Testicular Maldescent Research Articles

Pre-referral ultrasound for cryptorchidism: Still common, still not necessary.

Evidence-based guidelines do not recommend imaging in cryptorchidism, but anecdotally most referrals include an ultrasound report. We aimed to assess the frequency, utility and burden of imaging in children referred with presumptive disorders of testicular descent, and to assess trends over a 7-year period before and after local and international guidelines have been introduced. This was a prospective cohort study of children referred to the Queensland Children'sHospital for anomalies of testicular descent between 2015-2017 and 2023-2024. Data were collected regarding demographics, referral details, imaging performed and surgical diagnosis. A total of 268 children were recruited. Ultrasound frequency has not significantly changed over time (72.8%, 2015-2017; 63.6% 2023-2024; P = 0.11). Currently, 17.6% of families are charged, and 31.9% need to take time off work, for the ultrasound. This is a significant increase from the 2015-2017 cohort. Parents report concern and anxiety, and find it traumatic for their child. Following review, the majority (65.7%) had physiologically normal testes, while 4.9% and 22.4% were diagnosed with bilateral or unilateral cryptorchidism, respectively, and 7.0% had other diagnoses. Ultrasound was concordant with the surgical diagnosis in 25.0% (2015-2017) and 30.7% (2023-2024). Ultrasound did not contribute to diagnosis nor management in any patient. Despite international and local guidelines, cryptorchid children continue to undergo ultrasound prior to referral. Such ultrasounds do not provide utility, or value for cost. We recommend avoiding their routine use for suspicion of testicular maldescent and working together to improve strategies for translating evidence-based guidelines into clinical practice.

O-248 Cluster Analysis of men with idiopathic and unexplained male infertility identifies FSHB Genotype as relevant diagnostic parameter

Abstract Study question In a cohort of idiopathic and unexplained infertile men we aimed to identify subgroups with similar characteristics, and therewith underlying etiologic factors, by clustering approach. Summary answer We identified two distinct patient clusters. Across all diverse phenotypes of infertility, the strongest segregation markers were FSHB c.-211G>T, FSH, and bi-testicular volume. What is known already In about 30-75% of infertile men no major causative factors can be identified; leading to the diagnose of unexplained (normozoospermia) or idiopathic (abnormal semen parameters) male infertility. This cohort of men remains very heterogenous, albeit the detailed andrological characterization that is currently applied in infertility workup. New analysis tools such as machine learning and cluster analysis can provide a more in-depth approach. Such explorative analyses have the potential to uncover hitherto hidden patterns in data that might be difficult to spot for andrologists but become visible by these tools. Study design, size, duration A Cluster analysis was retrospectively performed in a clinically well characterized cohort of 2742 men with unexplained or idiopathic male infertility. These men had visited our Centre within a 10-year period (2008-2018) for infertility workup. Due to the well curated database (Androbase®) we were able to include up to 37 andrologic parameters in the unbiased cluster analysis. Participants/materials, setting, methods After applying strict selection criteria 2742, of initially 7627, infertile men remained for cluster analysis (exclusion: obstructive -, genetic -, other causative factors, female factor; inclusion: azoo- to normozoospermia, FSH ≥ 1IU/l, Testosterone ≥ 8nmol/l). For subsequent analyses the following parameters were included: somatic/semen/hormone parameters, testicular sonography and testis volume, genotyping of the FSHB c.-211G>T (rs10835638) single nucleotide polymorphism. For cluster analysis, partitioning around medoids method was employed based on Gower distance between patients. Main results and the role of chance The applied cluster approach for the study population yielded two separate clusters (average silhouette width ∼0.12). These clusters showed significantly different distributions in bi-testicular volume, FSH and FSHB genotype. Cluster 1 contained all men homozygous for G (wildtype) in FSHB c.-211G>T (100%), while Cluster 2 contained most patients carrying a T allele (>96.6%). Even in subgroup analysis (Total sperm count (TSC) <1Mill and TSC 1³Mill) two clusters each were formed too. Again, the strongest segregation markers between the respective clusters were FSHB c.-211G>T, bitesticular volume, and FSH, supporting the notion of a contributing genetic factor. Surprisingly, sperm parameters like TSC, motility and morphology played a minor role in cluster formation; as well as testicular maldescent, varicocele, smoking, and microlithiasis testes. The genetic parameter of FSHB c.-211G>T in combination with the established parameters FSH and testicular volume should attract more attention in future clinical workups of infertile men with unknown etiologic factors. Limitations, reasons for caution Categorical and numeric features contribute diversely to the calculation of patient dissimilarity. Potentially, categorical features can have a higher impact because patients are rated as completely different if they fall in different categories; for numeric features, the dissimilarity depends on the range of values. Wider implications of the findings The FSHB SNP was identified as an informative segregation marker; we therefore suggest introducing diagnostic genotyping into clinical routine in men with so far idiopathic or unexplained male infertility. This may reduce the high number of infertile men with so far unknown origin by nearly one-third. Trial registration number DFG Clinical Research Unit 326 Male Germ Cells

Consultants’ attitudes to the ideal age for orchidopexy

Introduction Recent consensus statements recommend that orchidopexy for undescended testis is performed between 6 and 12 months of age. We designed a survey to determine what age consultant surgeons believe is the optimal age for orchidopexy as well as surveying other aspects of surgery for testicular maldescent. Methods An anonymous survey was distributed to 122 UK consultants who participated in an international prospective audit of orchidopexy outcomes. Preferences and management strategies were compared between different groups of surgeons (specialist paediatric general surgeons, specialist paediatric urologists and general surgeons/urologists with an interest in general surgery of childhood [but who mainly treat adult patients]). Results There were 105 responses (62 specialist paediatric surgeons, 30 specialist paediatric urologists and 13 general surgeons/urologists) from 25 centres. The overall response rate was 86%. The median preferred age for orchidopexy was 10.5 months (range: 3–24 months). This differed significantly between groups, with a median of 12 months among specialist paediatric surgeons, 9 months among specialist paediatric urologists and 12 months among general surgeons/urologists (p = 0.001). Fifty-one consultants (49%) stated that the optimal age to perform orchidopexy was twelve months or more. Respondents cited concerns about the possible long-term effects of general anaesthesia at a young age and higher atrophy rates in younger children as the main reasons for postponing orchidopexy until 12 months. Conclusions There remains no consensus among surgeons as to the optimal age for orchidopexy. Management practice of undescended testis varies across different surgical specialties, particularly with regard to optimal age of surgery.

Congenital abdominal wall defects and cryptorchidism: a population-based study

PurposeSeveral studies have reported high prevalence of undescended testis (UDT) among boys with congenital abdominal wall defects (AWD). Due to rarity of AWDs, however, true prevalence of testicular maldescent among these boys is not known. We conducted a national register study to determine the prevalence of UDT among Finnish males with an AWD.MethodsAll male infants with either gastroschisis or omphalocele born between Jan 1, 1998 and Dec 31, 2015 were identified in the Register of Congenital Malformations. The data on all performed operations were acquired from the Care Register for Health Care. The register data were examined for relevant UDT diagnosis and operation codes.ResultsWe identified 99 males with gastroschisis and 89 with omphalocele. UDT was diagnosed in 10 (10.1%) infants with gastroschisis and 22 (24.7%) with omphalocele. Majority of these required an operation; 8/99 (8.1%) gastroschisis and 19/89 (21.3%) omphalocele patients. UDT is more common among AWD patients than general population with the highest prevalence in omphalocele.ConclusionsCryptorchidism is more common among boys with an AWD than general population. Furthermore, omphalocele carries significantly higher risk of UDT and need for orchidopexy than gastroschisis. Due to high prevalence testicular maldescent, careful follow-up for UDT is recommended.

The G178A polymorphic variant of INSL3 may be linked to cryptorchidism among Egyptian pediatric cohort.

Cryptorchidism (CO) is a genital disorder of multifactorial etiology, with serious remote complications. Mutations in insulin-like 3 hormones (INSL3) G/A variant remain a matter of inquiry. We aimed to investigate the association between G178A-INSL3 polymorphism and undescended testis in a cohort of Egyptian children. In this study, a total of 160 children, including 80 cases with primary non-syndromic undescended testes and 80 healthy children with normal external genitalia as controls, both, were analyzed after detailed history, physical examination and imaging for mutations of G178A polymorphism of INSL3 gene by restriction fragment length polymorphism (RFLP) technique. We found most of the undescended testes were inside the inguinal canal mainly on the left side. Genetic analysis revealed thatthe mutant A allele of G178A INSL3 variant was significantly detected in the patient group with a frequency of 26.2% against 12.5% for control subjects, especially among cases with an evident family history of similar cases as shown by p value = 0.001 and odd's ratio (CI95%) of 0.13 (0.04-0.723). In conclusion, G178A-INSL3 gene polymorphism could be a susceptibility factor for testicular maldescent in Egyptian children. Also, family history of similar cases was considered as significant predictive risk for cryptorchidism, added to the shared genetic links to consanguinity in our locality.

Medical and neurobehavioural phenotypes in male and female carriers of Xp22.31 duplications in the UK Biobank.

Deletions spanning the STS (steroid sulfatase) gene at Xp22.31 are associated with X-linked ichthyosis, corneal opacities, testicular maldescent, cardiac arrhythmia, and higher rates of developmental and mood disorders/traits, possibly related to the smaller volume of some basal ganglia structures. The consequences of duplication of the same genomic region have not been systematically assessed in large or adult samples, although evidence from case reports/series has indicated high rates of developmental phenotypes. We compared multiple measures of physical and mental health, cognition and neuroanatomy in male (n = 414) and female (n = 938) carriers of 0.8–2.5 Mb duplications spanning STS, and non-carrier male (n = 192, 826) and female (n = 227, 235) controls from the UK Biobank (recruited aged 40–69 from the UK general population). Clinical and self-reported diagnoses indicated a higher prevalence of inguinal hernia and mania/bipolar disorder respectively in male duplication carriers, and a higher prevalence of gastro-oesophageal reflux disease and blistering/desquamating skin disorder respectively in female duplication carriers; duplication carriers also exhibited reductions in several depression-related measures, and greater happiness. Cognitive function and academic achievement did not differ between comparison groups. Neuroanatomical analysis suggested greater lateral ventricle and putamen volume in duplication carriers. In conclusion, Xp22.31 duplications appear largely benign, but could slightly increase the likelihood of specific phenotypes (although results were only nominally-significant). In contrast to deletions, duplications might protect against depressive symptoms, possibly via higher STS expression/activity (resulting in elevated endogenous free steroid levels), and through contributing towards an enlarged putamen volume. These results should enable better genetic counselling of individuals with Xp22.31 microduplications.

Outcomes in Patients with Testicular Maldescent and Germ Cell Neoplasia: A Retrospective Assessment and Review of the Literature

Outcomes in Patients with Testicular Maldescent and Germ Cell Neoplasia: A Retrospective Assessment and Review of the Literature

Perineal Ectopic Testis in an Adult

Testicular maldescent may be cryptorchid with descent being arrested along its normal pathway resulting in an abdominal, inguinal or high scrotal testis, or it may stray from the normal descent to settle in an ectopic site outside the scrotum; such as the perineum, pubic region, dorsum of the penis, femoral region, anterior abdominal wall and the contralateral scrotum. Management is orchidopexy through an inguinal crease incision as the length of the spermatic cord is normal. We report a 26 year old man with a left perineal testis who underwent orchidopexy as the testicular volume was normal.Key words: Ectopic testis, Perineal testis,Maldescended testis

Perineal Ectopic Testis in an Adult

Testicular maldescent may be cryptorchid with descent being arrested along its normal pathway resulting in an abdominal, inguinal or high scrotal testis, or it may stray from the normal descent to settle in an ectopic site outside the scrotum; such as the perineum, pubic region, dorsum of the penis, femoral region, anterior abdominal wall and the contralateral scrotum. Management is orchidopexy through an inguinal crease incision as the length of the spermatic cord is normal. We report a 26 year old man with a left perineal testis who underwent orchidopexy as the testicular volume was normal.Key words: Ectopic testis, Perineal testis,Maldescended testis

Diethylstilbestrol Regulates the Expression of LGR8 in Mouse Gubernaculum Testis Cells.

BackgroundHormonal effects on the gubernaculum can affect testicular descent. Diethylstilbestrol (DES) is a nonsteroidal synthetic estrogen that disrupts the outgrowth of gubernaculums, leading to testis maldescent. However, the underlying mechanisms remain elusive.Material/MethodsThe gubernaculum were removed from 3-day-old mice and cultured. The subcultured cells were randomly divided into a normal control group and experimental groups. The DES groups were administered 10 μg/ml, 1 μg/ml, 0.1 μg/ml, 0.01 μg/ml of diethylstilbestrol dissolved in dimethyl sulfoxide (DMSO) respectively. The cell morphology was observed under an inverted microscope, and leucine-rich repeat-containing G protein-coupled receptor 8 (LGR8) was localized by immunofluorescence. The expressions of LGR8 gene and protein in gubernaculum cells were quantified by RT-PCR and Flow Cytometer respectively.ResultsDES treatment converted cells from a normal fibroblast-like morphology into a more refractile, spindle-shaped morphology or irregular elliptical shapes along with cytoplasmic shrinkage. LGR8 was expressed in the cytoplasmic membrane, DES dose-dependently downregulated LGR8 expression at low doses (≤1.0 μg/ml), but upregulated LGR8 at high doses (10 μg/ml) at both the mRNA and protein levels.ConclusionsThese results suggest that DES causes testicular maldescent by altering the LGR8 pathway in mouse gubernaculum testis cells.

Transverse testicular ectopia in adults: A case series

Introduction: transverse testicular ectopia (ttE) or transverse aberrant testicular maldescent is a rare clinical entity where both testes descend into one side of scrotum. the patients having ttE often present with ipsilateral inguinal hernia associated with migrated ectopic testis and contralateral empty hemiscrotum and nonpalpable testis. case series: We are reporting two cases of a rare testicular descent anomaly where both patients presented with unilateral inguinal hernia with contralateral non-palpable testis and were diagnosed as transverse testicular ectopia intraoperatively. On examination, two separate cords were found to be coming out from same inguinal canal. there were no cord anomalies or remnant of Mullerian duct. In both of the cases inguinal hernia repair with orchiopexy was done. conclusion: In a patient with unilateral inguinal hernia and contralateral absent testis, a strong suspicion of ttE should be kept and

The management of the persistent Müllerian duct syndrome

ObjectivesTo report the findings and management of patients with persistent Müllerian duct syndrome (PMDS). Patients and methodsNineteen phenotypically male patients (aged 8months to 27years) presented with testicular maldescent. All of them had normal male external genitalia. Two of them had had a previous diagnosis of persistent Müllerian structures. All patients were karyotyped, and had a hormonal profile, diagnostic laparoscopy, retrograde urethrocystogram, gonadal biopsies, and surgical management according to the findings. The follow-up was based on a clinical examination, abdominal ultrasonography (US) and scrotal colour-Doppler US at 3 and 6months after surgery, and every 6months thereafter. ResultsDiagnostic laparoscopy showed the presence of persistent Müllerian structures in all 19 patients. All patients had a normal male karyotype (46XY). Ten patients had a laparoscopic excision of their Müllerian structures while the remaining nine patients had their Müllerian structures left in place. No malignant changes were found in the excised Müllerian tissues. Of the 37 gonadal biopsies taken, 31 (84%) indicated normal testes. ConclusionsThe incidence and prevalence of PMDS are not well estimated. Müllerian structures should be removed whenever possible to avoid the risk of malignant transformation. The early diagnosis of PMDS makes possible the excision of Müllerian structures and a primary orchidopexy. A long-term follow-up is needed for patients with intact Müllerian structures and magnetic resonance imaging might be a better method than US for that purpose. Most of the patients had normal testicular histology, which might allow fertility.

Genetic analysis of the human Insulin-like 3 gene: absence of mutations in a Greek paediatric cohort with testicular maldescent.

This study investigated the hypothesis that genetic alterations of the human insulin-like 3 (INSL3) gene are associated with testicular maldescent (TMD). Genomic DNA was extracted and amplified from peripheral blood samples of 170 unrelated children with all possible phenotypical expressions of TMD and 50 volunteers with normal external genitalia from the general paediatric population (controls). PCR-single strand conformation polymorphism analysis was used to screen INSL3 gene for genetic variants. For rapid screening of a detected nonsilent genetic alteration, restriction assay using endonuclease Eag I was further employed. Products were analysed on 2% agarose gel and restriction patterns were visualised by ethidium bromide. Differences in genotype and allelic distributions of nonsilent genetic alterations were evaluated between (i) patients-controls, (ii) familial-sporadic, (iii) bilateral-unilateral and (iv) intra-abdominal-inguinal cases of TMD. No mutations were detected. Three common INSL3 gene polymorphisms (27G>A, 126G>A, 178G>A) unrelated to any particular phenotype of TMD were detected both in patients and controls. These results indicate that INSL3 gene mutations are not a common cause of TMD in the human.

The Relation between Adult Dark Spermatogonia and Other Parameters of Fertility Potential in Cryptorchid Testes

The fertility potential of boys with cryptorchidism may be related to the number of adult dark spermatogonia per tubular transverse section in testicular biopsies taken at orchiopexy. Placental-like alkaline phosphatase positive gonocytes in testes within year 1 of life indicate preserved ability for germ cell transformation. We related these parameters to the total number of tubular germ cells and other factors associated with fertility potential. The study comprised 89 boys 0.7 to 3 years old (median age 1.8) who underwent bilateral testicular biopsy at bilateral orchiopexy and provided blood samples for gonadotropins and inhibin B. Of 76 boys with adult dark spermatogonia 44 (58%) had a normal mean number of spermatogonia per tubular transverse section compared to 2 of 13 (15%) without adult dark spermatogonia (p <0.05). In the 30 boys with good fertility potential, including a normal mean number of tubular germ cells, and normal gonadotropins and inhibin B, the mean number of adult dark tubular germ cells was 0.081 vs 0.031 in the 38 with low fertility potential, including impaired tubular germ cells and/or low inhibin B but no reactive increase in gonadotropins (p <0.05). In the 21 patients with increased gonadotropins the mean number of adult dark spermatogonia per tubular transverse section was 0.063. Of the 20 boys with normal mean adult dark spermatogonia per tubular transverse section 12 (60%) had good fertility potential, including a normal mean number of tubular germ cells, normal gonadotropins and normal inhibin B, compared to only 18 of 69 (26%) with an impaired mean number of adult dark spermatogonia per tubular transverse section (p <0.05). Of 46 boys with a normal mean number of tubular germ cells 26 (57%) had placental-like alkaline phosphatase positive cells compared to 14 of 43 (33%) with a decreased mean number of tubular germ cells (p <0.05). The number of placental-like alkaline phosphatase positive gonocytes and adult dark spermatogonia per tubular transverse section are important parameters related to the fertility potential of boys with cryptorchid testes.

Screening for Y chromosome microdeletions in childhood: lack of evidence for a direct association with testicular maldescent

The aim of the study was to investigate the hypothesis that Y chromosome microdeletions are directly implicated in testicular maldescent. Genomic DNA was extracted from the peripheral blood of 292 subjects. This population consisted of (i) 180 children with all phenotypes of isolated (non-syndromic) testicular maldescent from 174 index families, (ii) affected adult relatives available (n=12) and (iii) 100 unrelated children with normal external genitalia (controls). The sequence-tagged site primer set and the conditions of conventional polymerase chain reaction amplification were based on the current laboratory guidelines for molecular diagnosis of Y chromosome microdeletions recommended by the European Academy of Andrology and the European Molecular Genetics Quality Network. Two multiplex reactions were designed to screen the regions of azoospermic factors a, b and c. Each multiplex reaction included adequate internal and external amplification controls. Amplification products were submitted to electrophoresis on 2% agarose gel impregnated with ethidium bromide dye solution for 80 volt-h and visualised under ultraviolet light. No microdeletions were detected in any subject. These results indicate that Y chromosome microdeletions are not directly implicated in the pathogenesis of testicular maldescent. Other factors should be investigated to potentially explain the genetic predisposition that seems to exist in at least a subgroup of these patients.

The (TAAAA)npolymorphism of sex hormone-binding globulin gene is not associated with testicular maldescent

The aim of this family-based study was to investigate the potential association/genetic linkage of the (TAAAA)n polymorphism of sex hormone-binding globulin gene proximal promoter with testicular maldescent (TMD). Genomic DNA was extracted from the peripheral blood of 487 subjects (174 index families): (i) 180 children with all phenotypes of TMD, (ii) 307 parents (156 mothers and 151 fathers). Conventional polymerase chain reaction amplification products were electrophoresed on 10% nondenaturating polyacrylamide gel and visualised by silver staining. After excluding ambiguous parental-child trios and most cases of index families with missing parental genotypes, 429 individuals were left for analysis: 138 completely typed nuclear families (five included a second affected child) and five child-parent couples (one parent missing). Eight fathers presented history of TMD, that is, a total of 156 cases with TMD were analysed. Alleles were analysed with the affected family-based control method and logistic regression-based extension of the transmission disequilibrium test for multiallelic loci. (ΤΑΑΑΑ)n polymorphism analysis revealed six alleles based on repeat numbers (n=5-10). No association/genetic linkage between the (TAAAA)n polymorphism and TMD was detected. Other factors should be investigated to potentially explain the genetic predisposition that seems to exist in at least a subgroup of these patients.

Associations between congenital cryptorchidism in newborn boys and levels of dioxins and PCBs in placenta

In animal studies, exposure to dioxins has been associated with disrupted development of the male reproductive system, including testicular maldescent. Some polychlorinated biphenyls (PCBs) have also dioxin-like effects. In addition, one previous case–control study has reported an association between congenital cryptorchidism and colostrum PCB levels. We performed a case–control study to evaluate whether congenital cryptorchidism in boys was associated with increased levels of dioxins or PCBs in placenta reflecting foetal exposure. In addition, associations between placenta levels of these chemicals and reproductive hormone levels in boys at 3 months were studied. Placentas were collected in a Danish–Finnish joint prospective cohort study on cryptorchidism (1997–2001). The boys were examined for cryptorchidism at birth and at 3 months. Altogether, 280 placentas [112 Finnish (56 cases, 56 controls) and 168 Danish (39 cases, 129 controls)] were analysed for 17 toxic polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and 37 PCBs (including 12 dioxin-like PCBs). Infant serum samples taken at 3 months were analysed for reproductive hormones. No significant differences between cases and controls were observed in either country in dioxin WHO-TEq levels (median 9.78 vs. 8.47 pg/g fat, respectively, in Finland, and 11.75 vs. 10.88 pg/g fat in Denmark) or PCB WHO-TEq levels (median 2.12 vs. 2.15 pg/g fat in Finland, 2.34 vs. 2.10 pg/g fat in Denmark) or total-TEq levels (median 11.66 vs. 10.58 pg/g fat in Finland, 13.94 vs. 13.00 pg/g fat in Denmark). Placenta WHO-TEq levels of dioxins were not associated with infant reproductive hormone levels at 3 months. In Finland, PCB WHO-TEq levels in placenta associated positively with infant LH levels. WHO-TEq levels of dioxins and PCBs and total-TEq levels were higher in Danish than Finnish samples. In conclusion, no association between placenta levels of dioxins or PCBs and congenital cryptorchidism was found. Significant country differences in chemical levels were observed.

ESR1 promoter polymorphism is not associated with nonsyndromic cryptorchidism

The ESR1 promoter microsatellite (TA)n was reported as a potential functional polymorphism. In a case-control study, we were unable to demonstrate any association between (TA)n and nonsyndromic cryptorchidism in Italian and Spanish study populations.

Further insights into the role of T222P variant of RXFP2 in non-syndromic cryptorchidism in two Mediterranean populations

The aetiopathogenesis of isolated cryptorchidism remains largely unknown. Mutation screenings in the most relevant candidate genes for testicular maldescent lead to controversial data in the literature. In particular, the role of the T222P genetic variant of the RXFP2 gene is still debated. Given the controversies, the aim of this study was to provide further data on this genetic variant in two Mediterranean populations. A total of 577 subjects from Spain and 550 from Italy (with and without a history of cryptorchidism) were analysed. The T222P substitution was found in both unilateral and bilateral cases and in a total of 12 controls. These data exclude a clear-cut cause-effect relationship between T222P variant and testicular maldescent. The T222P variant was found at a similar frequency in both cases and controls in the Spanish population, whereas in Italy, the frequency of T222P resulted significantly higher in the cryptorchid group (p = 0.031). The observed difference between the two countries and the highly variable phenotypic expression of the T222P variant may depend on the genetic background or on environmental conditions. The haplotype analysis of the RXFP2 gene in T222P carriers and their parents showed that this variant is linked to the previously inferred C-C-G-A-13 haplotype and consequently provides further support to the 'founder effect' hypothesis. In conclusion, our data indicate that T222P is a frequent variant in the Spanish population with no pathogenic effect. Although in Italy it seems to confer a mild risk (odds ratio = 3.17, 95% confidence interval: 1.07-9.34) to cryptorchidism, the screening for this variant for diagnostic purposes is not advised because of the relatively high frequency of control carriers (1.4% of Italian men without a history of cryptorchidism).

Characteristics of cryptic/ectopic and contralateral scrotal testes in dogs between 1 and 2 years of age

Testicular malposition represents a common developmental genital defect in dogs and can affect one or both testes. In both humans and dogs, unilateral cryptorchism is more frequently detected and thought to be the expression of a genetic abnormality affecting both the undescended and scrotal testis. In the dog, there is evidence of degenerative processes affecting the maldescended testis. However, the histologic and functional changes that occur in the scrotal testis of unilateral cryptorchid or ectopic individuals remain a source of debate. Because the bilateral surgical removal of the testes leads to some undesirable side effects, the aim of this study was to evaluate the necessity for performing bilateral orchiectomy in young unilateral cryptorchid dogs. A morphologic study of both cryptic/ectopic and scrotal testes in young dogs affected by unilateral testicular maldescent was therefore conducted. The study was conducted on 10 dogs aged 1 to 2 yr and affected by unilateral testicular maldescent. We found that, in young dogs, even if no neoplastic lesions were observed, morphologic abnormalities are detectable between 1 and 2 yr of age in the maldescended testes with severity dependent on testicular position. In contrast, in the scrotal testes, the histologic and immunohistochemical exam failed to find signs of incorrect development or morphologic abnormalities. The results seem to suggest that, though the early removal of the undescended testis is recommended, continuous monitoring of the scrotal testis for the life of the dog is preferable to removing it considering the undesirable side effects related to castration.