Bilateral BBSRC-FAPESP: Understanding novel conceptus-maternal communication is the key to improving pregnancy outcome in cattle.

我们知道，如果我们要用减少的资源养活越来越多的人口，农业和粮食安全至关重要。极大地影响牛肉和奶牛养殖业的经济可持续性的一个因素是，小母牛或奶牛需要多长时间来建立和维持成功的早孕。提高奶牛和肉牛的繁殖力可以提高农业效率，并长期减少对全球农业的影响。牛妊娠丢失的一个主要来源发生在怀孕的前3周，具体何时发生胚胎丢失的问题尚不清楚。我们所知道的是，胚胎和母体子宫环境之间的成功沟通对于成功的早期怀孕至关重要。有三个关键的相互作用需要发生：1)激素黄体酮需要作用于子宫内膜(子宫内部的组织)，为胚胎提供合适的环境，2)胚胎必须经历一个只有在子宫中才有可能的快速生长期，即我们不能在实验室中概括这一点；3)胚胎必须成功地向母亲发出信号，以维持早期怀孕。在过去的几年里，我的工作重点是使用一种特定类型的技术来帮助解决子宫环境和胚胎(形成小牛的胚胎和形成胎盘的胚外膜)之间如何相互作用的问题。我使用的技术主要集中在转录组学和蛋白质组学上。这些技术不是研究一种基因或蛋白质在特定条件下(例如在怀孕早期)如何变化，而是允许我们研究许多基因和/或蛋白质在早期怀孕期间的表达如何变化。这给了我们一个更广泛的图景，无论是在成功的早期怀孕期间，还是在早期妊娠丢失发生的时候。我的研究主要集中在1)特定荷尔蒙孕酮在提供良好或不足的子宫环境以促进成功早孕方面所起的作用2)母体环境如何对受孕做出反应以及3)如果我们能够使用这些我们已经确定在受孕和子宫内膜之间相互作用的基因或蛋白质在非侵入性样本基质中检测成功的早孕。最近，我的工作发现了关键的蛋白质和分子，包装在囊泡中，可以从一种细胞类型(如受孕)释放出来，并改变不同的细胞类型，如子宫内膜。我还展示了，与女性相比，当男性胚胎存在时，这些相互作用发生的方式可能会不同。研究计划的目标是确定这些囊泡的哪些成分被子宫内膜吸收并改变其功能。我们还将确定这些囊泡在怀孕成功可能性不同的胚胎(与使用辅助生殖技术产生的成功机会较小的胚胎相比，在动物中产生的胚胎质量较高)之间的沟通有何不同。我们还将研究男性和女性的概念如何以不同的方式相互传递信号。总而言之，这项工作的结果将导致1)加强对是什么导致怀孕成功/胚胎丢失的理解，2)防止胚胎丢失的新干预目标，以及3)成功早期怀孕的标志。

We know that Agriculture and Food security are of critical importance if we are to feed an increasing population with reduced resources. One factor that greatly affects the economic sustainability of both beef and dairy farming is the length of time it takes for either heifers or cows to establish and maintain successful early pregnancy. Increasing fertility in dairy and beef cattle can improve agriculture efficiency with a long term decrease in agriculture impacts worldwide. A major source of pregnancy loss in cattle occurs in the first 3 weeks of pregnancy and the question of when exactly this embryo loss occurs is unknown. What we do know is that successful communication between the embryo and the maternal uterine environment is crucial for successful early pregnancy. There are three key interactions that need to occur 1) the hormone progesterone needs to act on the endometrium (the tissue that lines the inner part of the uterus) to provide a suitable environment to host the embryo, 2) the embryo must undergo a rapid period of growth which is only possible in the uterus i.e. we cannot recapitulate this in the lab and 3) the conceptus must successfully signal its presence to the mother to sustain early pregnancy.Over the last number of years my work has focused on using a specific type of technology to help address the question of how the uterine environment and the conceptus (which is the embryo proper that forms the calf and the extra-embryonic membrane which forms the placenta) interact with one another. The technologies I have use have focused on transcriptomics and proteomics. Instead of investigating how one gene or protein changes in a given condition e.g. in early pregnancy these technologies allow us to investigate how the expression of lots of genes and/or proteins change in early pregnancy. This gives us a much broader picture of what is occurring both during successful early pregnancy, but also when early pregnancy loss occurs. The main focus of my research has been on 1) the role that a specific hormone progesterone plays in providing a good or insufficient uterine environment to promote successful early pregnancy 2) how the maternal environment responds to the conceptus and 3) if we can use these gene or proteins we have identified as interacting between the conceptus and the endometrium to detect successful early pregnancy in a non-invasive sample matrix.More recently my work has identified that key proteins and molecules, packaged in vesicles that can be released from one cell type e.g. the conceptus and alter a different cell type e.g. the endometrium. I have also shown that the way in which these interactions occur may be different when a male conceptus is present compared to a female conceptus.The objectives of the research program are to determine what components of these vesicles are taken up by the endometrium and alter its function. We will also determine how the communication by these vesicles differs between embryos that have different likely hood of pregnancy success (those generated in an animal which are of high quality compared with those generated using assisted reproductive technologies which have less chance of success). We will also examine how male and female conceptuses signal in a different manner to one another. Collectively the results from this work will lead to 1) enhanced understanding of what drives pregnancy success/ embryo loss, 2) novel targets to intervene to prevent embryo loss and 3) markers of successful early pregnancy.