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Updated: Aug 6, 2025

Using Ex Vivo Upright Droplet Cultures of Whole Fetal Organs to Study Developmental Processes during Mouse Organogenesis
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Using Ex Vivo Upright Droplet Cultures of Whole Fetal Organs to Study Developmental Processes during Mouse Organogenesis

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Testicular macrophages are recruited during a narrow fetal time window and promote organ-specific developmental

Xiaowei Gu1, Anna Heinrich1, Shu-Yun Li1

  • 1Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.

Nature Communications
|March 16, 2023
PubMed

Insights

This study reveals distinct origins and functions of testicular macrophages in mice. Yolk-sac-derived macrophages are early testicular cells, while hematopoietic stem cell-derived macrophages support adult functions like Leydig cell steroidogenesis.

Area of Science:

  • Reproductive biology
  • Immunology
  • Developmental biology

Background:

  • Macrophages play crucial roles in fetal testis development and function.
  • Two adult testicular macrophage populations, interstitial and peritubular, have been identified.
  • The hematopoietic origins and functional specialization of testicular macrophages remain debated.

Purpose of the Study:

  • To elucidate the developmental origins of testicular macrophages in mice.
  • To investigate the distinct functions of different macrophage populations in testicular development and adult function.
  • To clarify the roles of yolk-sac-derived versus hematopoietic stem cell (HSC)-derived macrophages.

Main Methods:

  • Hematopoietic lineage-tracing studies in mice.
  • Analysis of macrophage colonization during fetal gonad development.
  • Functional assays assessing macrophage roles in testis morphogenesis and Leydig cell steroidogenesis.

Main Results:

  • Yolk-sac-derived macrophages are the earliest testicular macrophages.
  • Fetal HSCs generate monocytes that differentiate into adult testicular macrophages in a Sertoli-cell-dependent manner.
  • Yolk-sac-derived and HSC-derived macrophages exhibit distinct functions during testis morphogenesis, and interstitial macrophages promote Leydig cell steroidogenesis.

Conclusions:

  • Testicular macrophages originate from both the yolk sac and fetal HSCs.
  • Distinct macrophage populations have specialized roles in testicular development and adult function.
  • Understanding these origins and functions provides insight into testicular health and disease.

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