Physiological premature aging of ovarian blood vessels leads to decline in fertility in middle-aged mice

Ovarian function declines significantly as females enter middle-age, but the mechanisms underlying this decline remain unclear. Here, we utilize whole-organ imaging to observe a notable decrease in ovarian blood vessel (oBV) density and angiogenesis intensity of middle-aged mice. This leads to a diminished blood supply to the ovaries, resulting in inadequate development and maturation of ovarian follicles. Utilizing genetic-modified mouse models, we demonstrate that granulosa cell secreted VEGFA governs ovarian angiogenesis, but the physiological decline in oBV is not attributed to VEGFA insufficiency. Instead, through single-cell sequencing, we identify the aging of the ovarian vascular endothelium as the…

• NN
  National Natural Science Foundation of China

  Award: 82230051
• CA
  China Agricultural University

  Award: 1021-00109035
• TU
  Tsinghua University
• TU
  Taizhou University
• NK
  National Key Research and Development Program of China

  Awards: 2022YFC2703803, 82230051