Brown adipose tissue-derived exosomes delay fertility decline in aging mice

作者全名："Zhang, Hanke; Fang, Yuqing; Gao, Ying; Zeng, Xinliu; Lu, Zhenzhen; Liu, Lin; Chen, Chunyan; Huang, Jiayu; Li, Yanhui"

作者地址："[Zhang, Hanke; Fang, Yuqing; Gao, Ying; Zeng, Xinliu; Lu, Zhenzhen; Liu, Lin; Chen, Chunyan; Li, Yanhui] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Obstet & Gynecol, Wuhan, Peoples R China; [Huang, Jiayu] Chongqing Med Univ, Affiliated Hosp 1, Reprod Med Ctr, Chongqing, Peoples R China"

通信作者："Li, YH (通讯作者)，Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Obstet & Gynecol, Wuhan, Peoples R China.; Huang, JY (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Reprod Med Ctr, Chongqing, Peoples R China."

来源：FRONTIERS IN ENDOCRINOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001002960200001

JCR分区：Q2

影响因子：3.9

年份：2023

卷号：14

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：brown adipose tissue; exosome; ovarian aging; mitochondrial function; oocyte

摘要："IntroductionOvarian aging has steadily grown to be a significant health issue for women as a result of the increase in average life expectancy and the postponement of reproductive age. One of the important pathological foundations of ovarian aging is formed by mitochondrial dysfunction, which causes decreases in follicle quantity and oocyte quality. In recent years, brown adipose tissue (BAT) transplantation has been proven as an effective treatment for aging-related diseases, such as ovarian aging. However, BAT transplantation is an invasive operation with long-term risks. Therefore, we need to find an alternative strategy. MethodsWe injected BAT-derived exosomes into eight-month-old C57BL/6 female mice. The fertility was detected by the estrous cycle and mating test. The changes of ovary and oocyte were measured by ovarian volume, organ coefficient, follicle counting, and oocyte maturation rate. ROS level, mitochondrial membrane potential and ATP level were measured to analyze the mitochondrial function of oocytes. The changes in metabolism were explored by cold stimulation test, body weight and blood sugar. The possible molecular mechanism was further investigated by RNA sequencing. ResultsIn terms of fertility, the estrous cycle of aging mice after BAT-derived exosome intervention was more regular, and the number of progenies and litters was increased. At the tissue level, the ovaries in the BAT-exosome group were larger, and the number of primordial follicles, secondary follicles, antral follicles and total follicles increased. At the cellular level, BAT-derived exosomes improved the maturation of oocytes in vivo and in vitro, increased the mitochondrial membrane potential and ATP levels of oocytes, and decreased ROS levels. Besides, BAT-derived exosomes ameliorated the metabolism and viability of aging mice. Furthermore, mRNA sequencing showed that BAT exosomes altered the expression levels of genes related to metabolism and the quality of oocytes. ConclusionBAT-derived exosomes enhanced mitochondrial function, promoted follicle survival, improved fertility, and extended ovarian lifespan in aging mice."

基金机构："National Natural Science Foundation of China [82101711, 82201818]; cultivation fund of the First Affiliated Hospital of CQMU [PYJJ2022-04]"

基金资助正文："This research was supported by grants of the National Natural Science Foundation of China (No. 82101711, No. 82201818) and the cultivation fund of the First Affiliated Hospital of CQMU (No. PYJJ2022-04)."