Glucocorticoid exposure during prenatal development: Embryonic modulation and long-term consequences on oxidative stress and aging

产前发育期间的糖皮质激素暴露：胚胎调节以及对氧化应激和衰老的长期影响

基本信息

批准号：
9022970
负责人：
Mark F. Haussmann
金额：
$ 33.98万
依托单位：
BUCKNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-01-01 至 2020-04-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): This application proposes a research project that investigates the mechanisms through which conditions experienced during embryonic development influence disease susceptibility later in life. Adverse prenatal conditions are linked to increased disease prevalence in adults, and this may be mediated in part by increased embryonic exposure to maternal glucocorticoids. Fortunately, the placenta serves as a "metabolic buffer", and it is capable of metabolizing a large portion of glucocorticoids (80- 90%) as they pass from the maternal circulation to the fetal circulation. Unfortunately, it is nearly impossible to examine the direct responses of developing embryos to increased glucocorticoids, because changes in glucocorticoid levels also alter maternal physiology, which may indirectly influence embryonic development. This proposal utilizes a novel avian study system, the Japanese quail (Coturnix japonica), where embryonic development takes place outside of the maternal environment to examine (i) how embryos regulate exposure to maternal glucocorticoids, (ii) how embryos respond to increased glucocorticoid exposure, and (iii) the long- term effects of increased glucocorticoid exposure. This study will test the hypothesis that increased embryonic exposure to glucocorticoids alters glucocorticoid responses to adverse conditions and results in life-long effects on oxidative stress, telomere shortening, and survival in offspring. Using LC/MS/MS to quantify a wide range of steroids, the effect of increased glucocorticoid exposure on the embryonic endocrine environment will be examined. Longitudinal studies will be used to characterize the effects of increased glucocorticoid exposure on glucocorticoid production, oxidative stress, and telomere dynamics throughout the avian lifespan. At the end of this project, the research team will have identified the metabolic pathway through which embryos regulate their exposure to maternally-derived glucocorticoids, characterized the response of embryonic endocrine environment in response to increased glucocorticoid exposure, and examined the consequences of this exposure on life-long stress. Results from this work will greatly advance understanding of the mechanisms underlying both the causes and consequences of glucocorticoid exposure during development. This information should prove vital to attempts to mitigate embryonic exposure and alleviate the long-term consequences of exposure.

描述（应用程序提供）：本申请提出了一个研究项目，该项目研究了胚胎发育期间经历的疾病在以后生活中易感性的机制。不良产前疾病与成年人的疾病患病率增加有关，这可能部分是由于胚胎暴露于孕妇糖皮质激素的增加而介导的。幸运的是，子宫核可以用作“代谢缓冲液”，并且能够将大部分的糖皮质激素（80-90％）从母体循环传播到胎儿循环时。不幸的是，几乎不可能检查出胚胎对增加的糖皮质激素的直接反应，因为糖皮质激素水平的变化也会改变孕产妇的生理学，这可能会间接影响胚胎发育。该提议利用了一种新型的禽类研究系统，即日本鹌鹑（Coturnix Japonica），在该系统中发生了胚胎发育，在孕产妇环境之外进行（i）胚胎如何调节胚胎暴露于孕产妇糖皮质激素，（ii）胚胎如何对增加葡萄糖糖苷暴露的疾病响应增加，以及（ii II）的长期曝光量增加了葡萄糖剂的长期影响。这项研究将检验以下假设：增加胚胎暴露于糖皮质激素会改变糖皮质激素对不良条件的反应，并导致终身对氧化应激，端粒缩短和后代存活的影响。使用LC/MS/MS来量化多种类固醇，将检查糖皮质激素暴露对胚胎内分泌环境的影响。纵向研究将用于表征糖皮质激素暴露增加对整个鸟类寿命的糖皮质激素产生，氧化应激和端粒动力学的影响。在该项目结束时，研究团队将确定胚胎调节其对主要衍生糖皮质激素的暴露的代谢途径，其特征是胚胎内分泌环境的反应，以响应增加糖皮质激素的暴露，并检查了这种暴露对生命长期压力的影响。这项工作的结果将大大提高人们对开发过程中糖皮质激素暴露的原因和后果的机制的理解。这些信息对于试图减轻胚胎暴露并减轻暴露的长期后果至关重要。

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）

In ovo metabolism and yolk glucocorticoid concentration interact to influence embryonic glucocorticoid exposure patterns.

卵内代谢和卵黄糖皮质激素浓度相互作用，影响胚胎糖皮质激素暴露模式。

DOI：
10.1016/j.ygcen.2018.11.013
发表时间：
2019
期刊：
General and comparative endocrinology
影响因子：
2.7
作者：
Vassallo,BrianG;Litwa,HannahP;Haussmann,MarkF;Paitz,RyanT
通讯作者：
Paitz,RyanT

The rate of telomere loss is related to maximum lifespan in birds.

DOI：
10.1098/rstb.2016.0445
发表时间：
2018-03-05
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
0
作者：
Tricola GM;Simons MJP;Atema E;Boughton RK;Brown JL;Dearborn DC;Divoky G;Eimes JA;Huntington CE;Kitaysky AS;Juola FA;Lank DB;Litwa HP;Mulder EGA;Nisbet ICT;Okanoya K;Safran RJ;Schoech SJ;Schreiber EA;Thompson PM;Verhulst S;Wheelwright NT;Winkler DW;Young R;Vleck CM;Haussmann MF
通讯作者：
Haussmann MF

Longevity and life history coevolve with oxidative stress in birds.

DOI：
10.1111/1365-2435.13228
发表时间：
2019-01
期刊：
Functional ecology
影响因子：
5.2
作者：
Vágási CI;Vincze O;Pătraș L;Osváth G;Pénzes J;Haussmann MF;Barta Z;Pap PL
通讯作者：
Pap PL

The response to stressors in adulthood depends on the interaction between prenatal exposure to glucocorticoids and environmental context.

DOI：
10.1038/s41598-023-33447-x
发表时间：
2023-04-15
期刊：
SCIENTIFIC REPORTS
影响因子：
4.6
作者：
Majer, Ariana D.;Paitz, Ryan T.;Tricola, Gianna M.;Geduldig, Jack E.;Litwa, Hannah P.;Farmer, Jenna L.;Prevelige, Brenna R.;McMahon, Elyse K.;McNeely, Taylor;Sisson, Zach R.;Frenz, Brian J.;Ziur, Alexis D.;Clay, Emily J.;Eames, Brad D.;McCollum, Shannon E.;Haussmann, Mark F.
通讯作者：
Haussmann, Mark F.

Maternal glucocorticoids promote offspring growth without inducing oxidative stress or shortening telomeres in wild red squirrels