OMIA:000243-9615 : Cryptorchidism in Canis lupus familiaris (dog)

In other species: domestic cat , puma , horse , pig , Arabian camel , llama , taurine cattle , goat , sheep , domestic yak , alpaca

Categories: Reproductive system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 219050 (trait)

Links to relevant human diseases in MONDO:

Mendelian trait/disorder: no

Mode of inheritance: Multifactorial

Considered a defect: yes

Key variant known: no

Cross-species summary: Failure of one (unilateral) or both (bilateral) testes to descend.

Species-specific description: Cryptorchidism is characterized by the presence of one or two undescended testes in an otherwise phenotypically normal male (isolated cryptorchidism). Canine cryptorchidism is common in the dog population as a whole, with high prevalence in some breeds. Undescended testes have an increased risk of developing neoplasia. Breeding of affected dogs is discouraged. Edited by Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACT, modified by Imke Tammen [28/09/2023]

Inheritance: Inheritance of this condition is recessive and polygenic, with contributions from epigenetic and environmental factors (Zhao et al., 2010).

Mapping: By conducting a GWAS on 106 affected and 99 normal male Siberian Huskies, each genotyped with the 170K CanineHD BeadChip (yielding 120,379 informative SNPs), Zhao et al. (2014) identified "six putative genomic candidate regions on CFA6, 9, 24, 27 and X". Blades et al. (2022) identified a variant in HMGA2 that was associated with inguinal cryptorchidism in an across-breed GWAS, but within-breed GWAS failed to replicate this association in any breed, and failed to identify any other potential marker.

 

Markers: Krzeminska et al. (2020) concluded that a "SNP in CYP17A1 and an indel in CYP19A1 . . . cannot be considered markers associated with a predisposition to cryptorchidism".

Stachowiak et al. (2024) "The gonadal transcriptome of nine unilaterally cryptorchid dogs and seven control dogs was analyzed using RNA-seq. ... Validation studies in larger cohorts of cryptorchid (n = 122) and control (n = 173) dogs showed that the TT genotype (rs850666472, p.Ala1230Val) and the AA genotype in 3'UTR (16:23716202G>A) in KATA6, responsible for acetylation of lysine 9 in histone H3, are associated with cryptorchidism (P = 0.0383). Both the transcript level of KAT6A and H3K9 acetylation were lower in undescended testes, and additionally, the acetylation depended on the genotypes in exon 17 and the 3'UTR. Our study showed that the massive alteration of the transcriptome in undescended testicles is not caused by germinal DNA variants in DEG regulatory sequences but is partly associated with an aberrant DNA methylation and H3K9 acetylation patterns. Moreover, variants of KAT6A can be considered markers associated with the risk of this disorder."

Clinical features: Undescended testes may be located anywhere from the caudal pole of the kidney to the inguinal canal, or outside of the canal but cranial to the scrotum (Meyers-Wallen, 2011). Canine testes normally pass through the inguinal canal within 10 days after birth (Gier and Marion, 1969), but scrotal testes are not easily palpable in neonates. Dogs can be considered cryptorchid if one or both testes are not palpable in the scrotum by 6 to 8 weeks of age (Meyers-Wallen, 2011). Later testis descent can occur, and is more common with unilaterally cryptorchid dogs (Dunn et al., 1968).

Pathology: There is an increased risk of neoplasia (Sertoli cell tumor, seminoma) in undescended testes. Unilateral cryptorchid dogs may have reduced fertility and bilateral cryptorchid dogs are sterile, as spermatogonia are depleted in undescended testes. Cryptorchid testes can occur in association with other DSD, such as Persistent Mullerian duct syndrome, AMHR2-related in Miniature Schnauzers (OMIA:002775-9615) and XX difference of sexual development (OMIA:000901-9615) in several breeds. As testes descend, they transit through the abdomen and inguinal canal to the scrotum. Testosterone and INSL3 (insulin like factor 3), both secreted by Leydig cells, induce the growth and differentiation in the gubernaculum, which is needed for normal testicular descent. Mutations in INSL3 or its receptor (LGR8/GREAT) cause cryptorchidism in humans, but no analogous mutations have been discovered in dogs. Human males with heterozygous INSL3 mutations are unilaterally cryptorchid at birth, but the testis descends later, usually at puberty (Tomboc et al., 2000, Ferlin et al., 2003). Other candidate genes for cryptorchidism in humans are the androgen receptor (AR) and estrogen receptor (ER, Pathirana, 2010).

Prevalence: Canine isolated cryptorchidism is common, with different studies reporting prevalence from 6.8% of males presented for neutering to 1.4% of dogs at 6-12 months of age (Hayes et al., 1985, Yates et al., 2003). Prevalence is higher in Siberian Husky dogs, and in smaller breeds compared to larger breeds (Zhao et al., 2010, Pathirana et al., 2010).

Control: Breeding of fertile cryptorchid animals (as well as their parents or siblings) is discouraged. The AVMA states that it is unethical for a veterinarian to surgically correct cryptorchidism without also sterilizing the animal.

Genetic testing: There are no reliable genetic tests available at this time.

Breed: Siberian Husky (Dog) (VBO_0201233).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:000243-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

References

Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2024 Liguori, G., Tafuri, S., Pelagalli, A., Ali', S., Russo, M., Mirabella, N., Squillacioti, C. :
G protein-coupled estrogen receptor (GPER) and ERs are modulated in the testis-epididymal complex in the normal and cryptorchid dog. Vet Sci 11:21, 2024. Pubmed reference: 38250927. DOI: 10.3390/vetsci11010021.
Soto-Heras, S., Reinacher, L., Wang, B., Oh, J.E., Bunnell, M., Park, C.J., Hess, R.A., Ko, C.J. :
Cryptorchidism and testicular cancer in the dog: unresolved questions and challenges in translating insights from human studies. Biol Reprod :ioae075, 2024. Pubmed reference: 38738783. DOI: 10.1093/biolre/ioae075.
Stachowiak, M., Nowacka-Woszuk, J., Szabelska-Beresewicz, A., Zyprych-Walczak, J., Krzeminska, P., Sosinski, O., Nowak, T., Switonski, M. :
A massive alteration of gene expression in undescended testicles of dogs and the association of KAT6A variants with cryptorchidism. Proc Natl Acad Sci U S A 121:e2312724121, 2024. Pubmed reference: 38315849. DOI: 10.1073/pnas.2312724121.
2023 Pizzi, G., Groppetti, D., Brambilla, E., Pecile, A., Grieco, V., Lecchi, C. :
MicroRNA as epigenetic regulators of canine cryptorchidism. Res Vet Sci 162:104961, 2023. Pubmed reference: 37487386. DOI: 10.1016/j.rvsc.2023.104961.
2022 Blades, M., Freyer, J., Donner, J., Chodroff Foran, R., Forman, O.P. :
Large scale across-breed genome-wide association study reveals a variant in HMGA2 associated with inguinal cryptorchidism risk in dogs. PLoS One 17:e0267604, 2022. Pubmed reference: 35617214. DOI: 10.1371/journal.pone.0267604.
Krzeminska, P., Nowak, T., Switonski, M. :
Isolated cryptorchidism in dogs is not associated with polymorphisms of the INSL3 and AR candidate genes. Anim Genet 53:233-235, 2022. Pubmed reference: 35080026. DOI: 10.1111/age.13175.
2021 Chai, S., Huang, X., Wu, T., Xu, S., Ren, W., Yang, G. :
Comparative genomics reveals molecular mechanisms underlying health and reproduction in cryptorchid mammals. BMC Genomics 22:763, 2021. Pubmed reference: 34702182. DOI: 10.1186/s12864-021-08084-1.
Pecile, A., Groppetti, D., Pizzi, G., Banco, B., Bronzo, V., Giudice, C., Grieco, V. :
Immunohistochemical insights into a hidden pathology: Canine cryptorchidism. Theriogenology 176:43-53, 2021. Pubmed reference: 34571397. DOI: 10.1016/j.theriogenology.2021.09.011.
2020 Krzeminska, P., Stachowiak, M., Skrzypski, M., Nowak, T., Maslak, A., Switonski, M. :
Altered expression of CYP17A1 and CYP19A1 in undescended testes of dogs with unilateral cryptorchidism. Anim Genet 51:763-771, 2020. Pubmed reference: 32657440. DOI: 10.1111/age.12977.
Nowacka-Woszuk, J., Krzeminska, P., Nowak, T., Gogulski, M., Switonski, M., Stachowiak, M. :
Analysis of transcript and methylation levels of INSL3 and RXFP2 in undescended and descended dog testes suggested promising biomarkers associated with cryptorchidism. Theriogenology 157:483-489, 2020. Pubmed reference: 32898823. DOI: 10.1016/j.theriogenology.2020.08.029.
2019 Krzemińska, P., D'Anza, E., Ciotola, F., Paciello, O., Restucci, B., Peretti, V., Albarella, S., Switonski, M. :
Polymorphisms of MAMLD1, SRD5A2, and AR candidate genes in seven dogs (78,XY; SRY-Positive) affected by hypospadias or cryptorchidism. Sex Dev 13:92-98, 2019. Pubmed reference: 31055572. DOI: 10.1159/000500219.
2018 Khan, F.A., Gartley, C.J., Khanam, A. :
Canine cryptorchidism: An update. Reprod Domest Anim 53:1263-1270, 2018. Pubmed reference: 29956390. DOI: 10.1111/rda.13231.
2014 Zhao, X., Onteru, S., Saatchi, M., Garrick, D., Rothschild, M. :
A genome-wide association study for canine cryptorchidism in Siberian Huskies. J Anim Breed Genet 131:202-9, 2014. Pubmed reference: 24268032. DOI: 10.1111/jbg.12064.
2012 Meyers-Wallen, V.N. :
Gonadal and sex differentiation abnormalities of dogs and cats. Sex Dev 6:46-60, 2012. Pubmed reference: 22005097. DOI: 10.1159/000332740.
Pathirana, I.N., Yamasaki, H., Kawate, N., Tsuji, M., Büllesbach, E.E., Takahashi, M., Hatoya, S., Inaba, T., Tamada, H. :
Plasma insulin-like peptide 3 and testosterone concentrations in male dogs: changes with age and effects of cryptorchidism. Theriogenology 77:550-7, 2012. Pubmed reference: 22015156. DOI: 10.1016/j.theriogenology.2011.08.030.
Quartuccio, M., Marino, G., Garufi, G., Cristarella, S., Zanghì, A. :
Sertoli cell tumors associated with feminizing syndrome and spermatic cord torsion in two cryptorchid dogs. J Vet Sci 13:207-9, 2012. Pubmed reference: 22705745.
2011 Breshears, M.A., Peters, J.L. :
Ambiguous genitalia in a fertile, unilaterally cryptorchid male miniature schnauzer dog. Vet Pathol 48:1038-40, 2011. Pubmed reference: 21248100. DOI: 10.1177/0300985810396104.
2010 Arrighi, S., Bosi, G., Groppetti, D., Aralla, M., Cremonesi, F. :
An insight into testis and gubernaculum dynamics of INSL3-RXFP2 signalling during testicular descent in the dog. Reprod Fertil Dev 22:751-60, 2010. Pubmed reference: 20450827. DOI: 10.1071/RD09260.
Pathirana, IN., Tanaka, K., Kawate, N., Tsuji, M., Kida, K., Hatoya, S., Inaba, T., Tamada, H. :
Analysis of single nucleotide polymorphisms in the 3' region of the estrogen receptor 1 gene in normal and cryptorchid Miniature Dachshunds and Chihuahuas. J Reprod Dev 56:405-10, 2010. Pubmed reference: 20453437.
Zhao, X., Du, ZQ., Rothschild, MF. :
An association study of 20 candidate genes with cryptorchidism in Siberian Husky dogs. J Anim Breed Genet 127:327-31, 2010. Pubmed reference: 20646120. DOI: 10.1111/j.1439-0388.2010.00859.x.
2008 Birchard, SJ., Nappier, M. :
Cryptorchidism. Compend Contin Educ Vet 30:325-36; quiz 336-7, 2008. Pubmed reference: 18690608.
2004 van Hagen, MA., Janss, LL., van den Broek, J., Knol, BW. :
The use of a genetic-counselling program by Dutch breeders for four hereditary health problems in boxer dogs. Prev Vet Med 63:39-50, 2004. Pubmed reference: 15099715. DOI: 10.1016/j.prevetmed.2004.01.007.
2003 Ferlin, A., Simonato, M., Bartoloni, L., Rizzo, G., Bettella, A., Dottorini, T., Dallapiccola, B., Foresta, C. :
The INSL3-LGR8/GREAT ligand-receptor pair in human cryptorchidism. J Clin Endocrinol Metab 88:4273-9, 2003. Pubmed reference: 12970298.
Yates, D., Hayes, G., Heffernan, M., Beynon, R. :
Incidence of cryptorchidism in dogs and cats Veterinary Record 152:502-4, 2003. Pubmed reference: 12733559.
2001 Reif, U., Walshaw, R., Perry, R. :
Urethradiverticulum, persistant urachusligament and torsion of a testis in a kryptorchid dog Kleintierpraxis 46:733-739, 2001.
2000 Tomboc, M., Lee, P.A., Mitwally, M.F., Schneck, F.X., Bellinger, M., Witchel, S.F. :
Insulin-like 3/relaxin-like factor gene mutations are associated with cryptorchidism. J Clin Endocrinol Metab 85:4013-8, 2000. Pubmed reference: 11095425.
1996 Schulz, K.S., Waldron, D.R., Smith, M.M., Henderson, R.A., Howe, L.M. :
Inadvertent prostatectomy as a complication of cryptorchidectomy in four dogs Journal of the American Animal Hospital Association 32:211-214, 1996. Pubmed reference: 8731134.
1995 Kawakami, E., Tsutsui, T., Saito, S., Kakimoto, T., Ogasa, A. :
Changes in peripheral plasma luteinizing hormone and testosterone concentrations and semen quality in normal and cryptorchid dogs during sexual maturation Laboratory Animal Science 45:258-263, 1995. Pubmed reference: 7650895.
1994 Ayyappan, S., Jayaprakash, R., Tank, P.H., David, W.P.A., Balasubramanian, N.N. :
Bilateral Inguinal Cryptorchidism with Sertoli Cell Tumour in a Dog - A Case Report Indian Veterinary Journal 71:915-917, 1994.
1993 Kawakami, E., Hirayama, S., Tsutsui, T., Ogasa, A. :
Pituitary Response of Cryptorchid Dogs to LH-RH-Analogue Before and After Sexual Maturation Journal of Veterinary Medical Science 55:147-148, 1993. Pubmed reference: 8096403.
Metzger, F.L., Hattel, A.L., White, D.G. :
Hematuria, Hyperestrogenemia, and Hyperprogesteronemia Due to a Sertoli-Cell Tumor in a Bilaterally Cryptorchid Dog Canine Practice 18:32-35, 1993.
Ruble, R.P., Hird, D.W. :
Congenital Abnormalities in Immature Dogs from a Pet Store - 253 Cases (1987-1988) Journal of the American Veterinary Medical Association 202:633-636, 1993. Pubmed reference: 8095494.
1991 Romagnoli, S.E. :
Canine cryptorchidism. Vet Clin North Am Small Anim Pract 21:533-44, 1991. Pubmed reference: 1677504. DOI: 10.1016/s0195-5616(91)50059-0.
1989 Vanleeuwen, M.P.M., Hunen, E.J.M.R., Bouw, J. :
Cryptorchidism in Dogs Tijdschrift Voor Diergeneeskunde 114:999-1005, 1989. Pubmed reference: 2572074.
1985 Hayes, H.M., Wilson, G.P., Pendergrass, T.W., Cox, V.S. :
Canine cryptorchism and subsequent testicular neoplasia: case-control study with epidemiologic update. Teratology 32:51-6, 1985. Pubmed reference: 2863879. DOI: 10.1002/tera.1420320108.
1981 Baumans, B., Dijkstra, G., Wensing, C.J.G. :
Testicular descent in the dog. Anat. Histol. Embryol. 10:97-110, 1981. DOI: 10.1111/j.1439-0264.1981.tb00508.x.
1978 Cox, V.S., Wallace, L.J., Jessen, C.R. :
An anatomic and genetic study of canine cryptorchidism. Teratology 18:233-40, 1978. Pubmed reference: 31014. DOI: 10.1002/tera.1420180208.
1970 Turner, T. :
Torsion of the retained testicle in the dog Journal of Small Animal Practice 11:436-437, 1970. Pubmed reference: 4393846.
1969 Gier, H.T., Marion, G.B. :
Development of mammalian testes and genital ducts. Biol Reprod 1:Suppl 1:1-23, 1969. Pubmed reference: 5406326.
Lindo, D,E, Grenn, H.H. :
Bilateral sertoli cell tumor in a canine cryptorchid with accompanying pathological lesions Canadian Veterinary Journal 10:145-147, 1969.
Reif, J.S., Brodey, R.S. :
The relationship between cryptorchidism and canine testicular neoplasia Journal of the American Veterinary Medical Association 155:2005-2010, 1969. Pubmed reference: 4391618.
1960 Willis, M.B. :
Inheritance of cryptorchidism Journal of Animal Health Trust :21-25, 1960.
1955 Anon. :
Cryptorchidism in the dog Veterinary Record 67:472-474, 1955.
1953 Pullig, T. :
Cryptorchidism in Cocker Spaniels. Journal of Heredity 44:250-264, 1953.
1938 Hartl, J. :
Die verebung des Kryptorchismus beim Hund Kleinter u Pesztier 14:1-37, 1938.

Edit History


  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Martha MaloneyHuss on 08 Sep 2011
  • Changed by Frank Nicholas on 27 Nov 2013
  • Changed by Frank Nicholas on 16 Jul 2020
  • Changed by Frank Nicholas on 01 Jun 2022
  • Changed by Frank Nicholas on 10 Apr 2023
  • Changed by Imke Tammen2 on 28 Sep 2023
  • Changed by Imke Tammen2 on 08 Feb 2024