Testicular cancer and cryptorchidism

Abstract

The failure of testicular descent or cryptorchidism is the most common defect in newborn boys. The descent of the testes during development is controlled by insulin-like 3 peptide and steroid hormones produced in testicular Leydig cells, as well as by various genetic and developmental factors. While in some cases the association with genetic abnormalities and environmental causes has been shown, the etiology of cryptorchidism remains uncertain. Cryptorchidism is an established risk factor for infertility and testicular germ cell tumors (TGCT). Experimental animal models suggest a causative role for an abnormal testicular position on the disruption of spermatogenesis however the link between cryptorchidism and TGCT is less clear. The most common type of TGCT in cryptorchid testes is seminoma, believed to be derived from pluripotent prenatal germ cells. Recent studies have shown that seminoma cells and their precursor carcinoma in situ cells express a number of spermatogonial stem cell (SSC) markers suggesting that TGCTs might originate from adult stem cells. We review here the data on changes in the SSC somatic cell niche observed in cryptorchid testes of mouse models and in human patients. We propose that the misregulation of growth factors' expression may alter the balance between SSC self-renewal and differentiation and shift stem cells toward neoplastic transformation.

Keywords: cryptorchidism; somatic cell niche; spermatogonial stem cells; testicular cancer; testis.

Figure 1

Schematic representation of the origin of testicular germ cell tumors (TGCTs) in humans. Normal spermatogonial stem cells (SSCs) A_dark and A_pale either undergo a cycle of self-renewal or begin to differentiate and are controlled by the expression of somatic growth factors. Classical seminomas are derived from carcinoma in situ cells (CIS). Spermatocytic seminomas originate from differentiating spermatogonia.