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

Abstract

A growing body of evidence demonstrates that fetal-derived tissue-resident macrophages have developmental functions. It has been proposed that macrophages promote testicular functions, but which macrophage populations are involved is unclear. Previous studies showed that macrophages play critical roles in fetal testis morphogenesis and described two adult testicular macrophage populations, interstitial and peritubular. There has been debate regarding the hematopoietic origins of testicular macrophages and whether distinct macrophage populations promote specific testicular functions. Here our hematopoietic lineage-tracing studies in mice show that yolk-sac-derived macrophages comprise the earliest testicular macrophages, while fetal hematopoietic stem cells (HSCs) generate monocytes that colonize the gonad during a narrow time window in a Sertoli-cell-dependent manner and differentiate into adult testicular macrophages. Finally, we show that yolk-sac-derived versus HSC-derived macrophages have distinct functions during testis morphogenesis, while interstitial macrophages specifically promote adult Leydig cell steroidogenesis. Our findings provide insight into testicular macrophage origins and their tissue-specific roles.

Lats1 and Lats2 regulate YAP and TAZ activity to control the development of mouse Sertoli cells

“…Sertoli cells were recently shown to be responsible for the colonization of the gonad by monocytes, which subsequently differentiate into macrophages. 85 Since Cyr61 is expressed in the developing Sertoli cells, 22 it would be interesting to determine if low basal activity of YAP/TAZ in Sertoli cells normally contributes to the recruitment of immune cells to the gonad.…”

“…However, it was previously shown that CYR61 acts a key macrophage chemoattractant in the liver and that its secretion can be induced by YAP/TAZ in hepatocytes, 84 suggesting that the increase in YAP/TAZ activity in Sertoli cell could directly lead to the recruitment of macrophages. Sertoli cells were recently shown to be responsible for the colonization of the gonad by monocytes, which subsequently differentiate into macrophages 85 . Since Cyr61 is expressed in the developing Sertoli cells, 22 it would be interesting to determine if low basal activity of YAP/TAZ in Sertoli cells normally contributes to the recruitment of immune cells to the gonad.…”

Comparative transcriptomic and proteomic signature of lung alveolar macrophages reveals the integrin CD11b as a regulatory hub during pneumococcal pneumonia infection

“…In particular, monocytes that can differentiate into monocyte-derived AM (mo-AM) may play a dominant role ( 23 ). This recruitment of mo-AM alters the population of tissue-resident (TR) AM ( 24 , 25 ) and represents an important mechanism for the phenotypic and functional adaptation of AM during infection. Our study does not distinguish between different subpopulations of AM.…”

Fate‐mapping studies in inbred mice: A model for understanding macrophage development and homeostasis?

“…There have been numerous fate mapping studies of the origins and turnover of tissue-resident macrophages in various organs of the mouse, including studies of pancreas, thymus, testis, tongue and adrenal [27][28][29][30][31] since a previous review [2]. They include an analysis of skeletal muscle [32].…”

“…Diversity in turnover kinetics has also been described for sub-populations of macrophages defined by surface markers within individual tissues (e.g. [27,28,31]).…”