Photoperiod, melatonin, and reproductive aging

光周期、褪黑激素和生殖衰老

• 批准号: 7094416
• 负责人: NED J PLACE
• 金额: $ 14.65万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-21 至 2009-07-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7094416
• 关键词: aging; cell age; cell senescence; cytogenetics; developmental genetics; estrogen receptors; female reproductive system; fertility; graafian follicles; hamsters; histology; hormone regulation /control mechanism; melatonin; organ culture; ovary; ovary disorder; photostimulus; reproductive development; telomere; tissue /cell culture; uterus disorder

DESCRIPTION (provided by applicant): This proposal outlines a career development plan for the applicant, a clinically trained obstetrician/gynecologist, who is making the transition from clinician to basic biomedical researcher. The candidate's goals for this award are to learn modern molecular and cellular techniques as applied to his research on female reproductive aging, and to facilitate the final transition to becoming an independent investigator. Under the mentorship of established investigators and a multidisciplinary advisory committee, the candidate will pursue a program of instruction and research that maximizes the likelihood of his developing into an independent scientist. The research proposed seeks to determine how photoperiod and the pineal gland hormone melatonin affect female reproductive aging. The model species is the Siberian hamster (Phodopus sungorus), an easily maintained laboratory animal whose reproductive biology is exquisitely sensitive to day length and melatonin. Rearing female hamsters in a short day photoperiod decelerates reproductive aging. Short day females had significantly greater litter success than age-matched long day females at 9 months of age. Pregnancy failures occurred only in long day females, and maternal and fetal deaths during parturition in this group are consistent with uterine dysfunction. Ovaries from adult short day females had twice as many primordial follicles as ovaries from age-matched long day females. Three aims are proposed: 1) to determine if the photoperiodic effect on ovarian primordial follicle number is due to a decrease in follicular atresia and/or an increase in follicular renewal; 2) to identify how the hormones and factors that modulate primordial follicle activation are affected by photoperiod and melatonin; and 3) to determine if photoperiod and melatonin modulate the age-associated decline in uterine function by inhibiting cellular senescence, telomere shortening, and attrition of estrogen receptors. The proposed work is relevant to understanding the cellular and molecular mechanisms underlying reproductive aging, and how that process may be decelerated. Once the objectives of this award have been met, the candidate will work as an independent investigator, and carry out research on reproductive aging that is truly integrative.

描述（由申请人提供）：本提案概述了申请人的职业发展计划，申请人是一名经过临床培训的产科医生/妇科医生，正在从临床医生过渡到基础生物医学研究人员。该奖项的候选人的目标是学习现代分子和细胞技术，应用于他对女性生殖衰老的研究，并促进最终过渡到成为一名独立的研究者。在既定调查人员和多学科咨询委员会的指导下，候选人将追求一个教学和研究计划，最大限度地提高他发展成为独立科学家的可能性。这项研究旨在确定光周期和松果体激素褪黑激素如何影响女性生殖衰老。模型物种是西伯利亚仓鼠（Photopus sungorus），一种易于维持的实验室动物，其生殖生物学对日照长度和褪黑激素非常敏感。在短日照条件下饲养雌性仓鼠可以延缓生殖衰老。在9个月龄时，短日照雌性的产仔成功率显著高于年龄匹配的长日照雌性。妊娠失败仅发生在长日女性中，该组分娩期间的孕产妇和胎儿死亡与子宫功能障碍一致。成年短日照雌性的卵巢中原始卵泡数量是年龄匹配的长日照雌性卵巢的两倍。提出了三个目标：1）确定光周期对卵巢原始卵泡数量的影响是否是由于卵泡闭锁的减少和/或卵泡更新的增加; 2）确定调节原始卵泡激活的激素和因子如何受到光周期和褪黑激素的影响;和3）确定光周期和褪黑激素是否通过抑制细胞衰老来调节与年龄相关的子宫功能下降，端粒缩短和雌激素受体的损耗。拟议的工作与理解生殖衰老的细胞和分子机制以及如何减缓这一过程有关。一旦这个奖项的目标已经实现，候选人将作为一个独立的调查员工作，并进行生殖老化的研究是真正的综合。