Cell Death and Disease (May 2021)

The essential roles of M ps 1 in spermatogenesis and fertility in mice

  • Qiang Fang,
  • Xue-Lin Chen,
  • Lei Zhang,
  • Ya-Bin Li,
  • Tian-Zeng Sun,
  • Chen-Xin Yang,
  • Jian-Feng Chang,
  • Xiao-Mei Yang,
  • Feng Sun

DOI
https://doi.org/10.1038/s41419-021-03815-4
Journal volume & issue
Vol. 12, no. 6
pp. 1 – 13

Abstract

Read online

Abstract Monopolar spindle 1 (MPS1), which plays a critical role in somatic mitosis, has also been revealed to be essential for meiosis I in oocytes. Spermatogenesis is an important process involving successive mitosis and meiosis, but the function of MPS1 in spermatogenesis remains unclear. Here, we generated Mps1 conditional knockout mice and found that Ddx4-cre-driven loss of Mps1 in male mice resulted in depletion of undifferentiated spermatogonial cells and subsequently of differentiated spermatogonia and spermatocytes. In addition, Stra8-cre-driven ablation of Mps1 in male mice led to germ cell loss and fertility reduction. Spermatocytes lacking M ps 1 have blocked at the zygotene-to-pachytene transition in the prophase of meiosis I, which may be due to decreased H2B ubiquitination level mediated by MDM2. And the expression of many meiotic genes was decreased, while that of apoptotic genes was increased. Moreover, we also detected increased apoptosis in spermatocytes with Mps1 knockout, which may have been the reason why germ cells were lost. Taken together, our findings indicate that MPS1 is required for mitosis of gonocytes and spermatogonia, differentiation of undifferentiated spermatogonia, and progression of meiosis I in spermatocytes.