for genetic manipulation, females to provide a host uterus to support the development of embryos, and infertile males to induce ‘pseudopregnancy’ in recipient females. Pseudopregnancy is necessary for the uterus to become receptive to transplanted embryos and is achieved by mating foster females with a vasectomised (infertile) male, whose seminal fluid contains an active array of proteins and other factors. Whilst we can’t replace females for superovulation and pregnancy, we have demonstrated in a previous Proof of Concept study that vasectomised males can be replaced altogether. The objective of this project is the development of a prototype vaginal pessary system that supersedes the use of vasectomised males in the induction of pseudopregnancy and enhances transgenic embryo implantation rates in the host mothers. These novel pessaries contain substances that have been identified in mouse seminal fluid that mimic the beneficial effects of semen without the need for vasectomised males or the large numbers of female mice needed to produce enough pseudopregnant mice.