Atualmente, sua etiologia é desconhecida. No entanto, vários fatores etiológicos foram sugeridos:
Hormonal: os pacientes podem apresentar anormalidades nas vias/sinalização da testosterona, substância inibidora mülleriana, hormônio 3 semelhante à insulina ou seu receptor LGR8, fator de crescimento epidérmico e/ou estrogênios.[11]Ivell R, Hartung S. The molecular basis of cryptorchidism. Mol Hum Reprod. 2003 Apr;9(4):175-81.
https://academic.oup.com/molehr/article/9/4/175/1080715
http://www.ncbi.nlm.nih.gov/pubmed/12651898?tool=bestpractice.com
[12]Verkauskas G, Malcius D, Eidukaite A, et al. Prospective study of histological and endocrine parameters of gonadal function in boys with cryptorchidism. J Pediatr Urol. 2016 Aug;12(4):238.e1-6.
http://www.ncbi.nlm.nih.gov/pubmed/27321556?tool=bestpractice.com
[13]Hutson JM, Lopez-Marambio FA. The possible role of AMH in shortening the gubernacular cord in testicular descent: a reappraisal of the evidence. J Pediatr Surg. 2017 Oct;52(10):1656-60.
http://www.ncbi.nlm.nih.gov/pubmed/28599968?tool=bestpractice.com
Toxinas ambientais ou maternas: organoclorados, estrogênios ambientais, ésteres de ftalatos e pesticidas foram associados ao aumento do risco de criptorquidia, embora a atual literatura seja inconclusiva.[5]Brucker-Davis F, Pointis G, Chevallier D, et al. Update on cryptorchidism: endocrine, environmental and therapeutic aspects. J Endocrinol Invest. 2003 Jun;26(6):575-87.
http://www.ncbi.nlm.nih.gov/pubmed/12952375?tool=bestpractice.com
[10]Vidaeff AC, Sever LE. In utero exposure to environmental estrogens and male reproductive health: a systematic review of biological and epidemiologic evidence. Reprod Toxicol. 2005 May-Jun;20(1):5-20.
http://www.ncbi.nlm.nih.gov/pubmed/15808781?tool=bestpractice.com
[14]Damgaard IN, Skakkebaek NE, Toppari J, et al. Persistent pesticides in human breast milk and cryptorchidism. Environ Health Perspect. 2006 Jul;114(7):1133-8.
https://ehp.niehs.nih.gov/doi/full/10.1289/ehp.8741
http://www.ncbi.nlm.nih.gov/pubmed/16835070?tool=bestpractice.com
[15]Fratrić I, Varga J, Vukmirović S, et al. Cryptorchidism and pesticides: Is there a connection? J Pediatr Surg. 2017 Jul;52(7):1166-8.
http://www.ncbi.nlm.nih.gov/pubmed/27956069?tool=bestpractice.com
[16]Goodyer CG, Poon S, Aleksa K, et al. A case-control study of maternal polybrominated diphenyl ether (PBDE) exposure and cryptorchidism in Canadian populations. Environ Health Perspect. 2017 May 26;125(5):057004.
https://ehp.niehs.nih.gov/doi/10.1289/EHP522
http://www.ncbi.nlm.nih.gov/pubmed/28557710?tool=bestpractice.com
[17]Sathyanarayana S, Grady R, Barrett ES, et al. First trimester phthalate exposure and male newborn genital anomalies. Environ Res. 2016 Nov;151:777-82.
http://www.ncbi.nlm.nih.gov/pubmed/27567446?tool=bestpractice.com
[18]Le Moal J, Goria S, Guillet A, et al. Time and spatial trends of operated cryptorchidism in France and environmental hypotheses: a nationwide study from 2002 to 2014. Hum Reprod. 2021 Apr 20;36(5):1383-94.
https://www.doi.org/10.1093/humrep/deaa378
http://www.ncbi.nlm.nih.gov/pubmed/33728432?tool=bestpractice.com
[19]Estors Sastre B, Campillo Artero C, González Ruiz Y, et al. Occupational exposure to endocrine-disrupting chemicals and other parental risk factors in hypospadias and cryptorchidism development: a case-control study. J Pediatr Urol. 2019 Oct;15(5):520.e1-520.e8.
http://www.ncbi.nlm.nih.gov/pubmed/31405798?tool=bestpractice.com
O consumo de bebidas alcoólicas, o consumo de analgésicos e o tabagismo maternos têm também sido associados a aumento do risco, embora estes dados sejam conflitantes.[20]Mongraw-Chaffin ML, Cohn BA, Cohen RD, et al. Maternal smoking, alcohol consumption, and caffeine consumption during pregnancy in relation to a son's risk of persistent cryptorchidism: a prospective study in the Child Health and Development Studies cohort, 1959-1967. Am J Epidemiol. 2008 Feb 1;167(3):257-61.
https://academic.oup.com/aje/article/167/3/257/132230
http://www.ncbi.nlm.nih.gov/pubmed/18024986?tool=bestpractice.com
[21]Jensen MS, Rebordosa C, Thulstrup AM, et al. Maternal use of acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy and risk of cryptorchidism. Epidemiology. 2010 Nov;21(6):779-85.
http://www.ncbi.nlm.nih.gov/pubmed/20805751?tool=bestpractice.com
[22]Philippat C, Giorgis-Allemand L, Chevrier C, et al. Analgesics during pregnancy and undescended testis. Epidemiology. 2011 Sep;22(5):747-9.
http://www.ncbi.nlm.nih.gov/pubmed/21811116?tool=bestpractice.com
[23]Hackshaw A, Rodeck C, Boniface S. Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls. Hum Reprod Update. 2011 Sep-Oct;17(5):589-604.
https://academic.oup.com/humupd/article/17/5/589/760093
http://www.ncbi.nlm.nih.gov/pubmed/21747128?tool=bestpractice.com
[24]Damgaard IN, Jensen TK, Petersen JH, et al. Cryptorchidism and maternal alcohol consumption during pregnancy. Environ Health Perspect. 2007 Feb;115(2):272-7.
https://ehp.niehs.nih.gov/doi/full/10.1289/ehp.9608
http://www.ncbi.nlm.nih.gov/pubmed/17384777?tool=bestpractice.com
Demonstrou-se que o diabetes gestacional e/ou a obesidade estão relacionados com o desenvolvimento de criptorquidia.[24]Damgaard IN, Jensen TK, Petersen JH, et al. Cryptorchidism and maternal alcohol consumption during pregnancy. Environ Health Perspect. 2007 Feb;115(2):272-7.
https://ehp.niehs.nih.gov/doi/full/10.1289/ehp.9608
http://www.ncbi.nlm.nih.gov/pubmed/17384777?tool=bestpractice.com
Genético: até 23% dos casos foram associados a agrupamento hereditário, o que sugere uma mutação genética subjacente como etiologia nestes pacientes.[25]Carragher AM, McLean RD. Familial bilateral cryptorchidism. Br J Clin Pract. 1990 Dec;44(12):688-9.
http://www.ncbi.nlm.nih.gov/pubmed/1983232?tool=bestpractice.com
[26]Elert A, Jahn K, Heidenreich A, et al. The familial undescended testis [in German]. Klin Padiatr. 2003 Jan-Feb;215(1):40-5.
http://www.ncbi.nlm.nih.gov/pubmed/12545425?tool=bestpractice.com
Mutações específicas incluem as que envolvem o fator 3 semelhante à insulina e seu receptor, LGR8 e repetições de CAG/GGC nos genes receptores de androgênio.[27]Ferlin A, Bogatcheva NV, Gianesello L, et al. Insulin-like factor 3 gene mutations in testicular dysgenesis syndrome: clinical and functional characterization. Mol Hum Reprod. 2006 Jun;12(6):401-6.
https://academic.oup.com/molehr/article/12/6/401/1044750
http://www.ncbi.nlm.nih.gov/pubmed/16687567?tool=bestpractice.com
[28]Feng S, Cortessis V, Hwang A, et al. Mutation analysis of INSL3 and GREAT/LGR8 genes in familial cryptorchidism. Urology. 2004 Nov;64(5):1032-6.
http://www.ncbi.nlm.nih.gov/pubmed/15533513?tool=bestpractice.com
[29]Wang Y, Wei Y, Tang X, et al. Association between androgen receptor polymorphic CAG and GGC repeat lengths and cryptorchidism: a meta-analysis of case-control studies. J Pediatr Urol. 2018 Jun 7;14(5):432.e1-9.
http://www.ncbi.nlm.nih.gov/pubmed/29914823?tool=bestpractice.com
[30]Wang Q, Ge X, Wang HX, et al. Association of androgen receptor gene CAG and GGN repeat polymorphism with cryptorchidism: a meta-analysis. Andrologia. 2017 Oct 18;50(3):e12909.
http://www.ncbi.nlm.nih.gov/pubmed/29044734?tool=bestpractice.com
Aproximadamente 3% dos meninos com criptorquidia isolada apresentam uma anomalia cromossômica.[31]Ahmed SF, Achermann J, Alderson J, et al. Society for Endocrinology UK Guidance on the initial evaluation of a suspected difference or disorder of sex development (Revised 2021). Clin Endocrinol (Oxf). 2021 Dec;95(6):818-40.
https://onlinelibrary.wiley.com/doi/10.1111/cen.14528
http://www.ncbi.nlm.nih.gov/pubmed/34031907?tool=bestpractice.com
[32]Moreno-Garcia M, Miranda EB. Chromosomal anomalies in cryptorchidism and hypospadias. J Urol. 2002 Nov;168(5):2170-2; discussion 2172.
http://www.ncbi.nlm.nih.gov/pubmed/12394752?tool=bestpractice.com
Mecânico: problemas no desenvolvimento do gubernáculo ou fibras do músculo cremastérico, um conduto peritoniovaginal patente ou pressão intra-abdominal prejudicada têm também servido de hipótese para a criptorquidia.[13]Hutson JM, Lopez-Marambio FA. The possible role of AMH in shortening the gubernacular cord in testicular descent: a reappraisal of the evidence. J Pediatr Surg. 2017 Oct;52(10):1656-60.
http://www.ncbi.nlm.nih.gov/pubmed/28599968?tool=bestpractice.com
[33]Lie G, Hutson JM. The role of cremaster muscle in testicular descent in humans and animal models. Pediatr Surg Int. 2011 Dec;27(12):1255-65.
http://www.ncbi.nlm.nih.gov/pubmed/22038274?tool=bestpractice.com
[34]Arena S, Favaloro A, La Face A, et al. Altered integrins expression of patients affected by cryptorchidism. Urol Int. 2018 Aug 8;101(2):219-23.
http://www.ncbi.nlm.nih.gov/pubmed/30089289?tool=bestpractice.com
[35]Favorito LA, Anderson KM, Costa SF, et al. Structural study of the cremaster muscle in patients with retractile testis. J Pediatr Surg. 2017 Apr 28;53(4):780-3.
http://www.ncbi.nlm.nih.gov/pubmed/28495418?tool=bestpractice.com
Neuromuscular: anormalidades do peptídeo relacionado ao gene da calcitonina do nervo genitofemoral ou do núcleo cremastérico foram postuladas como causadoras de criptorquidia.[36]Hutson JM, Hasthorpe S. Abnormalities of testicular descent. Cell Tissue Res. 2005 Oct;322(1):155-8.
http://www.ncbi.nlm.nih.gov/pubmed/15965656?tool=bestpractice.com