1.Sertoli cell transcriptome sequencing; 2.Palmitic acid induces inflammatory responses and endoplasmic reticulum stress in sertoli cells; 3.High fat diet induces male infertility in the process of sperm production.
A high fat diet is a dietary pattern characterized by an increased proportion of saturated fatty acids. This diet can induce inflammatory responses in testicular sertoli cells, leading to their apoptosis and ultimately causing spermatogenic dysfunction. high fat diet is closely related to the activation of the IRE1A/TRAF2/NFKB mediated inflammatory response. However, whether the IRE1A/TRAF2/NFKB signaling pathway mediated inflammatory response is associated with high fat diet induced Sertoli cell apoptosis remains unclear. In this study, we found thathigh fat diet could cause inflammatory responses in mouse testicular Sertoli cells, resulting in a reduction in the number of Sertoli cells and subsequent spermatogenic dysfunction. Additionally, we discovered that palmitic acid (PA), a major component of high fat diet, could induce inflammatory responses and apoptosis in TM4 cells in a concentration dependent manner, and PA could upregulate the IRE1A/TRAF2/NFKB signaling pathway in sertoli cells. TRAF2 gene silencing and inhibition of IRE1A kinase activity further confirmed that PA could induce inflammatory responses in TM4 cells by upregulating the IRE1A/TRAF2/NFKB signaling pathway, thereby causing apoptosis. In summary, HFD can induce inflammatory responses in Sertoli cells by upregulating the IRE1A/TRAF2/NFKB signaling pathway, leading to Sertoli cell apoptosis. This finding provides a potential target for the prevention and treatment of high fat diet induced spermatogenic dysfunction in men