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Key Event Title
Malformation, cryptorchidism - maldescended testis
|Level of Biological Organization|
Key Event Components
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|Cyp17A1 inhibition leads to undescended testes in mammals||AdverseOutcome||Bérénice COLLET (send email)||Open for citation & comment|
|Androgen receptor antagonism and testicular cancer||KeyEvent||Chander K. Negi (send email)||Under development: Not open for comment. Do not cite|
|Adverse Outcome Pathways diagram related to PBDEs associated male reproductive toxicity||AdverseOutcome||Yue Zhang (send email)||Under development: Not open for comment. Do not cite|
Key Event Description
Undescended testis is a testicular disorder syndrome known as cryptorchidism. Testis migration is a major event in male fetus development, as it will directly affect his reproductive health.
Cryptorchidism can defined itself as the insertion of the testis in another position than the scrotum. Although the events leading to this pathology occurred during development, cryptorchidism can only be defined after birth though clinical examination as palpation.
Cryptorchidism can be either uni- or bilateral and has been reported to increase in incidence over the decades (Denmark, UK, India…). The maldescended testis will experiment heat stress (37 against 33C outside the body) interfering with testicular physiology and development of germ cells into spermatogonia. Germ cells maturation failure will induce a non-reversible reduction in fertility power of the individual. Cryptorchidism is an established risk factor for infertility and is known to increase the incidence of testicular germ cell tumors (TGCT) 123
Cryptorchidism is the first AO of a larger list including raise in testicular cancer and germ cell tumor incidence, as well as reduced fertility due to impairment in germ cells maturation.
How It Is Measured or Detected
Cryptorchidism is a birth defect that can be highlighted by a clinical examination. The aim of this palpation is to locate the gonad and determine its lowest position without causing painful traction on the spermatic cord. 4
Domain of Applicability
Regulatory Significance of the Adverse Outcome
1 Hutson J.M., Li R., Southwell B.R., Newgreen D., and Cousinery M. (2015) Regulation of testicular descent. Pediatric Surgery International, 31(4): 317-325. https://doi.org/10.1007/s00383-015-3673-4
2 Boisen K.A., Kaleva M., Main K.M., Virtanen H.E., Haavisto A.M., Schmidt I.M., Chellakooty M., Damgaard I.N., Mau C., Reunanen M., Skakkebaek N.E. and Toppari J. (2004) Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries. Lancet, 17;363(9417):1264-9 https://doi.org/10.1016/S0140-6736(04)15998-9
3 Acerini C.L., Miles H.L., Dunger D.B., Ong K.K. and Hughes I.A. (2009) The descriptive epidemiology of congenital and acquired cryptorchidism in a UK infant cohort. Archives of disease in childhood, 94(11):868-72 https://doi.org10.1136/adc.2008.150219
4 Hutson J.M., et al. (2015) Cryptorchidism and Hypospadias. Endotexthttps://www.ncbi.nlm.nih.gov/books/NBK279106/