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

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/9022970
• 关键词: Address; Adult; Adverse event; Affect; Aging; Biomedical Research; Birds; Birth; Blood Circulation; Buffers; Chronic Disease; Chronic stress; Corticosterone; Coturnix japonica; Development; Disease; Disease susceptibility; Dose; Embryo; Embryonic Development; Endocrine; Environment; Enzymes; Exposure to; Fetal Development; Fetal Growth Retardation; Fetoplacental Circulation; Funding; Glucocorticoids; Goals; Gonadal Steroid Hormones; Grant; Health; Hormones; Hydroxysteroid Dehydrogenases; Incidence; Individual; Life; Link; Long-Term Effects; Longevity; Longitudinal Studies; Low Birth Weight Infant; Maternal Physiology; Mediating; Metabolic; Metabolic Pathway; Metabolism; Mothers; Oviparity; Oxidative Stress; Physiological; Placenta; Plant Roots; Play; Prevalence; Process; Production; Program Development; Research; Research Project Grants; Role; Science; Signal Transduction; Steroids; Stress; Students; Substance abuse problem; System; Telomere Shortening; Testing; Training; Universities; Work; base; design; egg; enzyme deficiency; experience; fetal; fetal programming; hypothalamic-pituitary-adrenal axis; liquid chromatography mass spectrometry; maternal stress; meetings; neuropsychological; novel; nutrition; offspring; placental mammal; prenatal; prenatal stress; programs; psychological distress; public health relevance; response; telomere; undergraduate student

 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（由申请人提供）：本申请提出了一个研究项目，调查胚胎发育期间经历的条件影响以后生活中疾病易感性的机制。不良的产前条件与成人疾病患病率增加有关，这可能部分是由于胚胎暴露于母体糖皮质激素增加所致。幸运的是，胎盘作为一个“代谢缓冲器”，它能够代谢大部分糖皮质激素（80- 90%），因为它们从母体循环到胎儿循环。不幸的是，几乎不可能检查发育中的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母体生理，这可能间接影响胚胎发育。该提案利用了一种新的鸟类研究系统，日本鹌鹑（Coturnix japonica），其中胚胎发育发生在母体环境之外，以检查（i）胚胎如何调节母体糖皮质激素的暴露，（ii）胚胎如何对糖皮质激素暴露增加做出反应，以及（iii）糖皮质激素暴露增加的长期影响。这项研究将测试这一假设，即增加胚胎暴露于糖皮质激素改变糖皮质激素对不利条件的反应，并导致终身影响氧化应激，端粒缩短，后代的生存。使用LC/MS/MS来量化广泛的类固醇，将检查糖皮质激素暴露增加对胚胎内分泌环境的影响。纵向研究将被用来描述增加糖皮质激素暴露对糖皮质激素产生，氧化应激和端粒动态在整个鸟类寿命的影响。在该项目结束时，研究小组将确定胚胎调节其暴露于母体来源的糖皮质激素的代谢途径，表征胚胎内分泌环境对糖皮质激素暴露增加的反应，并检查这种暴露对终身压力的后果。从这项工作的结果将大大推进了解的机制的原因和糖皮质激素暴露在发展过程中的后果。这一信息对于减轻胚胎接触和减轻接触的长期后果的努力至关重要。

项目成果

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.

端粒损失率与鸟类的最大寿命有关。

• 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
• 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.

Oxytocin prevents dysregulation of the acute stress response and glucocorticoid-induced oxidative stress in chronically isolated prairie voles.

催产素可防止长期隔离的草原田鼠急性应激反应和糖皮质激素诱导的氧化应激的失调。

• DOI: 10.1016/j.psyneuen.2023.106121
• 发表时间: 2023
• 期刊: Psychoneuroendocrinology
• 影响因子: 3.7
• 作者: Stevenson,JennieR;McMahon,ElyseK;McNeely,TaylorL;Haussmann,MarkF
• 通讯作者: Haussmann,MarkF