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

Background/Aim: Cryptorchidism, or undescended testis (UDT) occurs in 15-45 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 assessthe 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 developmentare now characterized, but the factors involved in gonocyte transformation and apoptosis in both normal and cryptorchicl 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 cryptorch id 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 riUDT may be caused by abnormalities in germ cell development dung minipuberty. Type of study: Systematic review (secondary, filtered) (C) 2019 Elsevier Inc. All rightsreserved.