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Achieving a successful pregnancy: Epigenetic regulation of fetal-maternal signaling

实现成功妊娠：胎儿-母体信号传导的表观遗传调控

基本信息

批准号：
BB/J015156/1
负责人：
Rosalind John
金额：
$ 51.22万
依托单位：
CARDIFF UNIVERSITY
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2012
资助国家：
英国
起止时间：
2012 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FJ015156%2F1
关键词：
Achieving successful pregnancy Epigenetic regulation

项目摘要

Pregnancy, which is experienced by over 700,000 women per year in the United Kingdom, is a dynamic, exquisitely coordinated process involving systemic and local changes in the mother to accommodate the metabolically demanding and immunogenic fetus. Disorders of human pregnancy, such as stillbirth, low birth weight, preterm birth and maternal diabetes may occur as a consequence of poor or inappropriate adaptation to pregnancy illustrating the importance of this highly regulated process, both for the health of the mother and for the well being of her children. Many of the endocrine and metabolic changes that occur in the mother during pregnancy can be directly attributed to signals originating from the placenta. We are investigating the role of an imprinted gene in regulating these signals from the placenta to the mother. Imprinted genes, which are expressed in mammals from only one parental allele, play an important role in regulating embryonic growth and placental support. In this study, we will use a model system in which we have engineered changes in the expression of the imprinted gene, Phlda2, in the placenta. Changing the amount of Phlda2 alters the composition of the placenta such that there is either decreased or increased expression of placental hormones that signal to the mother. Consequently mothers carrying these pups will be exposed to either too little or too much of these hormones during pregnancy. It is well known that in human pregnancies, abnormal levels of these hormones in maternal serum are associated with low birth weight and, in some case, fetal loss. Indeed, we observe both low birth weight and some evidence fetal loss when our mothers receive too little of the placental signals. In this proposal, we will simply ask whether mothers carrying pups with elevated expression or loss of expression of Phlda2 show indicators of abnormal adaptation to pregnancy. What is remarkable about this study is that we will be able to show that an imprinted gene in the fetus can manipulate the mother's physiology during pregnancy. Additionally, we will provide data on the consequences of aberrant expression of Phlda2 on the health and well being of both the mother and her offspring.

在英国，每年有超过700，000名妇女经历妊娠，这是一个动态的、精密协调的过程，涉及母亲的全身和局部变化，以适应代谢要求和免疫原性的胎儿。人类妊娠疾病，如死胎、低出生体重、早产和母体糖尿病，可能是对妊娠适应不良或不适当的结果，这说明了这一高度调节的过程对母亲健康及其子女福祉的重要性。许多内分泌和代谢的变化，发生在母亲怀孕期间可以直接归因于来自胎盘的信号。我们正在研究印记基因在调节从胎盘到母亲的这些信号中的作用。印记基因在哺乳动物中仅由一个亲本等位基因表达，在调节胚胎生长和胎盘支持方面发挥重要作用。在这项研究中，我们将使用一个模型系统，在该系统中，我们设计了胎盘中印记基因Phlda2表达的变化。改变Phlda2的量会改变胎盘的组成，从而减少或增加向母亲发出信号的胎盘激素的表达。因此，携带这些幼崽的母亲在怀孕期间会接触到太少或太多的这些激素。众所周知，在人类妊娠中，母体血清中这些激素的异常水平与低出生体重有关，在某些情况下，与胎儿丢失有关。事实上，我们观察到低出生体重和一些证据胎儿损失时，我们的母亲收到太少的胎盘信号。在这个提议中，我们将简单地询问携带Phlda2表达升高或表达缺失的幼崽的母亲是否显示出对妊娠的异常适应的指标。这项研究值得注意的是，我们将能够证明胎儿中的印记基因可以在怀孕期间操纵母亲的生理机能。此外，我们将提供有关Phlda 2异常表达对母亲及其后代健康和福祉的后果的数据。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Placental PHLDA2 expression is increased in cases of fetal growth restriction following reduced fetal movements.

DOI：
10.1186/s12881-016-0279-1
发表时间：
2016-03-05
期刊：
BMC medical genetics
影响因子：
0
作者：
Janssen AB;Tunster SJ;Heazell AE;John RM
通讯作者：
John RM

Maternal prenatal depression is associated with decreased placental expression of the imprinted gene PEG3.

孕产妇产前抑郁症与印迹基因PEG3的胎盘表达降低有关。

DOI：
10.1017/s0033291716001598
发表时间：
2016-10
期刊：
PSYCHOLOGICAL MEDICINE
影响因子：
6.9
作者：
Janssen, A. B.;Capron, L. E.;O'Donnell, K.;Tunster, S. J.;Ramchandani, P. G.;Heazell, A. E. P.;Glover, V.;John, R. M.
通讯作者：
John, R. M.

Prenatal maternal depression and aberrant placental imprinting

产前母亲抑郁症和胎盘印记异常

DOI：
10.1016/j.psyneuen.2015.07.396
发表时间：
2015
期刊：
Psychoneuroendocrinology
影响因子：
3.7
作者：
Janssen A
通讯作者：
Janssen A

Maternal care boosted by paternal imprinting in mammals.

哺乳动物的父系印记促进了母性护理。

DOI：
10.1371/journal.pbio.2006599
发表时间：
2018-07
期刊：
PLoS biology
影响因子：
9.8
作者：
Creeth HDJ;McNamara GI;Tunster SJ;Boque-Sastre R;Allen B;Sumption L;Eddy JB;Isles AR;John RM
通讯作者：
John RM

A Role for the Placenta in Programming Maternal Mood and Childhood Behavioural Disorders.

DOI：
10.1111/jne.12373
发表时间：
2016-08
期刊：
Journal of neuroendocrinology
影响因子：
3.2
作者：
Janssen AB;Kertes DA;McNamara GI;Braithwaite EC;Creeth HD;Glover VI;John RM
通讯作者：
John RM

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Rosalind John其他文献

Epigenetic regulation of placental endocrine function

DOI：
10.1016/j.placenta.2014.06.174
发表时间：
2014-09-01
期刊：
Conference abstract
影响因子：
作者：
Simon Tunster;Hugo Creeth;Rosalind John
通讯作者：
Rosalind John

Phlda2 – an imprinted growth restricting gene that drives metabolic programming

DOI：
10.1016/j.placenta.2013.06.203
发表时间：
2013-09-01
期刊：
Conference abstract
影响因子：
作者：
Simon Tunster;Mathew Van de Pette;Ben Tycko;Rosalind John
通讯作者：
Rosalind John

Prenatal adversity drives placental endocrine insufficiency impacting maternal caregiving and offspring behaviour

DOI：
10.1016/j.placenta.2021.07.029
发表时间：
2021-09-01
期刊：
Conference abstract
影响因子：
作者：
David Harrison;Hugo Creeth;Hannah Tyson;Raquel Boque Sastre;Susan Hunter;Dominic Dwyer;Anthony Isles;Rosalind John
通讯作者：
Rosalind John