Defining the impact of paternal nutrition on fetal growth regulation

定义父亲营养对胎儿生长调节的影响

• 批准号: BB/R003556/1
• 负责人: Adam Watkins
• 金额: $ 64.54万
• 依托单位: University of Nottingham
• 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%2FR003556%2F1
• 关键词: Defining; impact; paternal; nutrition; fetal

We know that what a mother eats during pregnancy is important for the development and growth of her child. We also know that a poor diet during pregnancy can increase the risk that her child grows up being overweight, having type-2 diabetes or osteoporosis in adulthood. While the relationship between a mother's diet and the health of her child has been studied in detail, the relationship between a father's diet and his child's health has been neglected.To begin to address this knowledge gap, I conducted a series of experiments in which male mice were fed a low protein diet (LPD; a poor, nutritionally imbalanced diet). I found that adult offspring of LPD fed male mice became over weight, had more body fat and developed symptoms of heart disease and type-2 diabetes. As all the female (mothers) mice were fed the same good quality diet during pregnancy, these changes in offspring health are solely caused by the poor diet of their fathers. Of specific interest was the observation that a paternal LPD increased the weight of his offspring at birth. In human and animal studies we know that being significantly heavier at birth increases the chances of developing heart disease, obesity, diabetes and osteoporosis in adulthood. Therefore, understanding how a father's diet affects the growth of his offspring before birth is central to preventing the development of poor health in adult life. Using my mouse model, I am uniquely positioned to address the question of how a father's diet affects the growth of his offspring before birth. Mice are an excellent model to use for such studies as many of the biological processes regulating metabolism, reproduction, embryo development and offspring health are the same between mice and humans. Using my mouse model, I have identified key changes in embryonic gene expression, fetal growth, bone formation and placental development in response to paternal LPD. These data suggest poor paternal diet affects a range of fundamental biological processes and identify key mechanisms for study in the regulation of offspring development. Therefore, this proposal will expand on my existing mouse paternal diet studies establishing the precise mechanisms through which poor paternal diet affects the development and growth of his offspring prior to birth. In addition, I will determine whether supplementing a poor paternal diet with specific combinations of vitamins can be beneficial for both paternal health and the health of his offspring. Under this proposal, I will first determine how a father's diet affects the development and metabolism of the early embryo. I will measure what the embryo metabolises, the rate at which the embryo develops and look at which proteins the embryo is expressing. This is because we know that changes in early embryo development can affect the growth of the fetus and offspring health in adult life. My second objective is to determine whether offspring growth is influenced by the function of the placenta. Here, I will measure the transport of key nutrients from the mother to her fetus and relate this to all the genes that are expressed within the placenta. These studies will inform on whether a father 'hijacks' the placenta, programming it to enhance the growth of his offspring. A third objective will be to relate paternal diet to the development of his offspring's skeleton. Here, I will use state-of-the-art imaging techniques to measure how offspring skeletons are built, organised and structured, giving important insight into their bone strength in later-life. Finally, I will characterise how a father's diet affects the development of his sperm and the genetic information that is passed from one generation to the next.This work is timely in its focus on the role of a father's diet for the growth and well-being of his offspring. Findings from this study will help men, wishing to become a father, improve their diet and lifestyle for the benefit of their children's health.

我们知道，母亲在怀孕期间吃什么对于孩子的成长和成长很重要。我们还知道，怀孕期间的饮食不佳会增加孩子长大的超重，成年后患有2型糖尿病或骨质疏松症的风险。尽管已经详细研究了母亲的饮食与孩子的健康之间的关系，但父亲的饮食与孩子的健康之间的关系被忽略了。要开始解决这一知识差距，我进行了一系列实验，其中雄性小鼠被喂养出低蛋白质饮食（LPD；较差的，贫穷的营养不平衡饮食）。我发现，成年液化生物的雄性小鼠的成年后代体重过大，体内脂肪更多，并且患有心脏病和2型糖尿病的症状。由于所有雌性（母亲）小鼠在怀孕期间都喂了相同的优质饮食，因此后代健康的这些变化完全是由于父亲的饮食不佳而引起的。特别感兴趣的是，父亲LPD增加了他后代的体重。在人类和动物研究中，我们知道，出生时较重的重量会增加成年后心脏病，肥胖，糖尿病和骨质疏松症的机会。因此，了解父亲的饮食在出生前如何影响他后代的成长对于防止成人健康状况不佳的发展至关重要。使用我的鼠标模型，我唯一地解决了父亲饮食如何影响他后代在出生前的成长的问题。小鼠是小鼠和人类之间的许多生物学过程，用于调节代谢，繁殖，胚胎发育和后代健康的许多生物学过程，是一种出色的模型。使用小鼠模型，我确定了胚胎基因表达，胎儿生长，骨形成和胎盘发育的关键变化，以响应父亲的LPD。这些数据表明，父亲饮食不良影响一系列基本生物学过程，并确定了在调节后代发展的研究的关键机制。因此，该提案将扩大我现有的小鼠父亲饮食研究，以确定父亲饮食在出生前会影响其后代的发展和成长的确切机制。此外，我将确定是否补充不良的父亲饮食，以特定的维生素组合对父亲健康和后代的健康都有益。根据该提议，我将首先确定父亲的饮食如何影响早期胚胎的发展和代谢。我将测量胚胎的代谢，胚胎产生的速率并查看胚胎表达的蛋白质。这是因为我们知道早期胚胎发育的变化会影响胎儿的成长和后代健康。我的第二个目标是确定后代生长是否受胎盘功能的影响。在这里，我将测量关键营养物质从母亲到她的胎儿的运输，并将其与胎盘内表达的所有基因联系起来。这些研究将告知父亲是否“劫持”胎盘，对其进行编程以增强其后代的成长。第三个目标是将父亲饮食与后代骨骼的发展联系起来。在这里，我将使用最先进的成像技术来衡量后代骨骼的建造，有组织和结构化的方式，从而对他们在后期生活中的骨骼强度进行重要洞察力。最后，我将表征父亲的饮食如何影响他的精子的发展以及从一代人传递到第二代的遗传信息。这项工作及时地关注父亲饮食对他后代的成长和福祉的作用。这项研究的结果将帮助男人，希望成为父亲，改善饮食和生活方式，以使孩子的健康受益。

项目成果

Paternal nutritional programming of lipid metabolism is propagated through sperm and seminal plasma.

• DOI: 10.1007/s11306-022-01869-9
• 发表时间: 2022-02-10
• 期刊: Metabolomics : Official journal of the Metabolomic Society
• 作者: Furse S;Watkins AJ;Williams HEL;Snowden SG;Chiarugi D;Koulman A
• 通讯作者: Koulman A

Characterisation of the Paternal Influence on Intergenerational Offspring Cardiac and Brain Lipid Homeostasis in Mice.

• DOI: 10.3390/ijms24031814
• 发表时间: 2023-01-17
• 期刊: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
• 影响因子: 5.6
• 作者: Furse, Samuel;Morgan, Hannah L.;Koulman, Albert;Watkins, Adam J.
• 通讯作者: Watkins, Adam J.

Paternal periconception metabolic health and offspring programming.

• DOI: 10.1017/s0029665121003736
• 发表时间: 2021-10
• 期刊: The Proceedings of the Nutrition Society
• 作者: Nader Eid;Hannah L Morgan;A. Watkins

Dietary protein insufficiency: an important consideration in fatty liver disease?

• DOI: 10.1017/s0007114519003064
• 发表时间: 2020-03-28
• 期刊: BRITISH JOURNAL OF NUTRITION
• 影响因子: 3.6
• 作者: Ampong, Isaac;Watkins, Adam;Griffiths, Helen R.
• 通讯作者: Griffiths, Helen R.

Lipid Traffic Analysis reveals the impact of high paternal carbohydrate intake on offsprings' lipid metabolism.

• DOI: 10.1038/s42003-021-01686-1
• 发表时间: 2021-02-05
• 期刊: Communications biology
• 影响因子: 5.9
• 作者: Furse S;Watkins AJ;Hojat N;Smith J;Williams HEL;Chiarugi D;Koulman A
• 通讯作者: Koulman A