EFFECTS OF COMMON LIFE STRESSES ON FERTILITY

共同生活压力对生育力的影响

基本信息

批准号：
8125587
负责人：
JUDY L CAMERON
金额：
$ 6.69万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8125587
关键词：
Address Amenorrhea Animals Anxiety Behavior Brain Butyric Acids Cells Characteristics Chronic Clinic Corticotropin-Releasing Hormone Diet Embryonic Development Endorphins Estradiol Female Fertility Functional disorder Gene Expression Goals Grant Heart Rate Homogeneously Staining Region Hour Housing Hypothalamic structure Impairment In Situ Hybridization In Vitro Individual Individual Differences Infertility Intake Life Stress Luteal Phase Macaca fascicularis Maintenance Menstrual cycle Messenger RNA Metabolic stress Moderate Exercise Monkeys Monoamine Oxidase A Monoamine Oxidase B Neurons Norepinephrine Oocytes Ovarian Ovarian Steroid Hormone Ovary Pathway interactions Pattern Periodicity Pharmaceutical Preparations Physiological Pregnancy Rate Pro-Opiomelanocortin Progesterone Psychological Stress Psychosocial Stress Regimen Research Running Selective Serotonin Reuptake Inhibitor Serotonin Stress System Testing Tryptophan 5-monooxygenase Tyrosine 3-Monooxygenase Woman base design diet and exercise experience gamma-Endorphin granulosa cell improved in vivo neural circuit neuromechanism neuropeptide Y noradrenergic oocyte maturation prevent proliferative phase Menstrual cycle raphe nuclei receptor relating to nervous system reproductive reproductive axis reproductive function reproductive hormone research study response serotonin transporter stress resilience trend

项目摘要

The overall goal of this project renewal is to determine the mechanisms by which common life stresses (i.e., dieting, moderate exercise and psychological stress) impair activity of the reproductive axis and fertility. Female cynomolgus monkeys, which like women have 28-day menstrual cycles throughout the year, show individual differences in responsiveness to stress, with stress-sensitive animals rapidly developing stressinduced reproductive dysfunction, medium stress-resilient animals developing stress-induced reproductive dysfunction after sustained stress exposure, and highly stress-resilient animals maintaining normal menstrual cyclicity throughout stress exposure. Interestingly, all monkeys show a significant impairment of fertility with stress exposure. The stress used for these studies is patterned after that documented in women with Hypothalamic Amenorrhea, who generally experience increased psychosocial stress combined with a mild metabolic stress (resulting from dieting and exercise). Monkeys are exposed to a combination of mild psychosocial stress (moving monkeys to a new housing room) + a moderate diet (20% decrease in calorie intake) + moderate exercise (running at a moderate pace for 1 hour, 5 days a week). We identified several stable characteristics associated with stress-sensitivity: lower follicular phase estradiol secretion, lower luteal phase progesterone secretion, higher heart rate, increased anxious behavior, lower activity of the brain serotonin system, and increased gene expression in hypothalamic GABAergic neurons. Our findings suggest that common life stresses have a more significant impact on both circulating levels of reproductive hormones and fertility than previously appreciated, particularly in stress-sensitive individuals. The specific aims of this renewal are: (1) to determine whether increasing brain serotonin levels by chronic treatment with a serotonin reuptake inhibitor (SSRI; a common anti-anxiety medication) will improve stress resilience, (2) identify further differences in neural circuits in stress-sensitive versus stress-resilient individuals, and (3) determine whether stress exposure has a negative impact at the level of the ovary on oocyte viability, early embryo development and ovarian cell steroidogenic capacity. The proposed studies will further our understanding of how common life stresses impact reproductive function, with the long-term goal of developing new treatments to make stress-sensitive individuals more stress resilient.

该项目更新的总体目标是确定共同生活压力的机制（即，节食、适度运动和心理压力）会损害生殖轴的活动和生育能力。雌性食蟹猴与女性一样，全年有 28 天的月经周期，对压力反应的个体差异，压力敏感的动物迅速发展为压力诱发生殖功能障碍，中等应激恢复能力的动物出现应激诱导的生殖持续应激暴露后功能障碍，以及高度应激恢复的动物保持正常整个压力暴露过程中的月经周期。有趣的是，所有猴子都表现出显着的生育力与压力暴露。这些研究中使用的压力是根据女性记录的压力模式设计的患有下丘脑性闭经的人，通常会经历社会心理压力增加以及轻度代谢压力（由节食和锻炼引起）。猴子暴露在温和的环境中心理社会压力（将猴子搬到新的房间）+适度饮食（卡路里减少20% 摄入量）+适度运动（每周 5 天，中等配速跑步 1 小时）。我们确定了几个与压力敏感性相关的稳定特征：卵泡期雌二醇分泌较低、黄体较低阶段黄体酮分泌，心率加快，焦虑行为增加，大脑活动降低血清素系统，并增加下丘脑 GABA 能神经元的基因表达。我们的发现表明共同的生活压力对生殖循环水平有更显着的影响荷尔蒙和生育能力比以前认识的要大，特别是对于压力敏感的个体。具体的此次更新的目的是：（1）确定长期治疗是否可以增加大脑血清素水平血清素再摄取抑制剂（SSRI；一种常见的抗焦虑药物）将提高压力恢复能力，(2) 确定压力敏感个体与压力复原个体的神经回路的进一步差异，以及（3）尽早确定压力暴露是否对卵巢水平的卵母细胞活力产生负面影响胚胎发育和卵巢细胞类固醇生成能力。拟议的研究将进一步推动我们了解常见的生活压力如何影响生殖功能，长期目标是开发新的治疗方法，使压力敏感的人更具压力恢复能力。