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不断增加的人口，农业和粮食安全至关重要。一个极大地影响牛肉和奶牛养殖经济可持续性的因素是小母牛或奶牛建立和维持成功的早期妊娠所需的时间长度。提高奶牛和肉牛的生育力可以提高农业效率，长期减少对全球农业的影响。牛妊娠丢失的主要原因发生在妊娠的前3周，胚胎丢失的确切时间尚不清楚。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妊娠至关重要。需要发生三个关键的相互作用：1)黄体酮激素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)胚胎必须经历一段只有在子宫内才有可能的快速生长时期，即我们无法在实验室中概括这一点；3)受孕者必须成功地向母亲发出信号，以维持早期妊娠。在过去的几年里，我的工作一直集中在使用一种特定类型的技术来帮助解决子宫环境和概念（即形成小牛的胚胎本身和形成胎盘的胚外膜）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。而不是研究一个基因或蛋白质如何在特定条件下变化，例如在怀孕早期，这些技术使我们能够研究许多基因和/或蛋白质的表达在怀孕早期如何变化。这让我们对成功早孕和早孕流产期间发生的情况有了更广泛的了解。我的研究主要集中在1)孕激素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3)如果我们可以使用这些基因或蛋白质，我们已经确定在受孕和子宫内膜之间相互作用，在非侵入性样本基质中检测成功的早孕。最近，我的工作已经确定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（如子宫内膜）中释放出来，并改变不同的细胞类型（如子宫内膜）。我还展示了当一个男性概念和一个女性概念出现时，这些相互作用发生的方式可能不同。研究计划的目的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具有不同怀孕成功率的胚胎（那些在高质量的动物中产生的胚胎与使用辅助生殖技术产生的胚胎相比成功率较低）之间的通信是如何不同的。我们还将研究男性和女性概念如何以不同的方式相互传递信号。总的来说，这项工作的结果将导致1)加强对驱动妊娠成功/胚胎丢失的原因的理解，2)干预以防止胚胎丢失的新目标，3)早期妊娠成功的标志。

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.