Senescent cell number increases with age in different tissues, leading to greater senescent cell load, proinflammatory stress, and tissue dysfunction. In the current study, we tested the efficacy of senolytic drugs to reduce ovarian senescence and improve fertility in reproductive age female mice. In the first experiment, 1-month-old C57BL/6 female mice were treated every other week with D + Q (n = 24) or placebo (n = 24). At 3 and 6 months of age, female mice were mated with untreated males to evaluate pregnancy rate and litter size. In the second experiment, 6-month-old C57BL/6 female mice were treated monthly with D + Q (n = 30), fisetin (n = 30), or placebo (n = 30). Females were treated once a month until 11 months of age, then they were mated with untreated males for 30 days to evaluate pregnancy rate and litter size. In the first experiment, D + Q treatment did not affect pregnancy rate (P = 0.68), litter size (P = 0.58), or ovarian reserve (P > 0.05). Lipofuscin staining was lower in females treated with D + Q (P = 0.04), but expression of senescence genes in ovaries was similar. In the second experiment, D + Q or fisetin treatment also did not affect pregnancy rate (P = 0.37), litter size (P = 0.20), or ovarian reserve (P > 0.05). Lipofuscin staining (P = 0.008) and macrophage infiltration (P = 0.002) was lower in fisetin treated females. Overall, treatment with D + Q or fisetin did not affect ovarian reserve or fertility but did decrease some senescence markers in the ovary.

不同组织中的衰老细胞数量随着年龄的增长而增加，导致更大的衰老细胞负荷、促炎应激和组织功能障碍。在当前的研究中，我们测试了抗衰老药物在育龄雌性小鼠中减少卵巢衰老和提高生育能力的功效。在第一个实验中，1 个月大的 C57BL/6 雌性小鼠每隔一周接受一次 D + Q ( n  = 24) 或安慰剂 ( n  = 24) 治疗。在 3 个月和 6 个月大时，雌性小鼠与未经治疗的雄性小鼠交配，以评估妊娠率和产仔数。在第二个实验中，6 个月大的 C57BL/6 雌性小鼠每月接受 D + Q ( n  = 30)、非瑟酮 ( n  = 30) 或安慰剂 ( n = 30)治疗 。雌性每月接受一次治疗，直至 11 个月大，然后与未治疗的雄性交配 30 天，以评估妊娠率和产仔数。在第一个实验中，D + Q 治疗不影响妊娠率（P  = 0.68）、窝产仔数（P  = 0.58）或卵巢储备功能（P  > 0.05）。 D + Q 处理的雌性中脂褐质染色较低（P  = 0.04），但卵巢中衰老基因的表达相似。在第二个实验中，D + Q 或非瑟酮治疗也没有影响妊娠率（P  = 0.37）、窝产仔数（P  = 0.20）或卵巢储备功能（P  > 0.05）。经非瑟酮处理的雌性中，脂褐素染色（P  = 0.008）和巨噬细胞浸润（P  = 0.002）较低。总体而言，D + Q 或非瑟酮治疗不会影响卵巢储备或生育能力，但确实会降低卵巢中的一些衰老标志物。