EGR4 is a master gene responsible for fertility in cryptorchidism.

The purpose of early medical or surgical treatment of boys with undescended testes is to prevent the development of infertility. However, early and successful surgery cannot prevent infertility in cryptorchid boys who lack type A dark (Ad) spermatogonia. The aim of this study was to compare the gene expression pattern of patients with completed transformation of gonocytes into Ad spermatogonia, associated with low infertility risk, with patients that had failed to undergo this process and had a high infertility risk. Genes expressed in the 16 cryptorchid testes were estimated using Affymetrix whole-genome microarray and compared to the expression profiles from four contralateral gonads of boys with unilateral testicular agenesis. Whole-genome expression profiling showed that boys in the high infertility risk group according to testicular histology, showed decreased or lack of expression of most of the genes essential for hypothalamo-pituitary-testicular axis function relative to low or intermediate risk group as well as controls. In particular, EGR4, which is involved in regulating the secretion of luteinizing hormone, was virtually not expressed. Thus, we found multiple differences in gene expression between the high and low infertility risk groups, confirming the importance of an intact hypothalamo-pituitary testicular axis and EGR4 in fertility development.