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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.

本项目更新的总体目标是确定日常生活压力(即，