Disordered APC/C-mediated cell cycle progression and IGF1/PI3K/AKT signalling are the potential basis of Sertoli cell-only syndrome.

Abstract

The cause of Sertoli cell-only syndrome (SCOS), a condition in which only Sertoli cells line the seminiferous tubules in the testis, is unknown. Three microarray data sets were downloaded from public databases and were used to compare SCOS and control group. A total of 291 genes differentially expressed (Log2 |FC|≥1 and adjusted p value<0.05) in SCOS patients. Further 238 genes were significantly downregulated, and 53 genes were significantly upregulated. To identify the hub genes in the differentially expressed genes, we constructed a protein-protein interaction network, and CCNB1, CCNA2, AURKA, KIF11, CCNB2, CDC6, PRC1, NCAPG, KIF2C and PLK4 were screened from the network for the downregulated genes. Since the upregulated genes could not form a network, we concentrated on the genes with a higher fold change, and CPA3, NFIB, LONRF2, LYVE1, ATP8B4, IGF1, ITPR1 and PLAT were identified as the top 50% fold change genes in any of the three microarray data sets. Among downregulated hub genes, CDC6, CCNA2, CCNB1 and CCNB2 were involved in APC/C-mediated cell cycle progression. Among key upregulated genes, IGF1 was involved in the PI3K/AKT pathway, while the other genes have not been reported in Sertoli or Leydig cells. In conclusion, SCOS appears to be caused by disordered APC/C-mediated cell cycle progression and PI3K/AKT signalling.