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Updated: Sep 20, 2025

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Mouse-human species differences in early testicular development and its implications.

Gerald R Cunha1, Mei Cao1, Sena Aksel1

  • 1Department of Urology, University of California, 400 Parnassus Avenue, San Francisco, CA, 94143, USA.

Differentiation; Research in Biological Diversity
|June 6, 2022
PubMed
Summary

Mouse models offer insights into human organogenesis, but significant differences exist in testicular development. This study highlights key distinctions in early human and mouse testis formation, particularly regarding cell origins and medullary development.

Keywords:
Androgen receptorLeydig cellsPeritubular myoid cellsSertoli cellsTestis

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Area of Science:

  • Comparative developmental biology
  • Reproductive medicine
  • Organogenesis

Background:

  • Mouse models are widely used for human organogenesis, yet significant anatomical, morphogenetic, and molecular differences exist, particularly in testicular development.
  • Existing literature lacks detailed ontogeny of mouse testicular development and comprehensive data on human testicular development.
  • Meaningful comparison between mouse and human testicular development is hindered by these knowledge gaps.

Approach:

  • Histologic and immunohistochemical studies were conducted on comparable stages of mouse and human testicular development.
  • Focused on the differentiation and origins of Leydig, Sertoli, and myoid cells.
  • Included a review of existing literature and new observational data.

Key Points:

  • Developing human testes exhibit an androgen-receptor-positive testicular medulla, absent in developing mouse testes.
  • The human testicular medulla and mesonephros are implicated as a source of Sertoli cells, showing mesenchymal-to-epithelial transition.
  • Sertoli (SOX9) and Leydig (HSD3B1) cell markers are not found in the coelomic zone of developing human testes, unlike proposed origins in mice.

Conclusions:

  • Significant differences exist in early human and mouse testicular development, challenging direct translatability of mouse models.
  • The origin of myoid cells in both species remains undetermined.
  • This study provides a detailed comparative analysis of early testicular development, emphasizing species-specific processes.