Oxidative Stress, Hormones and Women s Health

氧化应激、激素和女性健康

• 批准号: 8553911
• 负责人: Enrique F. Schisterman
• 金额: $ 25.77万
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8553911
• 关键词: Accounting; Address; Aerobic; Affect; Aging; Alcohol consumption; All-Trans-Retinol; Animals; Antioxidants; Attention; Biochemical; Biological; Biological Markers; Birth Weight; Blood; Blood specimen; Body Fluids; Calendar; Cardiovascular Diseases; Carotene; Carotenoids; Cells; Chemicals; Chlamydia; Cholesterol; Chronic Disease; Clinic Visits; Cohort Studies; Conceptions; DNA; Data; Data Collection; Diet; Disease; Endometrium; Environment; Environmental Exposure; Estradiol; Estrogens; Evaluation; Exercise; F2-Isoprostanes; Failure; Female; Fertility; Free Radicals; Future; Goals; Gonadal Steroid Hormones; Growth and Development function; Health; Homocysteine; Homocystine; Hormonal; Hormones; Human; Individual; Infertility; Lead; Life; Lipid Peroxidation; Lipoprotein (a); Lipoproteins; Luteal Phase; Lutein; Luteinizing Hormone; Malignant Neoplasms; Measurement; Measures; Menstrual cycle; Menstruation; Methods; Micronutrients; Monitor; Nature; Outcome; Oxidants; Oxidative Stress; Paper; Participant; Phase; Physical activity; Plasma; Pregnancy; Premenopause; Preparation; Process; Production; Progesterone; Proteins; Publications; Reaction; Regulation; Research; Research Design; Research Personnel; Risk; Role; Sampling; Screening procedure; Serum; Spontaneous abortion; System; Testing; Time; Tissues; Tocopherols; Universities; Urine; Variant; Visit; Vitamins; Woman; Women' s Health; Work; aged; angiogenesis; base; cigarette smoking; clinical Diagnosis; cytokine; design; endometriosis; fasting glucose; follow-up; free radical oxygen; injured; interest; lycopene; men; neuronal cell body; oxidation; phthalates; phytoene; phytofluene; pregnant; proliferative phase Menstrual cycle; prospective; sample collection; zeaxanthin

As part of aerobic life, we oxidize a large pool of biomolecules to obtain chemical energy. During this process, several intermediates are formed; some are chemically unstable and are referred to as free radicals (FR). FR tend to react quickly with their surrounding biological environment; depending on the nature of the molecule attacked, different reactions can occur, i.e., lipid peroxidation, protein oxidation, or DNA oxidation products. As aerobic life has evolved, antioxidant defense systems against FR have developed. An imbalance between production of FR (oxidants) and defense systems against them (antioxidants) results in oxidative stress. This can lead to irreversible biochemical changes, with subsequent tissue damage and disease. Oxygen free radicals have been implicated in spontaneous abortions, infertility in men and women, reduced birth weight, aging and chronic disease processes, such as cardiovascular disease and cancer. While the mechanisms that relate oxidative stress with female fertility are not completely understood, recent animal and human studies have suggested that oxidative stress might have an important role in follicular growth, development of endometriosis, and regulation of angiogenesis in the endometrium. Micronutrient antioxidants, hormones and enzymatic antioxidants are able to neutralize oxygen free radicals and inhibit oxidation and, thereby, potentially reduce the risk of infertility. Numerous methods have been developed to measured lipid peroxidation products and lipid peroxidation damage in tissue, cell and body fluids. Markers of lipid peroxidation can be measured directly or by measuring any substance involved in the reaction process. Since radical species are the actual agents to injured cells, their direct measurement would be preferable for clinical diagnosis. However, radical species disappear rapidly yielding stable primary and secondary lipid peroxidation products. Although, lipid peroxidation has been related to many health outcomes, there still is large disagreement between investigators on which method should be use to evaluate circulating levels of lipid peroxidation making it difficult to synthesize research findings. Recently, it has been demonstrated that plasma lipoprotein levels fluctuate during the course of the menstrual cycle. This cyclic fluctuation in lipoproteins has been associated with fluctuation in plasma antioxidant concentrations . Hormones, lipoproteins, a-tocopherol and carotenoids were measured simultaneously for 2-3 consecutive days in each phase of the menstrual cycle for 12 healthy women. Carotenoids were lowest during menses, with concentrations of lutein/zeaxanthin and its metabolite, anhydrolutein, higher at all three phases (early follicular, late follicular and luteal) than during menses. Plasma -carotene peaked in the late follicular phase, whereas plasma lycopene, phytoene, phytofluene and retinol concentrations peaked in the luteal phase. Circulating levels of estradiol and progesterone have also been shown to fluctuate during the follicular and luteal phase of the menstrual cycle in ovulatory women. Estrogen is a powerful antioxidant that affects oxidative stress and homocysteine levels in women. However, little is known about the relation between oxidative stress, estrogen levels and their influence on outcomes such as likelihood of conception or spontaneous abortions. Prior to evaluating this relation, it is critical to have standardized measurements of oxidative stress and to know they vary with hormone levels. The primary goals of this study are to better understand the intricate relationship between hormone levels and oxidative stress during the menstrual cycle (i.e. estrogen, progesterone, LH, etc). More specifically, we would study: (i) the intra-cycle variation of oxidative stress; (ii) the relation between hormone levels and oxidative stress during the menstrual cycle in pre-menopauusal women; and (iii) influence of external factors such as cigarette smoking, alcohol consumption, and exercise on oxidative stress and hormone levels. Study Design: A prospective longitudinal cohort study of 250 women is being conducted in a university setting. Screening tests are performed on participating individuals to exclude women who are pregnant and or have asymptomatic chlamydia. The recruitment period will last up to one full calendar year to account for seasonal variability. The participants are being followed for 2 menstrual cycles from day 1 of the menstrual cycle to the end, taking blood and urine samples at intervals consistent with hormonal fluctuations. At each of these visits data will be collected on diet, physical activity and other environmental exposures. Urine and blood samples will be evaluated for levels of F2 isoprostanes and subproducts, conjugate dianes, fasting glucose, total cholesterol and subproducts, and serum antioxidant vitamins. Public Heath Significance: This study will elucidate the best methods to estimate oxidative stress in premenopausal women and to better understand the relation between oxidative stress and menstrual function. This study will also provide basic reference data for future studies examining the role of oxidative stress in fertility, risk of spontaneous abortion, and other pregnancy related outcomes.

作为有氧寿命的一部分，我们将大量的生物分子氧化以获得化学能。在此过程中，形成了几个中间体。有些在化学上不稳定，被称为自由基（FR）。 FR倾向于与周围的生物环境迅速反应。根据攻击的分子的性质，可能发生不同的反应，即脂质过氧化，蛋白质氧化或DNA氧化产物。随着有氧寿命的发展，针对FR的抗氧化防御系统已经发展出来。 FR（氧化剂）的产生与防御系统（抗氧化剂）之间的不平衡导致氧化应激。这可能会导致不可逆转的生化变化，随后发生组织损伤和疾病。 氧气自由基与自发流产，男性和女性的不育症有关，出生体重减轻，衰老和慢性病过程，例如心血管疾病和癌症。尽管尚未完全了解将氧化应激与女性生育能力相关的机制，但最近的动物和人类研究表明，氧化应激可能在卵泡生长，子宫内膜异位症的发展以及子宫内膜中血管生成的调节中具有重要作用。微量营养素抗氧化剂，激素和酶抗氧化剂能够中和氧自由基并抑制氧化，从而有可能降低不孕症的风险。 已经开发了许多方法来测量组织，细胞和体液中的脂质过氧化产物和脂质过氧化损伤。可以直接测量脂质过氧化的标志物，也可以通过测量反应过程中涉及的任何物质。由于自由基物种是受伤细胞的实际药物，因此可以直接测量临床诊断。然而，自由基物种迅速消失，产生稳定的原发性和二级脂质过氧化产物。尽管脂质过氧化与许多健康结果有关，但研究者之间仍然存在很大的分歧，该方法应使用哪种方法来评估循环水平的脂质过氧化水平，从而难以合成研究结果。 最近，已经证明血浆脂蛋白水平在月经周期过程中波动。脂蛋白中的这种环状波动与血浆抗氧化剂浓度的波动有关。在月经周期的每个阶段，对12名健康女性的每个阶段的每个阶段，同时测量激素，脂蛋白，A-生育酚和类胡萝卜素。类胡萝卜素在月经期间最低，其浓度为叶黄素/玉米黄质及其代谢产物，赤霉素蛋白，在所有三个阶段（早期卵泡，晚卵泡和黄体）都比月经更高。血浆 - 芳香烯在晚期卵泡期达到峰值，而血浆番茄红素，植物二苯乙烯，植物氟苯和视黄醇浓度在黄体期达到峰值。 在产卵女性的月经周期的卵泡和黄体期间，雌二醇和孕酮的循环水平也被证明会波动。雌激素是一种强大的抗氧化剂，会影响女性的氧化应激和同型半胱氨酸水平。然而，关于氧化应激，雌激素水平及其对诸如构思或自发堕胎可能性之类的结果的影响之间的关系知之甚少。 在评估这种关系之前，必须对氧化应激进行标准化的测量并知道它们随激素水平变化至关重要。 这项研究的主要目标是更好地了解月经周期中激素水平与氧化应激之间的复杂关系（即雌激素，孕酮，LH等）。更具体地说，我们将研究：（i）氧化应激的周期内变化； （ii）在月经前妇女的月经周期中激素水平与氧化应激之间的关系； （iii）外部因素的影响，例如吸烟，饮酒和运动对氧化应激和激素水平的影响。 研究设计：在大学环境中，正在对250名女性进行一项前瞻性纵向队列研究。对参与的人进行筛查测试，以排除怀孕或无症状衣原体的妇女。招聘期限将持续到一个完整的日历年，以解释季节性变异性。从月经周期的第1天到结束，参与者进行了2个月经周期，以与激素波动一致的间隔采集血液和尿液样本。这些访问中的每一个都将收集有关饮食，体育锻炼和其他环境暴露的数据。 将评估尿液和血液样本的F2异丙烷和亚产物，结合Dianes，禁食葡萄糖，总胆固醇和亚产物以及血清抗氧化剂维生素的水平。 公共卫生意义：这项研究将阐明估计绝经前女性氧化应激的最佳方法，并更好地了解氧化应激与月经功能之间的关系。这项研究还将为未来的研究提供基本参考数据，以研究氧化应激在生育能力，自发流产的风险以及其他与妊娠相关的结果中的作用。