PDGF-AA activates AKT and ERK signaling for testicular interstitial Leydig cell growth via primary cilia

Testes control the development of male reproductive system. The testicular interstitial Leydig cells (Leydig cells) synthesize testosterone for promoting spermatogenesis and secondary sexual characteristics. Type A platelet-derived growth factor (PDGF-AA) is one of the most important growth factors in regulating Leydig cell growth and function. Knockout of PDGF-AA or its congenital receptor PDGFR-alpha leads to poor testicular development caused by reducing Leydig cell numbers, supporting PDGF-AA/PDGFR-alpha signaling regulates Leydig cell development. Primary cilium is a cellular antenna that functions as an integrative platform to transduce extracellular signaling for proper development and differentiation. Several receptors including PDGFR-alpha are observed on primary cilia for initiating signaling cascades in distinct cell types. Here we showed that PDGF-AA/PDGFR-alpha signaling promoted Leydig cells growth, migration, and invasion via primary cilia. Upon PDGF-AA treatment, AKT and ERK signaling were activated to regulate these cellular events. Interestingly, active AKT and ERK were detected around the base of primary cilia. Depletion of ciliary genes (IFT88 and CEP164) alleviated PDGF-AA-activated AKT and ERK, thus reducing Leydig cell growth, migration, and invasion. Thus, our study not only reveals the function of PDGF-AA/PDGFR-alpha signaling in maintaining testicular physiology but also uncovers the role of primary cilium and downstream signaling in regulating Leydig cell development.

Automated summary

Testes play a crucial role in the development of the male reproductive system. This study demonstrates that the PDGF-AA/PDGFR-alpha signaling pathway regulates Leydig cell development and function through primary cilia. The activation of AKT and ERK signaling around the base of primary cilia promotes Leydig cell growth, migration, and invasion. Understanding the role of primary cilia and downstream signaling in testicular physiology provides important insights into male reproductive health.