Cryptorchidism, gonocyte development, and the risks of germ cell malignancy and infertility: A systematic review.

BACKGROUND/AIM: Cryptorchidism, or undescended testis (UDT) occurs in 1%-4% of newborn males and leads to a risk of infertility and testicular malignancy. Recent research suggests that infertility and malignancy in UDT may be caused by abnormal development of the neonatal germ cells, or gonocytes, which normally transform into spermatogonial stem cells (SSC) or undergo apoptosis during minipuberty at 2-6 months in humans (2-6 days in mice). We aimed to identify the current knowledge on how UDT is linked to infertility and malignancy.

METHODS

Here we review the literature from 1995 to the present to assess the possible causes of infertility and malignancy in UDT, from both human studies and animal models.

RESULTS

Both the morphological steps and many of the genes involved in germ cell development are now characterized, but the factors involved in gonocyte transformation and apoptosis in both normal and cryptorchid testes are not fully identified. During minipuberty there is evidence for the hypothalamic-pituitary axis stimulating gonocyte transformation, but without known direct control by LH and androgen, although FSH may have a role. An arrested gonocyte maybe the origin of later malignancy at least in syndromic cryptorchid testes in humans, which is consistent with the recent finding that gonocytes are normally absent in a rodent model of congenital cryptorchidism, where malignancy has not been reported.

CONCLUSION

The results of this review strengthen the view that malignancy and infertility in men with previous UDT may be caused by abnormalities in germ cell development during minipuberty.

TYPE OF STUDY: Systematic review (secondary, filtered) LEVEL OF EVIDENCE: Level I.