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.

Parent-of-origin effects of A1CF and AGO2 on testicular germ-cell tumors, testicular abnormalities, and fertilization bias

“…By contrast, Ago2 KO/+ heterozygosity increased the occurrence of cryptorchism, but not atrophy, only in intercrosses, whereas TGCT risk was reduced specifically in maternal Ago2 KO/+ backcrosses. Interestingly, as observed in humans (18,(21)(22)(23), a strong association was also found between cryptorchism and TGCTs in 129/Sv controls, with cooccurrence fourfold greater than independent occurrence (Table S2). Reproductive performance.…”

“…Individually and collectively, however, these susceptibility genes account for only a modest portion of inherited risk. Many genes and inherited factors remain to be discovered, their functions in normal development characterized, and the ways that dysfunction leads to TGCTs investigated (16,17).Risk for TGCTs is strongly associated with various testicular abnormalities (TAs) such as undescended testis (cryptorchism) and testicular atrophy (18)(19)(20)(21)(22)(23). This association, sometimes referred to as "testicular dysgenesis syndrome," suggests shared genetic and environmental origins for TGCTs and abnormalities in urogenital development (24)(25)(26).…”

Male Infertility as a Circumstance of Discovery of Adult Cryptorchidism: A Retrospective Analysis from the Region of Thies

“…Thus, this period varies from 15 years according to Swerdlow [18] to 29.4 years according to Toledano [19] between 20 and 49 years. Dysgenesis of the gonad, irreversible even after pulling down the testicle and orchidopexia, are at the origin of the tumors [20]. In all cases, it is recommended to lower the testicle to improve spermato- …”

Is Male Infertility a Natural Defense or Forerunner of Cancer?

“…These genes and its products are synthesis in the epithelial cell of prostate gland and thereafter secreted into the seminal plasma [134]. Study by Wu et.al [135] reported epidemiologic evidence supporting the involvement of common genetic polymorphism in MSMB gene in spermatogenic failure. These results thus suggest that men carry the variant have increased risk of spermatogenic failure associated with male infertility.…”