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。

基本信息

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

项目摘要

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养活不断增加的人口，农业和粮食安全至关重要。极大影响牛肉和奶牛养殖经济可持续性的因素之一是小母牛或奶牛建立和维持成功早期妊娠所需的时间长度。提高奶牛和肉牛的繁殖力可以提高农业效率，长期减少对全球农业的影响。牛妊娠损失的一个主要来源发生在怀孕的前 3 周，而这种胚胎损失究竟何时发生的问题尚不清楚。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妊娠至关重要。需要发生三种关键的相互作用：1) 激素孕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) 胚胎必须经历快速的生长周期只有在子宫中才有可能，即我们无法在实验室中重现这一点，并且 3) 孕体必须成功向母亲发出其存在的信号以维持早期妊娠。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，可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胎外膜）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在给定条件下如何变化，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期间以及早孕流产发生时发生的情况有更广泛的了解。我研究的主要重点是 1) 特定激素黄体酮在提供良好或不足的子宫环境以促进成功早孕方面所发挥的作用 2) 母体环境如何对受孕做出反应 3) 我们是否可以利用这些我们已经确定了在受孕体和子宫内膜之间相互作用的基因或蛋白质，以在非侵入性样本基质中检测成功的早期妊娠。最近我的工作已经确定了包装在囊泡中的关键蛋白质和分子，这些蛋白质和分子可以从一个囊泡中释放出来。细胞类型例如概念并改变不同的细胞类型，例如子宫内膜。我还表明，与女性受孕相比，当男性受孕时，这些相互作用发生的方式可能有所不同。该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。我们还将确定具有不同妊娠成功率的胚胎（在动物中产生的胚胎质量较高，而使用辅助生殖技术产生的胚胎成功率较低）之间这些囊泡的通讯有何不同。我们还将研究男性和女性概念如何以不同的方式彼此发出信号。总的来说，这项工作的结果将导致 1) 增强对推动妊娠成功/胚胎丢失的因素的理解，2) 预防胚胎丢失的新干预目标，以及 3) 成功早期妊娠的标志。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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
期刊：
影响因子：
0
作者：
De Bem T
通讯作者：
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
期刊：
影响因子：
0
作者：
Geijer-Simpson A
通讯作者：
Geijer-Simpson A

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

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

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。