Cryptorchidism: The dog as a study model

Hernández-Jardón, Norma; Rojas-Castañeda, Julio César; Landero-Huerta, Daniel Adrian; Reyes-Cruz, Estefanía; Reynoso-Robles, Rafael; Juárez-Mosqueda, María del Lourdes; Medrano, Alfredo Soriano; Reyes-Delgado, Fausto; Vigueras-Villaseñor, Rosa María

doi:10.3389/fvets.2022.935307

Cited by 4 publications

(1 citation statement)

References 85 publications

(97 reference statements)

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“…These latter are more similar to humans in terms of size, life span, physiology and genetics than laboratory animals, and hence are used as models in biomedical research (Harkey et al, 2013). Different studies suggest this species as a suitable experimental model of testicular diseases in humans (Hernández‐Jardón et al, 2022; Jhun et al, 2022; Saleh et al, 1989; Turner, 2001). From the veterinary aspect, several disorders like orchitis, cryptorchidism, neoplasia and cysts have been reported to affect the testis in dogs (Foster, 2012).…”

Section: Introductionmentioning

confidence: 99%

Three‐dimensional morphometry of the testis in dog using design‐unbiased stereology

Bojarzadeh,

Lazzarini,

Gatta

et al. 2023

Anat Histol Embryol

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Testis is considered the main organ of the male reproductive system. Dogs are used as a suitable experimental model of testicular diseases in humans. From the veterinary aspect, several disorders have been reported to affect the testis in dogs. Thus, the objective of the present study was to investigate the morphometrical features of the dog testis using design‐based stereology. The testes of six male dogs were used. Isotropic, uniform random sections were obtained and processed for light microscopy. Testicular total volume and the fractional volume of the seminiferous tubules, interstitial tissue and germinal epithelium were measured using the Cavalieri's estimator and the point counting system. Germinal epithelial surface area was estimated using test lines, and total length of seminiferous tubules was analysed using the counting frames. The total volume of testis was calculated 13.64 ± 1.94 cm3. The relative volume fractions of the seminiferous tubules, interstitial tissue and germinal layer expressed as a percentage of total testicular volume were found to be 75.87 ± 6.11%, 23.68 ± 5.15% and 64.15 ± 4.82%, respectively. The surface area of the germinal layer was 915.25 ± 150.48 cm2. The thickness of germinal layer was estimated to be 96.18 ± 10.72 μm. The total length of seminiferous tubules measured 290.8 ± 35.86 m. No statistical difference in investigated parameters was found between the left and right testes (p > 0.05). Our data might contribute to the male reproductive knowledge, help develop experimental studies in this field and possibly lead to advancement in the diagnosis and treatment of testicular diseases in the dog.

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Section: Introductionmentioning

confidence: 99%

Three‐dimensional morphometry of the testis in dog using design‐unbiased stereology

Bojarzadeh,

Lazzarini,

Gatta

et al. 2023

Anat Histol Embryol

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A massive alteration of gene expression in undescended testicles of dogs and the association of KAT6A variants with cryptorchidism

Stachowiak,

Nowacka-Woszuk,

Szabelska-Beresewicz

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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Cryptorchidism is the most common form of disorder of sex development in male dogs, but its hereditary predisposition is poorly elucidated. The gonadal transcriptome of nine unilaterally cryptorchid dogs and seven control dogs was analyzed using RNA-seq. Comparison between the scrotal and inguinal gonads of unilateral cryptorchid dogs revealed 8,028 differentially expressed genes (DEGs) (3,377 up-regulated and 4,651 down-regulated). A similar number of DEGs (7,619) was found by comparing the undescended testicles with the descended testicles of the control dogs. The methylation status of the selected DEGs was also analyzed, with three out of nine studied DEGs showing altered patterns. Bioinformatic analysis of the cDNA sequences revealed 20,366 SNP variants, six of which showed significant differences in allelic counts between cryptorchid and control dogs. 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.

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Cryptorchidism and testicular cancer in the dog: unresolved questions and challenges in translating insights from human studies

Soto-Heras,

Reinacher,

Wang

et al. 2024

Biology of Reproduction

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Cryptorchidism, the failure of one or both testes to descend into the scrotum, and testicular cancer show a strong correlation in both dogs and humans. Yet, long-standing medical debates persist about whether the location of undescended testes directly causes testicular cancer in humans or if both conditions stem from a common origin. Although testicular cancer is a prevalent disease in dogs, even less is known about its cause and correlation with testicular descent in this species. This review investigates the relation between these two disorders in dogs, drawing insights from human studies, and examines key biomarkers identified thus far. In addition, it explores potential causal links, including the impact of temperature on maturing testicular cells and a potential shared genetic origin. Notably, this literature review reveals significant differences between men and dogs in reproductive development, histological and molecular features of testicular tumors, and the prevalence of specific tumor types, such as Sertoli cell tumors (SCTs) in cryptorchid dogs and germ cell tumors (GCTs) in humans. These disparities caution against using dogs as models for human testicular cancer research and underscore the limitations when drawing comparisons between species. The paper concludes by suggesting specific research initiatives to enhance our understanding of the complex interplay between cryptorchidism and testicular cancer in dogs.

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Cryptorchidism: The dog as a study model

Cited by 4 publications

References 85 publications

Three‐dimensional morphometry of the testis in dog using design‐unbiased stereology

Three‐dimensional morphometry of the testis in dog using design‐unbiased stereology

A massive alteration of gene expression in undescended testicles of dogs and the association of KAT6A variants with cryptorchidism

Cryptorchidism and testicular cancer in the dog: unresolved questions and challenges in translating insights from human studies

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