Decoding mechanisms and therapeutic opportunities in testicular development diseases through macrophage immunology.

Testicular development is a complex biological process that relies on three critical elements: proper anatomical development of the reproductive system, precise hormonal regulation, and coordinated interactions among various cell populations sustaining a functional micro-environment within the testis. The testicular immune micro-environment is essential for normal testicular development. As principal regulatory components of this specialized niche, testicular macrophages demonstrate remarkable functional and phenotypic diversity, serving as critical mediators of immune homeostasis within the testis. Immune signaling molecules associated with macrophages shape the immune landscape of testicular diseases through signal transduction and transcriptional and post-transcriptional mechanisms. Based on a specific account of the function of testicular macrophages on the testis and signaling molecular exchanges between the various cells, this review reveals the pathogenic mechanisms of testicular macrophages in a range of testicular developmental diseases. It provides suggestions for the design of new immunotherapies.