Trem2-dependent Insl3 regulation via Dap12-Syk-PI3K pathway: A new pathogenic mechanism in cryptorchidism.

Genomics 2025

Ye S, Wu C, Huang S, Fan H, Zhang Z et al.

Abstract

Cryptorchidism, affecting 1 %-9 % of male neonates, represents one of the most prevalent congenital genitourinary anomalies. Studies highlighted Leydig cell derived insulin-like 3 (Insl3) as pivotal in the initial phase of testicular descent. However, the pathogenic mechanisms underlying decreased Insl3 remain poorly elucidated. Here, we showed that triggering receptor expressed on myeloid cells-2 (Trem2) acted as a central mediator in macrophage-Leydig cell communication, influencing testicular descent via Insl3 regulation. In boys with cryptorchidism, Trem2 in testes was markedly downregulated. 63.16 % of Trem2

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