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Published on: November 17, 2023
Generation, localization and functions of macrophages during the development of testis
Emmi Lokka1,2,3, Laura Lintukorpi1,2, Sheyla Cisneros-Montalvo1
1Institute of Biomedicine, University of Turku, Turku, FI-20520, Finland.
Abstract:
In the testis, interstitial macrophages are thought to be derived from the yolk sac during fetal development, and later replaced by bone marrow-derived macrophages. By contrast, the peritubular macrophages have been reported to emerge first in the postnatal testis and solely represent descendants of bone marrow-derived monocytes. Here, we define new monocyte and macrophage types in the fetal and postnatal testis using high-dimensional single-cell analyses. Our results show that interstitial macrophages have a dominant contribution from fetal liver-derived precursors, while peritubular macrophages are generated already at birth from embryonic precursors. We find that bone marrow-derived monocytes do not substantially contribute to the replenishment of the testicular macrophage pool even after systemic macrophage depletion. The presence of macrophages prenatally, but not postnatally, is necessary for normal spermatogenesis. Our multifaceted data thus challenge the current paradigms in testicular macrophage biology by delineating their differentiation, homeostasis and functions.
Insights
Testicular macrophages originate from fetal liver and embryonic precursors, not bone marrow. Prenatal macrophage presence is crucial for normal sperm production, challenging existing biology paradigms.
Area of Science:
- Reproductive Biology
- Immunology
- Cell Biology
Background:
- Current understanding suggests testicular macrophages originate from yolk sac and bone marrow.
- Peritubular macrophages are believed to arise postnatally solely from bone marrow-derived monocytes.
Purpose of the Study:
- To define novel monocyte and macrophage populations in the fetal and postnatal testis.
- To elucidate the origins and differentiation pathways of testicular macrophages.
- To investigate the role of testicular macrophages in spermatogenesis.
Main Methods:
- High-dimensional single-cell analyses were employed.
- Fetal and postnatal testicular tissues were analyzed.
- Macrophage depletion models were utilized.
Main Results:
- Interstitial macrophages predominantly originate from fetal liver precursors.
- Peritubular macrophages develop from embryonic precursors at birth.
- Bone marrow-derived monocytes do not significantly replenish testicular macrophages, even after depletion.
- Prenatal, but not postnatal, macrophage presence is essential for normal spermatogenesis.
Conclusions:
- This study redefines the origins and differentiation of testicular macrophages.
- It challenges established paradigms regarding testicular macrophage homeostasis and function.
- It highlights the critical role of prenatal macrophages in maintaining spermatogenesis.
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