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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

基本信息

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
项目类别：
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

项目摘要

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.

摘要