In vitro embryo production in animal breeding: Enhancing oocyte quality from peri-pubertal donors to promote biosecure and sustainable food production

未来30年，世界人口将从70亿增加到90亿。肉类(一半以上来自猪和牛)和牛奶(几乎全部来自牛)的人均消费量也将增加20%。这将给全球的食品生产商带来无法容忍的需求，他们被要求在更短的时间内用更少的动物生产更多的肉类和牛奶。畜牧业生产对全球变暖也有18%的贡献。利用基因选择来提高牲畜生产力提供了最可持续的手段，以满足全球对动物产品日益增长的需求，并减轻对环境的有害影响。英国在农畜遗传学方面处于世界领先地位，但未来基因变化的速度是一个挑战。使用先进的生殖技术，如体外受精(IVF)胚胎，在这方面有几个好处。许多试管受精胚胎可以从少数精英女性身上产生，这让我们能够更有选择性。在受精几天后，也可以在试管受精胚胎中筛选出遗传特征。这加快了选择的时间，防止了不想要的动物的出生，并有一个额外的优势，即促进了宝贵的遗传种群的生物银行，以及低成本、高福利和生物安全的国际运输。来自年轻(青春期)捐赠者的试管受精胚胎可以通过进一步减少选择的时间而导致遗传改善率的更大提高。因此，这个项目的最终目标是让猪和牛的试管受精效果更好，因为母亲的年龄越小越好。猪和牛的胚胎也是研究人类试管受精的良好模型。通过更好地了解体外受精过程中发生的生物学过程，特别是对青春期供者来说，我们的目标是显著提高这一过程的整体效率，从而使其成为未来基因选择的首选方法。我们相信，我们可以通过集中精力减少胚胎中严重的遗传异常(即额外或缺失的染色体)的水平来改善这两个物种的这一过程，这些异常通过细胞内许多称为线粒体的小结构与能量代谢联系在一起。因此，我们的中心问题是，我们能否通过改进卵母细胞(卵子)成熟过程来提高胚胎的质量？在奶牛身上，我们还将研究用于刺激卵巢的较温和的治疗方案(类似于人类试管受精)，希望这也将改善卵子和胚胎的质量，以及旨在实现同样目的的饮食方案。这应该会减少我们胚胎中总基因组失衡、新陈代谢问题和压力的水平，从而提高它们的发育潜力。我们的第二个问题是，这是否真的导致胚胎移植后“农场”活产率的提高。通过将我们的新试管受精制度与筛选和移除含有线粒体和染色体异常的胚胎相结合，我们的目标是建立这一目标。在这一联系建议中，学术界和业界合作伙伴在近年来合作开发猪和牛的试管受精方面取得了成功的记录。目前的应用将见证这项技术的改进，因为我们解决了与体外受精过程中的新陈代谢和染色体行为相关的发育生物学的一个基本方面。我们的行业合作伙伴将与我们并肩工作，收集鸡蛋，进行饮食研究，并进行大规模的农场胚胎移植，以证明活出生率的改善。因此，这一应用的独特“卖点”是方法、学者和实业家的新颖组合，将确保项目从研究实验室到农场的所有方式的成功。

The world population will increase from 7 to 9 billion in the next 30 years. Consumption of meat (over half of which comes from pigs and cattle) and milk (nearly all from cattle) will also rise by 20% per person. This will place an intolerable demand on food producers globally who are charged with generating more meat and milk from fewer animals, in less time. Livestock production also contributes 18% of global warming. Using genetic selection to improve livestock productivity offers the most sustainable means to match increased global demand for animal products and to mitigate harmful effects to the environment. The UK leads the world in farm-animal genetics, but the pace at which genetic change must occur in future represents a challenge. The use of advanced reproductive technologies such as in vitro fertilised (IVF) embryos offers several benefits in this regard. Many IVF embryos can be generated from a small number of elite females allowing us to be more selective. Genetic traits can also be screened in IVF embryos just a few days after fertilisation. This speeds up the time to selection, prevents the birth of unwanted animals and has the added advantage of facilitating bio-banking of genetically precious stock, together with low-cost, high-welfare and biosecure international transportation. IVF embryos from young (peri-pubertal) donors can lead to a greater increase in the rate of genetic improvement by reducing the time to selection even further. The ultimate aim of this project, therefore, is to make pig and cattle IVF work better from mothers that are as young as possible. Pig and cattle embryos are also good models for studying human IVF. By developing a better understanding of the biological processes that occur during IVF, particularly for the peri-pubertal donor, we aim to improve significantly the overall efficiency of this procedure, thereby making it the method of choice for genetic selection in future. We believe that we can improve the process in both species by focussing on reducing the level of gross genetic abnormalities (i.e. extra or missing chromosomes) in the embryo which is linked to energy metabolism by numerous small structures within the cell called mitochondria. Our central question therefore is can we improve the quality of the embryo produced by improving the oocyte (egg) maturation process? In cows, we will also investigate milder therapeutic regimes used to stimulate ovaries (similar to human IVF) in the hope that this will also improve egg and embryo quality, together with dietary regimes designed to do the same. This should reduce levels of gross genomic imbalance, metabolic problems and stress in our embryos, thereby increasing their developmental potential. Our second question is whether this actually leads to "on-farm" improvements in live-birth rates following embryo transfer. By combining our new regimes of IVF with screening and removal of embryos containing mitochondrial and chromosomal abnormalities we aim to establish this.The academic and industry partners in this LINK proposal have enjoyed a successful track-record of collaboration in developing pig and cattle IVF in recent years. The current application will witness a step-change in improvements to this technology as we address a fundamental aspect of developmental biology associated with metabolism and chromosome behaviour during IVF. Our industry partners will work alongside us to collect eggs, undertake dietary studies and large-scale on farm embryo transfers to demonstrate improvements in live-birth rates. The unique "selling point" of this application, therefore, is the novel combination of approaches, academics and industrialists that will ensure success of the project all the way from research lab to farm.