The circadian time of food intake and its effect on reproductive health

食物摄入的昼夜时间及其对生殖健康的影响

• 批准号: 10660026
• 负责人: Matthew P Butler
• 金额: $ 53.38万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10660026
• 关键词: Animal Model; Animals; Behavior; Biological Clocks; Biological Rhythm; Birth; Cell Nucleus; Chimera organism; Circadian Dysregulation; Circadian Rhythms; Competence; Consumption; Contraceptive methods; Cues; Darkness; Data; Desire for food; Eating; Energy Intake; Estradiol; Exposure to; Failure; Fasting; Female; Fertility; Food; GNRH1 gene; Goals; Health; Hormones; Hour; Human; Hypothalamic structure; Impairment; Jet Lag Syndrome; KISS1 gene; Laboratories; Lead; Light; Link; Low Birth Weight Infant; Luteinizing Hormone; Measures; Menstrual cycle; Metabolic; Mus; Mutant Strains Mice; Neurons; Outcome; Ovulation; Partner in relationship; Pathway interactions; Periodicity; Persons; Phase; Physiology; Population; Pre-Clinical Model; Premature Birth; Protocols documentation; Public Health; Quality of life; Reproduction; Reproductive Behavior; Reproductive Health; Reproductive Physiology; Resting Phase; Risk; Role; Running; Schedule; Sex Behavior; Sex Differences; Speed; Spontaneous abortion; System; Testing; Therapeutic Intervention; Time; Ventricular; Weight; circadian; circadian pacemaker; endometriosis; feeding; fitness; food consumption; food restriction; human model; in vivo; male; mating behavior; preference; reproductive; reproductive function; reproductive success; sex; shift work; social; success; tau mutation

Abstract Disruptions of the internal circadian clock system reduce reproductive success in both humans and animal models. For example, shift workers have greater rates of menstrual cycle disruption and endometriosis, reduced fertility, and have an increased risk for pre-term birth, low birth weight, and miscarriage. The mechanisms that contribute to this public health problem are unknown. We have focused on changes in when food is consumed, because circadian disruption often leads to abnormal food consumption during normal fasting phases. In a preclinical model, we have found that mis-timed meals reduce fertility in mice via an uncoupling of mating behavior and ovulation rhythms. In particular, in mice that eat during their rest phase, the pre-ovulatory luteinizing hormone (LH) surge that normally occurs at lights-off instead can occur at any time throughout the day. It is desynchronized from both the light-dark cycle and the feeding cycle. The timing of the LH surge is controlled proximately by a population of kisspeptin neurons that receive direct input from the circadian clock and that are sensitive to estradiol and metabolic cues. Our goals in this application are to identify specific mechanisms by which food-induced disruptions of central circadian clocks lead to impaired reproductive success. This will be accomplished in three aims. First, the relative sensitivity of male and female reproductive function to mis-timed food will be assessed. Second, we will determine how rhythmic light and food cues are integrated by an important ovulatory control system—kisspeptin neurons in the anteroventral periventricular nucleus. Finally, we will address the direct converse of our observation that a mismatch between the light-dark cycle and the circadian clock impairs reproduction. Namely, can appropriate food timing protect against circadian disruption and rescue reproductive competence? In addition, we will quantitatively assess the role of circadian clocks in kisspeptin neuronal function. The results of these studies will show how environmental cues and hypothalamic clocks interact in the control of fertility.

抽象的 昼夜节律内部时钟系统的破坏减少了人类和动物的生殖成功 型号。例如，转移工人的月经周期中断和子宫内膜异位症的发生率更高， 降低了生育能力，并增加了预期出生，低出生体重和流产的风险。 导致这个公共卫生问题的机制尚不清楚。我们专注于何时的变化 食物是消耗的，因为昼夜节律的干扰通常会导致正常情况下的食物异常 禁食阶段。在临床前模型中，我们发现错过的餐点通过 交配行为和排卵节奏的解偶联。特别是，在休息阶段进食的小鼠中 通常在灯光下发生的卵巢前叶酸马酮（LH）浪涌可能随时发生 整天。它是从浅黑暗循环和进食周期中进行的。时间的时机 LH激增受到接近亲吻肽神经元的控制，这些神经元直接从 昼夜节律对雌二醇和代谢线索敏感。我们在此应用中的目标是 确定食物引起的中央昼夜节律中断导致损害的特定机制 生殖成功。这将在三个目标中实现。首先，男性和女性的相对灵敏度 将评估对误以为食品的生殖功能。其次，我们将确定有节奏的光和 食物提示是由重要的排卵系统 - 前腹膜中的基氨基肽神经元整合的 周期性核。最后，我们将解决我们观察不匹配的直接交谈 在光线周期和昼夜节律之间会损害繁殖。即，可以适当的食物时机 防止昼夜节律破坏和救助复制能力？另外，我们将定量 评估昼夜节律时钟在Kisspeptin神经元功能中的作用。这些研究的结果将显示如何 环境线索和下丘脑时钟在控制能力方面相互作用。