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

双边 BBSRC-FAPESP：了解新概念-母体沟通是改善牛妊娠结局的关键。

• 批准号: BB/R017522/1
• 负责人: Niamh Forde
• 金额: $ 71.16万
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR017522%2F1
• 关键词: Bilateral; BBSRC; FAPESP; Understanding; novel

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.

我们知道，如果我们要以减少的资源来养活越来越多的人口，那么农业和粮食安全至关重要。极大地影响牛肉和乳制品耕种的经济可持续性的一个因素是小母牛或母牛建立和维持成功的早期怀孕所需的时间。奶牛和牛牛的生育能力的增加可以提高农业效率，而全球农业影响的长期降低。牛怀孕的主要来源发生在怀孕的前三周，以及何时发生这种胚胎丧失的问题尚不清楚。我们所知道的是，胚胎和母体子宫环境之间的成功交流对于成功怀孕至关重要。需要发生三个关键的相互作用1）需要在子宫内膜（将子宫内部内部的组织（组织组织）采取的激素孕激素需要提供适当的环境来托管胚胎，2）2）胚胎必须快速的生长时期才能经历一段时间，这只能在您的概念中延长概念。我的工作集中在使用特定类型的技术来帮助解决子宫环境和概念（这是形成小腿的胚胎适当的胚胎和形成胎盘的外胚膜外膜）如何相互作用的问题。我使用的技术专注于转录组学和蛋白质组学。而不是研究一个基因或蛋白质在给定条件下如何变化，例如在怀孕初期，这些技术使我们能够研究怀孕初期的许多基因和/或蛋白质的表达。这为我们提供了更广泛的了解，即成功怀孕期间发生的事情，以及早期怀孕丧失时。我的研究的主要重点是1）特定的激素孕激素在提供良好或不足的子宫环境方面起作用以促进成功的早期怀孕2）孕产妇环境对概念的反应如何； 3）如果我们可以使用这些基因或蛋白质来使用这些基因或蛋白质，我们可以在概念和子宫内部进行不合时宜的临界剂，以识别成功的早期术语。和分子，包装在可以从一种细胞类型中释放的囊泡中，例如概念并改变了不同的细胞类型，例如子宫内膜。我还表明，与女性概念相比，存在男性概念时，这些相互作用的发生方式可能有所不同。研究计划的目标是确定这些囊泡的哪些组成部分被子宫内膜占据并改变其功能。我们还将确定这些囊泡的通信在具有不同妊娠成功的引擎盖（在动物中产生的胚胎的胚胎与使用辅助生殖技术产生的动物相比，其质量高的动物产生的胚胎之间的交流如何）。我们还将研究男性和女性概念如何以不同的方式发出信号。总的来说，这项工作的结果将导致1）增强对促进妊娠成功/胚胎丧失的理解，2）介入以防止胚胎丧失的新目标； 3）成功的早期怀孕。

项目成果

Endometrium-on-a-chip reveals the endometrial transcriptome, and protein content of secretome are altered by changes in circulating concentrations of insulin and glucose in vitro

子宫内膜芯片揭示子宫内膜转录组，分泌组的蛋白质含量会因体外胰岛素和葡萄糖循环浓度的变化而改变

• DOI: 10.1101/2020.11.03.361774
• 发表时间: 2020
• 作者: De Bem T

Sex-bias in utero alters ovarian reserve but not uterine capacity in female offspring

子宫内的性别偏见会改变女性后代的卵巢储备功能，但不会改变子宫容量

• DOI: 10.1101/2022.07.11.499550
• 发表时间: 2022
• 作者: Geijer-Simpson A

MicroRNAs emerging coordinate with placental mammals alter pathways in endometrial epithelia important for endometrial function.

• DOI: 10.1016/j.isci.2023.106339
• 发表时间: 2023-04-21
• 期刊: ISCIENCE
• 影响因子: 5.8
• 作者: Hume, Laura;Edge, Jessica C.;Tinning, Haidee;Wang, Dapeng;Taylor, Alysha S.;Ovchinnikov, Vladimir;Geijer-Simpson, Annika, V;Vrljicak, Pavle;Brosens, Jan J.;Lucas, Emma S.;Simpson, Nigel A. B.;Shillito, Jayne;Forbes, Karen;O'Connell, Mary J.;Forde, Niamh
• 通讯作者: Forde, Niamh

Endometrium On-a-Chip Reveals Insulin- and Glucose-induced Alterations in the Transcriptome and Proteomic Secretome.

• DOI: 10.1210/endocr/bqab054
• 发表时间: 2021-06-01
• 期刊: Endocrinology
• 影响因子: 4.8
• 作者: De Bem THC;Tinning H;Vasconcelos EJR;Wang D;Forde N
• 通讯作者: Forde N

A burst of genomic innovation at the origin of placental mammals mediated embryo implantation.

胎盘哺乳动物起源的基因组创新爆发介导了胚胎植入。

• DOI: 10.5281/zenodo.7686456
• 发表时间: 2023
• 作者: O'Connell M