Progression of uterine aging in mice

Reproductive decline with advanced maternal age is majorly driven by functional changes to the uterus in mice. Here, we conducted an aging time course series in female mice and assessed changes to the uterine transcriptomes between young females and those aged between 24 weeks and 52 weeks and over. We also assessed the impact of key candidates of aging driver genes in the human endometrial Ishikawa cell line. Our results show an increase in transcriptional heterogeneity in the uterus as a function of maternal age. However, these changes are largely distinct from organismal aging and highlight that aging of reproductive tissues, notably the endometrium, is driven by a unique set of aging driver genes. RNA-seq profiling of 1) E3.5 dpc whole tissue intact uteri was obtained from young and aged virgin wild-type C57BL/6 mice that were mated with vasectomized wild-type males; and 2) endometrial epithelial organoids obtained from young and aged non-mated virgin wild-type C57BL/6 mice. All collected samples were processed for RNA-sequencing analysis.