The role of seasonal changes in light on the reproductive axis in female mice

光照季节变化对雌性小鼠生殖轴的作用

• 批准号: 10537542
• 负责人: Alexandra Marie Yaw
• 金额: $ 6.98万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-12 至 2023-08-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10537542
• 关键词: Automobile Driving; Behavior; Birth; Blood specimen; Breeding; Cues; Data; Diestrus; Endocrine; Environment; Estrus; Eye; Female; Fertility; Fertilization in Vitro; Follicle Stimulating Hormone; Foundations; Frequencies; Future; Goals; Gonadotropin Hormone Releasing Hormone; Hormones; Human; Hypothalamic structure; Individual; Infant Mortality; Injections; Laboratories; Light; Lighting; Lilium; Longitudinal Studies; Luteinizing Hormone; Measures; Mentors; Modernization; Morphology; Mus; Neurons; Neurosecretory Systems; Optic Nerve; Ovarian; Ovarian Follicle; Ovulation; Pathway interactions; Pattern; Periodicity; Photoperiod; Phototherapy; Physiology; Pituitary Gland; Pituitary Hormones; Play; Population; Protocols documentation; Reporter; Reproduction; Research; Research Personnel; Risk; Rodent; Rodent Model; Role; Signal Transduction; Therapeutic Intervention; Time; Training; Transgenic Organisms; Translating; Variant; Vasoactive Intestinal Peptide; Woman; Work; base; career; experience; experimental study; female fertility; implantation; improved; insight; light effects; light intensity; male; mortality; novel; novel strategies; offspring; oocyte quality; oocyte retrieval; pregnant; receptor expression; reproductive; reproductive axis; reproductive function; reproductive hormone; reproductive outcome; reproductive success; response; skills; steroid hormone; steroid hormone receptor; success; suprachiasmatic nucleus; therapeutic development

Project Summary In humans and laboratory rodents, there are seasonal patterns in birth and offspring mortality rates, reproductive hormone release, and in vitro fertilization success. It is unknown how female fertility is responding to time-of- year in non-seasonal breeders. Seasonal changes in lighting are characterized by high intensity long summer days and low intensity short winter days. Seasonal changes in light quality, notably light duration (photoperiod) and intensity, are candidate variables to drive the time-of year changes in female reproduction of non-seasonal breeders. As human and non-seasonal laboratory rodents do not exhibit breeding restricted to specific times of year, potential mechanisms by which variations in light quality, specifically photoperiod or light intensity, may modulate hormone release and ovarian function are unexamined. Photoperiod is the most salient and well- established cue signaling seasonal changes. However, with extensive artificial lighting, many modern-day humans do not experience seasonal changes in photoperiod, but do experience seasonal changes in light intensity. By increasing our understanding of how seasonally-modulated breeders adapt their physiology to light conditions, this project will lay the foundation necessary for the development of therapeutic interventions to improve reproduction during times of year when fertility and reproductive success are decreased. To demonstrate that the reproductive axis is modulated by photoperiod in non-seasonal mice, I established a longitudinal experimental protocol to collect serial blood samples from diestrus females on LD12:12 and long days (LD19:5) with indoor lighting intensity (300 Lux). I found that females on LD19:5 have reduced pulsatile release of luteinizing hormone (LH) and follicle stimulating hormone (FSH), two hormones required for ovarian function and fertility. The most direct pathway by which light influences LH and FSH is via a neuronal population expressing vasoactive intestinal peptide (VIP) of the suprachiasmatic nucleus. Light enters the eye and is transmitted to VIP neurons that project to gonadotropin releasing hormone (GnRH) neurons to modulate LH and FSH. Based on these data, I hypothesize that the VIP-GnRH-pituitary pathway adapts to changes in photoperiod and light intensity, with reduced functionality of this circuit on long days (LD19:5) and in bright intensity (1000 Lux) light, leading to reduced LH and FSH release patterns and reduced ovarian function compared to short (LD5:19) days and dim (50 lux) light. Aim 1 will determine the degree by which light intensity and photoperiod induce changes in LH and FSH release and ovarian function. Aim 2 will determine how VIP-GnRH-Pituitary connectivity and function adapt to photoperiod and light intensity. These studies will provide key insights into the neuronal mechanisms by which light qualities modulate hypothalamic and downstream endocrine pathways. The training from this proposal, with guidance from my Sponsors and mentoring committee, will prepare me for a successful career as an academic researcher investigating the role of light in modulating reproductive success.

项目概要 在人类和实验室啮齿动物中，出生率和后代死亡率、生殖率等存在季节性模式。 激素释放，体外受精成功。目前尚不清楚女性生育能力如何响应时间 非季节性饲养者的年份。光照季节变化的特点是高强度、长夏季 日和低强度短冬日。光质量的季节性变化，特别是光持续时间（光周期） 和强度，是驱动非季节性女性生殖一年中时间变化的候选变量 饲养员。由于人类和非季节性实验室啮齿动物不会表现出仅限于特定时间的繁殖 年，光质量（特别是光周期或光强度）变化的潜在机制可能 调节激素释放和卵巢功能未经检查。光周期是最显着和最有效的 建立了信号季节变化的线索。然而，由于大量的人工照明，许多现代 人类不会经历光周期的季节变化，但会经历光的季节变化 强度。通过增加我们对季节性调节饲养者如何调整其生理机能以适应光的了解 在条件允许的情况下，该项目将为开发治疗干预措施奠定必要的基础 在一年中生育率和繁殖成功率下降的时期改善繁殖。到 为了证明非季节性小鼠的生殖轴受到光周期的调节，我建立了一个 纵向实验方案，从 LD12:12 和长发情间期雌性中收集连续血液样本 天 (LD19:5)，室内照明强度 (300 Lux)。我发现 LD19:5 的雌性脉动减少了 黄体生成素 (LH) 和卵泡刺激素 (FSH) 的释放，这是卵巢所需的两种激素 功能和生育能力。光影响 LH 和 FSH 的最直接途径是通过神经元群 表达视交叉上核的血管活性肠肽（VIP）。光线进入眼睛并被 传输到 VIP 神经元，这些神经元投射到促性腺激素释放激素 (GnRH) 神经元以调节 LH 和 卵泡刺激素。根据这些数据，我假设 VIP-GnRH-垂体途径适应光周期的变化 和光强度，在长日照 (LD19:5) 和明亮强度 (1000 Lux）光，与短时间相比，导致 LH 和 FSH 释放模式减少，卵巢功能降低 (LD5:19) 天和昏暗 (50 勒克斯) 的光线。目标 1 将确定光强度和光周期的程度 诱导 LH 和 FSH 释放以及卵巢功能的变化。目标 2 将确定 VIP-GnRH-垂体如何 连接性和功能适应光周期和光强度。这些研究将为以下问题提供重要见解： 光质量调节下丘脑和下游内分泌途径的神经元机制。这 在我的发起人和指导委员会的指导下，根据该提案进行的培训将为我做好准备 作为一名学术研究人员，研究光在调节生殖成功中的作用，取得了成功的职业生涯。