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

世界人口将在未来30年从70亿增加到90亿。肉类（其中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%。这将对全球食品生产商提出难以忍受的要求，他们必须在更短的时间内用更少的动物生产更多的肉和奶。畜牧业对全球变暖也有18%的贡献。利用遗传选择提高牲畜生产力是满足全球对动物产品日益增长的需求和减轻对环境的有害影响的最可持续手段。英国在农场动物遗传学方面处于世界领先地位，但未来基因变化必须发生的速度是一个挑战。使用先进的生殖技术，如体外受精（IVF）胚胎，在这方面提供了几个好处。许多体外受精胚胎可以从少数优秀女性中产生，这使我们更具选择性。遗传特征也可以在受精后几天的体外受精胚胎中进行筛选。这加快了选择的时间，防止了不想要的动物的出生，并具有促进遗传珍贵种群生物银行的额外优势，以及低成本，高福利和生物安全的国际运输。来自年轻（青春期前后）供体的体外受精胚胎可以通过进一步减少选择时间来提高遗传改良率。因此，这个项目的最终目的是使猪和牛的体外受精从尽可能年轻的母亲那里获得更好的效果。猪和牛的胚胎也是研究人类体外受精的良好模型。通过更好地了解体外受精过程中发生的生物学过程，特别是对于青春期前后的供体，我们的目标是显著提高这一过程的整体效率，从而使其成为未来遗传选择的首选方法。我们相信，通过专注于降低胚胎中与细胞内称为线粒体的许多小结构的能量代谢有关的总体遗传异常（即额外或缺失的染色体）的水平，我们可以改善这两个物种的过程。因此，我们的核心问题是，我们能否通过改善卵母细胞成熟过程来提高胚胎的质量？在奶牛中，我们还将研究用于刺激卵巢的温和治疗方案（类似于人类体外受精），希望这也能提高卵子和胚胎的质量，同时设计出同样的饮食方案。这将减少我们胚胎中的总体基因组失衡、代谢问题和压力水平，从而增加它们的发育潜力。我们的第二个问题是，这是否真的会导致胚胎移植后活产率的“农场”改善。通过将我们的试管婴儿新体制与含有线粒体和染色体异常的胚胎的筛选和去除相结合，我们的目标是建立这一点。近年来，LINK提案中的学术和行业合作伙伴在发展猪和牛体外受精方面取得了成功的合作记录。当前的应用将见证该技术的逐步改进，因为我们解决了与体外受精期间代谢和染色体行为相关的发育生物学的基本方面。我们的行业合作伙伴将与我们一起收集卵子，进行饮食研究和大规模农场胚胎移植，以证明活产率的提高。因此，这一应用的独特“卖点”是方法、学者和实业家的新颖结合，这将确保项目从研究实验室到农场的整个过程都取得成功。

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.