Human in vitro spermatogenesis as a regenerative therapy - where do we stand?

Nat Rev Urol. 2023 Aug;20(8):461-479. doi: 10.1038/s41585-023-00723-4. Epub 2023 Feb 7.


Spermatogenesis involves precise temporal and spatial gene expression and cell signalling to reach a coordinated balance between self-renewal and differentiation of spermatogonial stem cells through various germ cell states including mitosis, and meiosis I and II, which result in the generation of haploid cells with a unique genetic identity. Subsequently, these round spermatids undergo a series of morphological changes to shed excess cytoplast, develop a midpiece and tail, and undergo DNA repackaging to eventually form millions of spermatozoa. The goal of recreating this process in vitro has been pursued since the 1920s as a tool to treat male factor infertility in patients with azoospermia. Continued advances in reproductive bioengineering led to successful generation of mature, functional sperm in mice and, in the past 3 years, in humans. Multiple approaches to study human in vitro spermatogenesis have been proposed, but technical and ethical obstacles have limited the ability to complete spermiogenesis, and further work is needed to establish a robust culture system for clinical application.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Male
  • Mice
  • Semen*
  • Spermatids / metabolism
  • Spermatogenesis*
  • Spermatozoa / metabolism