Impact of mycotoxins of agricultural relevance on reproductive cell biology in cattle

可持续的畜牧业生产对于实现本世纪预计的人口快速增长的粮食安全至关重要。因此，随着奶制品行业为人类消费提供关键营养素，对动物蛋白的需求将继续上升。霉菌毒素是由真菌产生的有毒代谢物，对全球可持续动物生产构成重大挑战。在奶牛群中，真菌毒素如脱氧雪腐镰刀菌烯醇(DON)和玉米赤霉烯酮(ZEN)在饲料中非常普遍，但由于暴露水平较低，临床上没有观察到真菌中毒的症状。因此，它们对牛繁殖性能的潜在影响尚不清楚。生产小牛的能力直接影响奶牛生产牛奶的能力，进而影响农场的盈利能力。因此，有效的繁殖性能对可持续的乳品生产至关重要，而早期胚胎死亡会削弱这一点，占妊娠损失的40%，有证据表明，牛在怀孕的第一周(即植入前胚胎发育期间，此时牛胚胎达到约150个细胞的囊胚期)发生胚胎损失。在猪的体外研究表明，DON和ZEN可以损害卵母细胞(卵)的发育能力(即卵母细胞发育成植入前胚胎的能力)，但它们对牛卵母细胞的发育能力的影响几乎是未知的。因此，这个项目的目的是利用代表现实生活中暴露的浓度的生理学相关值来产生关于DON和ZEN对牛卵母细胞发育能力影响的新的机制知识。细胞和分子终点将在植入前胚胎生产的体外牛模型中进行分析。该项目将使用从商业屠宰场收集的牛卵巢提取的卵母细胞的体外模型。卵巢是养牛业的副产品；因此，不会为了这个项目而宰杀任何动物。该项目将能够确定霉菌毒素的作用机制，为未来的治疗开发创造机会，以防止早孕丢失，从而改善动物福利和农民的盈利能力(即SAF重点领域的“可持续农业系统”和“作物和养殖动物健康”)。气候变化导致霉菌毒素作物污染增加的预测模型进一步突显了这项研究的相关性。

Sustainable animal production is critical to achieve food security for the rapid population growth predicted for this century. As such, the demand for animal protein will continue to rise, with the dairy sector providing key nutrients for human consumption. Mycotoxins are toxic metabolites produced by fungi that represent a major challenge for sustainable animal production worldwide. In dairy cattle herds, mycotoxins such as deoxynivalenol (DON) and zearalenone (ZEN) are highly prevalent in feedstuffs, but clinical presentation of mycotoxicosis is not observed due to the low level of exposure. Hence, their potential impact on cattle reproductive performance is unknown. The capability to produce a calf has a direct impact on the ability of the cow to produce milk and in turn on farm profitability. Hence, efficient reproductive performance is pivotal for sustainable dairy production and it is impaired by early embryonic death, accounting for loss of 40% of pregnancies, with evidence highlighting occurrence of embryonic losses in the first week of pregnancy in cattle (i.e. during preimplantation embryo development, when the bovine embryo reaches the blastocyst stage with around 150 cells). In vitro studies in pigs showed that DON and ZEN can impair oocyte (egg) development competence (i.e. the capacity of an oocyte to develop into a preimplantation embryo), but their effects on the developmental competence of bovine oocytes is virtually unknown. This project therefore aims to generate novel mechanistic knowledge on the impact of DON and ZEN on bovine oocyte developmental competence using physiologically relevant values using concentrations representative of real-life exposure. Cellular and molecular endpoints will be analysed in an in vitro bovine model of preimplantation embryo production. The project will use an in vitro model with oocytes extracted from cattle ovaries collected from a commercial abattoir. The ovaries are a by-product of the cattle industry; hence, no animal will be killed for the sake of this project. The project would allow for the mechanisms of action of mycotoxins to be determined, generating opportunities for future therapeutic development to prevent early pregnancy loss, and hence improving animal welfare and profitability for farmers (i.e. the SAF focus areas 'sustainable agricultural systems' and 'crop and farmed animal health'). The relevance of this research is further highlighted by prediction models indicating an increase in mycotoxin crop contamination as a consequence of climate change.