Search Results (96)

Hypospadias is a congenital malformation of the male external genitalia resulting from incomplete fusion of the urethral folds during embryonic development. The perineal form represents the most severe phenotype and is frequently associated with abnormalities such as cryptorchidism and penile hypoplasia. Although surgical correction is generally recommended in young dogs, the long-term clinical course of severe hypospadias under conservative management remains poorly documented. In this study, we describe an unusual canine case of severe perineal hypospadias that survived to geriatric age under conservative management and subsequently developed bilateral testicular tumors arising from cryptorchid testes. Despite recurrent urinary tract infections during early life, the patient maintained an acceptable quality of life with long-term supportive care, providing a rare clinical example of extended survival without surgical correction. Because no molecular material was available from the patient, publicly available mouse transcriptomic datasets related to genital tubercle development and Leydig cell differentiation were consulted only as contextual reference. These datasets illustrate established developmental regulators and steroidogenic pathways relevant to genital formation and testicular function but do not represent direct molecular findings from the reported case. This report primarily highlights the clinical course and management of severe hypospadias in a dog, while using existing transcriptomic knowledge solely to provide biological context. The findings should therefore be interpreted as descriptive and hypothesis-generating rather than as evidence of a direct mechanistic link between developmental abnormalities and endocrine tumorigenesis. Full article

Congenital anomalies of the reproductive system represent a heterogeneous group of structural and functional abnormalities affecting both male and female genital organs. These anomalies typically arise during embryogenesis and may remain asymptomatic until they are incidentally identified during evaluation for infertility, recurrent pregnancy loss, or disorders of sexual development. In females, abnormalities include Müllerian duct anomalies and congenital malformations of the uterus, cervix, vagina, and ovaries, such as Mayer–Rokitansky–Küster–Hauser syndrome, septate, unicornuate, bicornuate, and didelphys uteri, and ovarian agenesis and undescended ovaries. In males, congenital conditions such as anorchia, cryptorchidism, hypospadias, ejaculatory duct obstruction, and ejaculatory dysfunction may be associated with impaired spermatogenesis and reduced fertility. Early recognition of these conditions may facilitate timely clinical evaluation and individualized management, which can include surgical correction, hormonal therapy, and reproductive counseling. When appropriate, early diagnosis may support multidisciplinary care, with the aim of optimizing sexual development, preserving reproductive potential, and reducing long-term morbidity associated with congenital anomalies. However, the clinical impact of early detection varies depending on the type and severity of the anomaly. A systematic and multidisciplinary approach may contribute to improved reproductive outcomes and better overall reproductive health in affected individuals. Further research is needed to better define the optimal timing and clinical utility of systematic evaluation strategies in this patient population. Full article

Cryptorchidism is the most common non-lethal congenital defect of the male reproductive system in sheep, with potential economic consequences for flock management. This study investigated the incidence, testicular morphology, ultrasonographic characteristics, semen quality, and sexual behavior of bilateral cryptorchid Sarda rams. Slaughterhouse inspections of 2360 lambs showed an incidence of 0.87% cryptorchidism. Cryptorchid testes were significantly rounder and lighter than intact testes, indicating impaired development in affected animals. Ultrasonography of 15 adult bilateral cryptorchid rams showed that retained testes were markedly undersized and that the left testis was less frequently visualized. No significant association with age was detected within the studied age range. All ejaculates recovered from bilateral cryptorchid rams were azoospermic. Nevertheless, behavioral trials suggested that bilateral cryptorchid males retained sexual interest and the ability to identify estrous ewes. These findings confirm the infertility of bilateral cryptorchid Sarda rams while highlighting their preserved sexual behavior, suggesting a potential zootechnical use as teaser rams for heat detection. Repurposing cryptorchid males in this way could represent a potential alternative to surgically modified teaser rams or the use of aprons on intact rams. Full article

Background/Objectives: Cryptorchidism is a common cause of male infertility and often results in azoospermia. However, the metabolic perturbations underlying cryptorchidism complicated with azoospermia and their association with surgical sperm retrieval outcomes remain poorly defined. Methods: A total of 35 patients with cryptorchidism and azoospermia, as well as 40 controls with normal semen parameters, were enrolled in the study. Seminal plasma samples from all participants were subjected to metabolomic analysis. Additionally, some patients underwent micro-TESE; the association between metabolomic features and the success or failure of surgical sperm retrieval was further analyzed. Results: A total of 931 differential metabolites were identified between patients and controls, primarily enriched in lipid metabolism and amino acid metabolism pathways. Lipid metabolites were broadly downregulated in patients, while several inflammation-related metabolites, including Prostaglandin E2, were upregulated. Routine clinical parameters showed no significant differences between patients with successful and failed micro-TESE. However, metabolomic profiles effectively distinguished these two subgroups. These differential metabolites between the two subgroups were mainly involved in three key pathways: phenylalanine–tyrosine–tryptophan biosynthesis, aminoacyl-tRNA biosynthesis, and folate biosynthesis. Most metabolites in the first two pathways were downregulated in the successful retrieval group, while those in the folate biosynthesis pathway showed the opposite regulatory trend. Four metabolites, including Leucine, 7,8-Dihydroneopterin, L-Tyrosine and Pterin, exhibited robust predictive value for micro-TESE outcomes. Conclusions: This study reveals distinct metabolic signatures in patients of cryptorchidism with azoospermia. The identified metabolic biomarkers provide valuable references for clinical decision-making regarding micro-TESE, facilitating a personalized assessment of sperm retrieval feasibility. Full article

Introduction/Purpose: Congenital cryptorchidism and retractile testis represent the most commonly presented abnormalities of the male genitourinary system. Orchiopexy is the surgical treatment for both conditions and can be performed either via the conventional two-incision surgical approach or via a singular scrotal incision. The present study firstly investigated the complications associated with each orchiopexy approach in a single-center pediatric surgical department and secondly compared the surgical outcomes in children with congenital cryptorchidism or retractile testes. Methodology: A retrospective analysis was conducted in pediatric patients with either congenital cryptorchidism or retractile testes who underwent orchiopexy from 2015 to 2019. Data collected during the study included diagnosis, surgical technique and both short- and long-term complications. Patient stratification was performed in accordance with the type of orchiopexy and the diagnosis UDT vs. RT and inguinal orchidopexy vs. scrotal orchidopexy. Results: A total of 362 children underwent 443 orchiopexies of which 227 were inguinal and 216 were scrotal. Complications were reported in 16 (3.6%) surgeries and from which 14 (3.16%) were presented in for postoperative complications. Short-term complications were presented in four (0.9%) cases and consisted of wound dehiscence. Long-term complications were recorded in 12 (2.7%) cases, including recurrence in six (1.3%) testes, testicular atrophy in three (0.6%) cases and presentation of hydrocele or inguinal hernia in two (0.4%) and one (0.2%) patient, respectively. Notably, 13 orchidopexies with preoperative diagnosis of congenital cryptorchidism, were linked with complications (p = 0.01), 12 of which underwent with two-incision technique (p = 0.07). Conclusions: The findings of the study suggest that a preoperative diagnosis of congenital cryptorchidism is a possible risk factor for postoperative complications. With regard to the surgical technique performed, the single-incision scrotal orchiopexy appears to be a much safer and more effective approach palpable undescended testes, compared to the two-incision approach. For the high-lying testes, although the single-scrotal technique provides good results, more prospective studies with selected impalpable undescended testes are needed to strengthen the existing literature. Full article

Background: Mini-puberty is a transient but critical postnatal activation of the hypothalamic–pituitary–gonadal axis, essential for male gonadal maturation, penile and testicular growth, and future reproductive potential: this physiological hormonal surge is absent or blunted in congenital hypogonadotropic hypogonadism (CHH), often manifesting as micropenis, cryptorchidism, and impaired Sertoli cell proliferation. Objective: The aim of this review is to summarize current evidence on the impact of early gonadotropin therapy in male infants with CHH. Methods: We conducted a comprehensive literature review using PubMed, including studies reporting on male infants with confirmed or suspected CHH receiving gonadotropin therapy. Keywords included “mini-puberty and hypogonadism”, “gonadotropins and infancy,” and “gonadotropin therapy in CHH.” Eligible studies reported biochemical outcomes (luteinizing hormone, follicle-stimulating hormone, testosterone, inhibin B, anti-Müllerian hormone) and clinical measures (penile length, testicular volume, testicular descent). Data extraction focused on endocrine responses, genital growth, and safety. Results: Twelve studies including 95 infants were analyzed. Early gonadotropin therapy effectively restored postnatal hormonal levels, with consistent increases in testosterone, inhibin B, and anti-Müllerian hormone. Clinically, treatment induced significant penile growth, increased testicular volume and partial or complete testicular descent in the majority of cases. Both continuous infusion and intermittent injection regimens were effective, though hormone kinetics and growth responses varied. No serious adverse events were reported, and therapy was generally well tolerated. Conclusions: Early gonadotropin therapy during mini-puberty represents a safe and effective intervention to replicate the physiological postnatal hormonal surge in male infants with CHH. Prospective longitudinal studies are warranted to evaluate sustained effects on puberty, fertility, and adult reproductive function. Full article

Background: Testicular dysgenesis syndrome (TDS) is a complex disorder of the male reproductive system related to disfunction of the fetal testis. The clinical features of TDS may be evident at birth or infancy (cryptorchidism, hypospadias and/or reduced anogenital distance) or occur later in adulthood (testis cancer, infertility). Genetic background seems to be important for genetic predisposition, with new genes being associated with components of the syndrome in last years. Interestingly, the incidence of clinical manifestations of TDS has been increasing in many countries in recent decades, suggesting that genetic predisposition alone cannot explain this trend. Consequently, the hypothesis of multifactorial etiopathogenesis is becoming increasingly accepted nowadays, with environmental factors probably acting during early developmental stages in genetically predisposed individuals. Methods: In this narrative review, we aim to critically evaluate genetic and non-genetic factors involved in the pathogenesis of TDs. Results: Important associations with intrauterine growth disorders and maternal diseases (overweight/obesity and diabetes) as well as lifestyle factors (e.g., smoking and alcohol abuse) were found. In such context, endocrine disruptors probably play a major role. These substances are widely used in industry and can exert estrogenic and antiandrogenic effects, potentially interfering with the development of the fetal gonad. Conclusions: Considering their possible impact on male sexual health, more attention should be focused on maternal modifiable factors to confirm with prospective studies the mixed results of available evidence. Full article

Cryptorchidism is a genital defect in which ram testicles fail to descend, causing azoospermia, while maintaining normal behavior towards females. We investigated whether cryptorchid rams can induce a ram-effect in ewes that would then be subjected to artificial insemination (AI). Therefore, ewes were isolated from any contact with rams for 6 weeks, then exposed to cryptorchid rams for 14 days. From day 15 to day 24, estrus was checked using a cryptorchid teaser four times daily (at 08:00, 12:00, 16:00, 20:00). Ewes detected in estrus were inseminated 24 h later. Experiment 1 included ewes (n = 31) all exposed to the cryptorchid ram-effect (CRE): 70.9% showed estrus, lambing rate after AI was 45.5%, and prolificacy was 1.40. Experiment 2 compared CRE (n = 80) with a control group with no prior exposure to males (n = 39). Estrus occurrence differed significantly (75.0% vs. 23.1%, respectively, p ≤ 0.001). Lambing rate from AI was 44.1% and prolificacy 1.27. These results show that cryptorchid rams effectively induce and synchronize estrus in Sarda ewes. AI fertility results on natural estrus following CRE yields outcomes comparable to those previously reported after hormonal synchronization for this breed. Full article

Background/Objectives: Undescended testis (UT) is a common congenital urological condition in boys, with an incidence of 2–8%. Orchiopexy is the recommended surgical treatment for UT, ideally performed before 12 months of age, with a latest window of 18 months. Testicular torsion (TT) is a pediatric urological emergency, occurring in 3.8 per 100,000 boys. While both UT and TT are common conditions individually, their co-occurrence in children under 18 months is rare and represents a challenging clinical scenario, especially when diagnosis and treatment are delayed, increasing the risk of testicular necrosis. Methods: This report describes two cases of testicular torsion in undescended testes in infants under 1 year of age. Both patients were presented to the hospital more than 24 h after symptom onset. Such delay led to the possibility of testicular salvage being lost due to necrosis. The first case involved a 10-month-old infant with bilateral undescended testis, who underwent orchiectomy after 36 h of torsion. The second case involved a 7-month-old baby, where a delayed diagnosis led to orchiectomy following 36 h of torsion. Both children were previously on the waiting list for orchiopexy, and in both cases contralateral orchiopexy was performed. A review of the literature on PubMed using the key-words “cryptorchid”, “undescended testis”, and “testicular torsion” revealed 36 cases of UT complicated by TT in children under 18 months, showing a high incidence of orchiectomies due to delayed diagnosis. Conclusions: Testicular torsion in undescended testis in children under 18 months is rare but associated with a high risk of gonadal necrosis. The key to improving testicular salvage rates is timely diagnosis and intervention, ideally within 6 h of symptom onset. Delayed presentation due to atypical clinical signs, such as inguinal swelling or nonspecific symptoms, complicates early detection and thus testicular salvage. Therefore, it is crucial for both parents and pediatricians to recognize the potential for torsion in cryptorchidic patients, emphasizing the importance of early surgical intervention, including orchiopexy, to prevent torsion and its associated complications. Full article

Cryptorchidism, characterized by undescended testes, is associated with infertility and increased cancer risk through complex, multifactorial pathophysiological mechanisms involving interconnected alterations in testicular microenvironment, including but not limited to elevated temperature, hormonal dysregulation, altered vascular perfusion, and immune responses. These factors interact synergistically to drive testicular pathology. Using a surgically induced bilateral cryptorchid mouse model established at postnatal day 21 (PND21), we investigated phase-specific pathological mechanisms through analyses at prepubertal (PND35) and sexually mature (PND70) phases. Our transcriptome analysis revealed distinct molecular signatures at different developmental phases, with prepubertal cryptorchid testes showing 2570 differentially expressed genes predominantly enriched in immunoproteasome components and inflammatory pathways, while sexually mature testes exhibited 883 differentially expressed genes primarily related to extracellular matrix (ECM) remodeling and oncogenic pathways. Prepubertal molecular changes indicated immunoproteasome activation and inflammatory responses, whereas mature-phase alterations were characterized by ECM reorganization and fibrotic remodeling. Functional analysis demonstrated prepubertal enrichment in spermatogenesis regulation and interferon responses, while mature-phase signatures were associated with apoptosis, epithelial–mesenchymal transition, and inflammatory signaling cascades. Phase-specific oncogenic pathway correlations revealed distinct mechanisms: metabolic reprogramming and epigenetic regulation in prepubertal testes versus structural remodeling and invasion-related pathways in mature testes. Molecular validation confirmed elevated PI3K-Akt and NF-κB signaling at both developmental phases, identifying these as potential therapeutic targets. This first phase-resolved characterization of cryptorchidism pathology provides insights into developmental phase-specific mechanisms and suggests timing-dependent therapeutic strategies. Although differing from human congenital cryptorchidism in developmental timing and etiology, our surgically induced model recapitulates anatomical testicular malposition with multiple inseparable pathophysiological alterations, and the identified molecular signatures reflect integrated responses to the complex cryptorchid microenvironment. Full article

Approximately 7% of males globally suffer from male infertility, which is becoming more widely acknowledged as a clinical indicator of potential health hazards as well as a cause of reproductive failure. Among these, cancer has become a significant worry due to mounting evidence that spermatogenesis impairment is associated with increased risk of prostate, testicular, and other cancers. Male infertility may be an early clinical manifestation of systemic genomic instability due to shared biological pathways, such as Y-chromosome microdeletions (AZF regions), germline DNA repair defects, mutations in tumor suppressor genes (e.g., BRCA1/2, TP53), mismatch repair gene mutations (e.g., MLH1, MSH2), and dysregulated epigenetic profiles. This narrative review covers the most recent research on prognostic markers of cancer in infertile men. These include molecular biomarkers such as genetic, epigenetic, and proteomic signatures; endocrine and hormonal profiles; and clinical predictors such as azoospermia, severe oligozoospermia, and a history of cryptorchidism. The possibility of incorporating these indicators into risk stratification models for precision medicine and early cancer surveillance is highlighted. For this high-risk group, bridging the domains of andrology and oncology may allow for better counseling, earlier detection, and focused therapies. Full article

The growing interest in improving the fertility-rate of livestock species, considering their high economic value, has prompted the development of new methodological approaches using male germline stem cells. Spermatogonial stem cells’ (SSCs) potential to self-renew and differentiate into mature spermatozoa holds promise for their transplantation into testicular tissue and use in new biotechnological methodologies. Moreover, SSCs’ ability to convey genetic information to the next generation is a property that could be exploited for gene targeting. The review provides an update on the main aspects of SSC biology, focusing on the genetic regulators of self-renewal and differentiation processes and different isolation methods. In addition, recent advancement in the cryopreservation of SSCs from domestic animals and their transplantation into recipients’ testes are also discussed. Finally, a section focused on canine SSCs (cSSCs), their biological aspects, and their potential clinical application in the field of reproduction is included. This represents an effective animal model for human reproduction, development, and disease, given that the reproductive anatomy and physiology of canine species and human are similar. We then report on the potential clinical transplantation of SSCs into recipient testicular tissue and suggest future topics to explore for significant advances in fertility preservation. Full article

Background: Noonan syndrome (NS) is a genetically heterogeneous condition within the RASopathies spectrum, with distinctive craniofacial features, congenital heart defects, short stature, and variably present developmental delay. Most cases result from variants in genes regulating the RAS/MAPK pathway, with PTPN11 variants being the most frequent; the c.922A>G substitution being among the most commonly reported. Methods: This pilot study analyzed clinical and partial genetic features of NS in a cohort from Transylvania, evaluated in the Children’s Emergency Clinical Hospital in Cluj-Napoca. Thirty-one patients fulfilling the Van der Burgt diagnostic criteria (twenty-two males, nine females) were included. Clinical data were systematically reviewed, and targeted molecular testing for the PTPN11 c.922A>G variant was performed. Results: Congenital heart defects were highly prevalent, with pulmonary stenosis representing the most frequent anomaly (54.8%). Craniofacial dysmorphism was observed in 76.7% of cases, cryptorchidism in 50% of the males, and short stature below the third percentile was described in 77.4% of patients. Genetic screening identified the PTPN11 c.922A>G variant in two individuals (6.45%). Additional diagnoses included Williams–Beuren syndrome and a 17q11.2 deletion consistent with Neurofibromatosis–Noonan syndrome, underscoring the clinical and genetic heterogeneity of the cohort. Comparison with international reports highlighted variability in phenotype and variant frequency. Future research directions include Sanger sequencing of key PTPN11 exons and the application of next-generation sequencing targeting all RAS pathway genes. Conclusions: This is the first Romanian cohort study on patients with a clinical suspicion of NS, providing insight into their evaluation. The findings reinforce the need for comprehensive molecular approaches, facilitating diagnostic precision and counseling strategies. Full article

Cryptorchidism in piglets, characterized by undescended testicles, causes economic losses and reduces consumer acceptance. Hyperprolific sows (HPS) have been hypothesized to produce a higher incidence of cryptorchid offspring. This study investigated the incidence of cryptorchidism in piglets born to HPS and its association with piglet birth weight and litter size in an observational study. Data from 276 litters (144 Landrace × Yorkshire sows; 4003 piglets) were analyzed. Sows were classified by genetic line (conventional: 68 litters; HPS: 208 litters) and parity (primiparous: 144; second parity: 132). At first parity, all gilts were inseminated with semen from a phenotypically unilateral cryptorchid Duroc boar, whereas at second parity, semen from three normal Duroc boars, which were full siblings, was used. The Landrace × Yorkshire HPS line produced more piglets per litter than the conventional Landrace × Yorkshire line (16.5 ± 0.3 vs. 12.4 ± 0.6; p < 0.001). Cryptorchidism occurred in 25.7% (37/144) of litters inseminated with semen from the cryptorchid boar, compared with 3.8% (5/132) of litters inseminated with semen from normal boars (p < 0.001). In total, 42 sows produced at least one cryptorchid piglet across both parities. Among affected sows (n = 42), the average number of cryptorchid piglets per litter was 1.3 ± 0.6 (range: 1–3). In the HPS line, cryptorchidism was detected in 24.1% (26/108) of litters, compared with 30.6% (11/36) in the conventional line (p = 0.441). HPS piglets had lower birth weights than conventional piglets (1.14 ± 0.01 vs. 1.30 ± 0.02 kg; p < 0.001). In the HPS line, litters with cryptorchid piglets had lower birth weights than those without (1.11 ± 0.02 vs. 1.18 ± 0.01 kg; p = 0.012), whereas no difference was observed in the conventional line (1.31 ± 0.04 vs. 1.28 ± 0.02 kg; p = 0.917). Litter size did not differ between litters with and without cryptorchid piglets in either genetic line. In conclusion, the lower average birth weight in cryptorchid litters of the HPS line, but not in conventional lines, suggests that HPS breeds may influence cryptorchidism incidence. These findings highlight the need to optimize fetal growth especially in the HPS to reduce this risk. Full article

Testicular stiffness is a potential indicator of spermatogenic activity. Herein, we investigated the relationship between testicular stiffness and intratesticular morphology in Syrian hamsters by using a robotic system with a micro-force sensor. Animals were divided into control, sham-operated, and surgically induced cryptorchidism groups. Testicular stiffness, testis weight and size, and Johnsen score data for sham and crypt groups were partially derived from our previous study and reanalysed. Testicular stiffness and histological parameters were analysed, including tunica albuginea thickness, seminiferous tubule occupancy, tubule diameter, intratubular cell-layer thickness, peritubular lamina propria thickness, and Leydig cell numbers. Compared with those of sham and normal controls, cryptorchid testes showed significantly lower stiffness and marked morphological changes, such as reduced tubule occupancy and diameter, thinner intratubular cell layers, thickened tunica albuginea and peritubular lamina propria, and increased numbers of Leydig cells. Decreased testicular stiffness and the Johnsen score, a standard index of spermatogenic function, were strongly related to these structural changes. These findings indicate that structural changes in the testes caused by impaired spermatogenesis are related to measurable differences in tissue stiffness. This study supports using mechanical properties as non-invasive quantitative indices to evaluate testicular function in animal models, offering a novel approach for future research in experimental andrology. Full article