Single xenotransplant of rat brown adipose tissue prolonged the ovarian lifespan of aging mice by improving follicle survival
Single xenotransplant of rat brown adipose tissue prolonged the ovarian lifespan of aging mice by improving follicle survival
复制标题
大鼠棕色脂肪组织的单次异种移植通过提高卵泡存活率延长了衰老小鼠的卵巢寿命
DOI：
10.1111/acel.13024
复制
发表时间：
2019-08-06
期刊：
影响因子：
7.8
通讯作者：
Zhang, Dong
中科院分区：
文献类型：
--
作者：
Chen, Liang-Jian;Yang, Zhi-Xia;Zhang, Dong
延长卵巢寿命是有吸引力和挑战性的。最佳的临床策略必须是安全、长效、简单和经济的。棕色脂肪组织（BAT），这是最丰富和强大的婴儿，同种异体移植已被用于治疗各种人类疾病的小鼠模型。我们能用BAT来延长衰老小鼠的卵巢寿命吗？由于缺乏自愿的婴儿供体，我们能否尝试BAT异种移植来缓解临床对同种异体BAT的需求？在目前的研究中，我们发现单次大鼠到小鼠（RTM）BAT异种移植不会引起全身免疫排斥反应，但确实显著提高了小鼠的生育能力，并且有效期超过5个月（相当于人类10年）。接下来，我们进行了一系列分析，包括卵泡计数; AMH水平;发情周期; mTOR活性; GDF 9，BMP 15，LHR，Sirt 1和Cyp 19 a水平; ROS和annexin V水平; IL 6和脂联素水平;生化血液指标;体温;转录组;和DNA甲基化研究。由此，我们提出大鼠BAT异种移植挽救了指示卵泡和卵母细胞质量的多个指标;大鼠BAT还改善了衰老小鼠的代谢和总体健康状况;并且转录和表观遗传学改变了小鼠的发育。F0代小鼠DNA甲基化水平的提高可使F1代小鼠受益;以及多个KEGG通路和GO分类的生物过程中的差异表达基因（DEG）或差异甲基化区域（DMR），F0和F1之间所涉及的相同。本研究可为临床近缘人BAT异种移植提供参考。
Prolonging the ovarian lifespan is attractive and challenging. An optimal clinical strategy must be safe, long-acting, simple, and economical. Allotransplantation of brown adipose tissue (BAT), which is most abundant and robust in infants, has been utilized to treat various mouse models of human disease. Could we use BAT to prolong the ovarian lifespan of aging mice? Could we try BAT xenotransplantation to alleviate the clinical need for allogeneic BAT due to the lack of voluntary infant donors? In the current study, we found that a single rat-to-mouse (RTM) BAT xenotransplantation did not cause systemic immune rejection but did significantly increase the fertility of mice and was effective for more than 5 months (equivalent to 10 years in humans). Next, we did a series of analysis including follicle counting; AMH level; estrous cycle; mTOR activity; GDF9, BMP15, LHR, Sirt1, and Cyp19a level; ROS and annexin V level; IL6 and adiponectin level; biochemical blood indices; body temperature; transcriptome; and DNA methylation studies. From these, we proposed that rat BAT xenotransplantation rescued multiple indices indicative of follicle and oocyte quality; rat BAT also improved the metabolism and general health of the aging mice; and transcriptional and epigenetic (DNA methylation) improvement in F0 mice could benefit F1 mice; and multiple KEGG pathways and GO classified biological processes the differentially expressed genes (DEGs) or differentially methylated regions (DMRs) involved were identical between F0 and F1. This study could be a helpful reference for clinical BAT xenotransplantation from close human relatives to the woman.