Scrotal Testes Research Articles

Testicular expression of heat SHOCK proteins 60, 70, and 90 in cryptorchid horses

Heat shock proteins are the most evolutionarily conserved protein families induced by stressors including hyperthermia. In the context of pathologies of the male reproductive tract, cryptorchidism is the most common genital defect that compromises the reproductive potential of the male because it induces an increase in intratesticular temperature. In equine species, cryptorchidism affects almost 9 % of newborns and few studies have been carried out on the molecular aspects of the retained testis. In this study, the expression pattern of HSP60, 70, and 90 in abdominal and inguinal testes, in their contralateral descended normally testes, and in testes of normal horses were investigated by Western blot and immunohistochemistry. The histomorphological investigation of retained and scrotal testes was also investigated. The seminiferous epithelium of the retained testes showed a vacuolized appearance and displayed a completely blocked spermatogenesis for lacking meiotic and spermiogenetic cells. On the contrary, the contralateral scrotal testes did not show morphological damage and the seminiferous epithelium displayed all phases of the spermatogenetic cycle as in the normal testes. The morphology of Leydig cells was not affected by the cryptorchid state. Western blot and immunohistochemistry evidenced that equine testis (both scrotal and retained) expresses the three investigated HSPs. More in detail, the Western blot evidenced that HSP70 is the more expressed chaperone and that together with HSP90 it is highly expressed in the retained gonad (P < 0.05). The immunohistochemistry revealed the presence of the three HSPs in the spermatogonia of normal and cryptorchid testes. Spermatogonia of retained testes showed the lowest expression of HSP60 and the highest expression of HSP90. Spermatocytes, spermatids of scrotal testes, and the Sertoli cells of retained and scrotal testes did not display HSP60 whereas expressed HSP70 and HSP90. These two proteins were also localized in the nucleus of the premeiotic cells. The Leydig cells displayed the three HSPs with the higher immunostaining of HSP70 and 90 in the cryptorchid testes. The results indicate that the heat stress condition occurring in the cryptorchid testis influences the expression of HSPs.

MicroRNA as epigenetic regulators of canine cryptorchidism

Cryptorchidism, the failed descent of one or both testes into the scrotum, is a common developmental disorder in male dogs. Cryptorchidism may affect canine fertility, reducing the quality of the semen, and may promote spermatic cord torsion and onset of neoplasia. MicroRNAs (miRNAs) are epigenetic regulators of gene expression and their dysregulation is associated with disorders of spermatogenesis and testis neoplasia. The present study aimed at investigating the expression of miRNAs in formalin-fixed, paraffin-embedded (FFPE) canine retained testes and testes affected by seminoma, and at integrating miRNAs to their target genes. Forty testicular FFPE specimens from 30 dogs were included - 10 scrotal and 10 contralateral retained from 10 unilateral cryptorchid dogs; 10 tumoral testes affected by seminoma from non-cryptorchid dogs; 10 scrotal normal testes from non-cryptorchid dogs included as the control. The expression level of three miRNAs, namely miR-302c-3p, miR-302a-3p, and miR-371-3p, associated with testicular disorders, were quantified using RT-qPCR.The comparative analysis demonstrated that the level of miR-302a-3p and miR-371a-3p were quantifiable exclusively in control testes. The expression level of miR-302c-3p was higher in the control than in the other groups; its expression decreased in retained testes compared to scrotal testes and testes with seminoma. Gene Ontology analysis pointed out that these miRNAs may be involved in the modulation of estrogen and thyroid hormone signaling pathways.In conclusion, this study demonstrated that miRNAs are dysregulated in canine cryptorchid and seminoma-affected testes compared to control tissues, confirming the pivotal role of miRNAs in cryptorchidism.

Microdissection testicular sperm extraction outcomes in azoospermic patients with bilateral orchidopexy.

Cryptorchidism is considered to be one of the most common causes of non-obstructive azoospermia. There are several surgical techniques to retrieve sperm in these patients. Microdissection testicular sperm extraction (m-TESE) is a recent sperm retrieval technique which is considered to be a safe, non-blind, and feasible method. This study aimed to investigate sperm retrieval rate (SRR) by the mTESE method in patients who have undergone orchidopexy due to bilateral cryptorchidism. In this retrospective study, 56 ex-cryptorchid patients, who underwent mTESE due to post orchidopexy azoospermia, were included. Patients with hypogonadotropic hypogonadism, Klinefelter syndrome, azoospermia factors (AZF) microdeletion, or chromosomal translocation were excluded from the study. Data were obtained from medical files. SRR in this study was 46%. Patients were divided into two groups of negative (n=30) and positive (n=26) based on the sperm extraction outcomes. There was no statistically significant difference between two groups regarding the mean age at mTESE, mean age at orchidopexy, testicular size, and serum testosterone concentration. However, testicular location, histological patterns, FSH, and LH level showed to have statistically significant relation with sperm retrieval results. But, according to our logistic regression, none of the included variable in the model including FSH, LH, histopathology, and testis location have a significant effect on the presence of the sperm. In the present study, SRR was significantly higher in patients with scrotal testis and low level of FSH and LH. Performing mTESE could be recommended in ex-cryptorchid patients with post orchidopexy NOA. Preoperative testicular biopsy seems to be unnecessary while clinical criteria can perfectly define NOA.

Effects of therapeutic ultrasound and moderate heat on stallion testes

Transplantation of stem cells into dysfunctional testes is currently being investigated as a therapeutic option for men and stallions with advanced testicular degeneration. This series of “proof of concept” studies aimed to identify a safe and efficient method of inducing severe testicular degeneration to create an optimal equine recipient model for intratesticular stem cell transplantation (SCT). Two ex vivo and two in vivo experiments were conducted. At first, forty testes obtained from castrations were used to identify an effective therapeutic ultrasound (TUS) device and the protocol for increasing intratesticular temperature in stallions. Six min of treatment using the Vetrison Clinic Portable TUS machine raised the intratesticular temperature by 8°C-12.5 °C. This protocol was applied to treat three scrotal testes in three Miniature horse stallions, three times, every other day. Contralateral testes served as controls. There were signs of slight tubular degeneration in treated testes two and three weeks after TUS treatment. The number of seminiferous tubules (STs) with exfoliated germ cells (GCs) was increased in one testis only, three weeks after treatment. The degree of apoptosis of GCs was higher in each treated testis in comparison to the contralateral control testis. Next, the ability of various heating devices to increase intratesticular temperatures to at least 43 °C in stallion testes was tested, using twenty testes obtained from castrations. ThermaCare® Lower Back & Hip Pain Therapy Heatwrap (TC heat wrap) reliably increased intratesticular temperatures and kept them continuously between 43 °C and 48 °C for seven to 8 h. In the follow-up in vivo study, the left testes of three Miniature horse stallions were treated with TUS, after which both testes of each stallion were treated with moderate heat provided by the TC heat wrap (three times, every other day, for 5 h each time). There were signs of moderate tubular degeneration in the samples from all treated testes obtained three weeks after treatments (Heat only or Heat/TUS): areas with hypospermatogenesis, spermatogenic arrest, vacuolized Sertoli cells, numerous STs with exfoliated GCs, increased degree of GCs apoptosis, and changes in three histomorphometric numeric attributes of STs. We concluded that TUS or TC wraps increase intratesticular temperature of the isolated stallion testes. Further, treatment with TUS or moderate heat may induce mild to moderate degenerative changes in stallion testes. However, to achieve more robust result – severe testicular degeneration, our treatment protocol has to be modified.

Correlation Beetwen Body Weight with Scrotal Circumference, Testis Weight and Sperm Production of Boer Buck Intensively Rearing

Body weight of one of the regulators that determine the scrotum circumference and weight (large) testicles. Next, the weight of the testes has a very close relationship with sperm production that will determine the reproductive ability of a male. The purpose of this study was to determine the relationship between body weight and scrotum circumference, testicular weight and boer goat sperm production that was maintained intensively. The study was conducted with a descriptive method with the material of 15 male goats owned by PT. Sadhana Arif Nusa. Data is processed by regression and correlation analysis using the SPSS program. The results showed that the body weight average was 52.58 ± 14.96 kg, correlated very significantly (p &lt;0.01) with scrotum circumference (25.68 ± 1.96 cm) and testicular weight (0.46 ± 0, 10 kg) with a correlation coefficient of 0.67 and 0.91. Body weight not correlated (p&gt; 0.05) with good sperm production volume (0.50 ± 0.19 ml), pH (6.43 ± 0.19), sperm consistency, progressive motility (73.33 ± 7, 24 %) and Spermatozoa concentration (2.18 ± 0.54 x 109/ml). The scrotum circumference is very significantly correlated (p &lt;0.01) with a testicular weight and a real correlation (p &lt;0.05) with sperm volume, motility and concentration of spermatozoa with a coefficient of 0.91 each; 0.58; 0.56 and 0.54. The testes weight is real correlating (p &lt;0.05) with sperm volume, progressive motility and spermatozoa concentration with a coefficient of 0.53 each; 0.56 and 0.54. CONCLUSION, body weight correlates piosif with scrotum circumference, the weight of the quality of the testes and sperm production in boer goats.

Outcome of redo orchidopexy after previous laparoscopic orchidopexy

Testicular reascent is a recognised complication of orchidopexy, and redo surgery may be required. In this report, we present our experience of redo orchidopexy after initial laparoscopic surgery. Patients who had undergone redo orchidopexy following an initial vessel-sparing (VS) or non-vessel sparing (NVS) laparoscopic orchidopexy between 2005 and 2019 were identified. Outcome data, including complications and testicular size, were recorded. The series comprised 23 patients (5: initial bilateral surgery with reascent on one side only; 18: unilateral surgery) with a mean age at original surgery of 3.5years (range 8months-6years) and at redo surgery, 4years (range 1.5-7years). VS surgery had been undertaken in 15 and NVS in 8. A tension-free scrotal position was achieved in all cases. There were no complications and no patient required orchidectomy. At a minimum of 6-month follow-up after redo surgery, there were no cases of reascent and there was no change in testicular size/volume (based on clinical examination). Redo orchidopexy is an effective treatment following failed laparoscopic orchidopexy and a scrotal testis can be achieved in all cases. Complete testicular atrophy did not occur, but the risk of partial atrophy could not be accurately quantified.

Utility of genetic work-up for 46, XY patients with severe hypospadias

Hypospadias is a common congenital abnormality that has been increasing in prevalence over the last decades. Historically, 46, XY patients with severe hypospadias and descended scrotal testes at birth have frequently lacked a genetic diagnosis. Platforms for molecular genetic testing have become more readily available and can offer an insight into underlying genetic causes of severe hypospadias. The goal of this study was to define the anatomical characteristics of severe hypospadias that can accurately define patients with 46, XY severe hypospadias and determine the practical utility of performing molecular genetic testing in this group of patients. Patients who met the criteria for 46, XY severe hypospadias were offered a molecular genetic work-up in consultation with pediatric genetics. Patients were identified through chart review. Data extracted included karyotype, hypospadias phenotype including stretched penile length at diagnosis, age at genetic diagnosis, molecular genetic testing, pathogenic gene variant(s), gender identity, and clinical course. All patients underwent clinical genetic testing via 46, XY Disorders of Sexual Development (DSD) panels offered by Invitae®, GeneDx®, or Blueprint Genetics®. Of the 14 patients that underwent genetic testing, there were 5 previously published and 3 novel pathogenic or likely pathogenic variants in genes associated with 46, XY severe hypospadias (Table). Pathogenic variants were identified in AR (3), SRD5A2 [1], NR5A1 [2], WT1 [1], and ARTX [1]. Two patients had a variant of unknown significance, one in FREM2 and another in CEP41. Four had negative gene panels. The patient with the WT1 pathogenic variant was subsequently found to have developed a Wilms tumor and the patients with NR5A1 pathogenic variants are now undergoing adrenal insufficiency surveillance. Patients with 46,XY severe hypospadias and descended testes in the scrotum at birth can benefit from molecular genetic testing as their underlying disorders may reveal pathogenic variants that could have potentially life-altering consequences and change surveillance and monitoring.

Sperm Dysfunction in the Testes and Epididymides due to Overweight and Obesity Is Not Caused by Oxidative Stress.

Obesity is a condition that has been linked to male infertility. The current hypothesis regarding the cause of infertility is that sperm are highly sensitive to reactive oxygen species (ROS) during spermatogenesis in the testes and transit through the epididymides, so the increase in ROS brought on by obesity could cause oxidative stress. The aim of this study was to evaluate whether the activity of the enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) is capable of counteracting oxidative stress in sperm. The male Wistar rat was used as an overweight and obesity model, and analysis of fertility in these groups was carried out including the control group. Serum testosterone levels were determined, and the scrotal fat, testes, and epididymides were extracted. The epididymides were separated ini0 3 principal parts (caput, corpus, and cauda) before evaluating sperm viability, sperm morphology, damage to desoxyribonucleic acid of the sperm, and ROS production. The protein content and specific activity of the three enzymes mentioned above were evaluated. Results showed a gain in body weight and scrotal fat in the overweight and obese groups with decreased parameters for serum testosterone levels and sperm viability and morphology. Fertility was not greatly affected and no DNA integrity damage was found, although ROS in the epididymal sperm increased markedly and Raman spectroscopy showed a disulfide bridge collapse associated with DNA. The specific activities of CAT and GPX increased in the overweight and obesity groups, but those of SOD did not change. The amounts of proteins in the testes and epididymides decreased. These findings confirm that overweight and obesity decrease concentrations of free testosterone and seem to decrease protein content, causing poor sperm quality. Implications. An increase in scrotal fat in these conditions fosters an increase of ROS, but the increase of GPX and CAT activity seems to avoid oxidative stress increase in the sperm without damaging your DNA.

External Male Genitalia in Henoch-Schönlein Syndrome: A Systematic Review.

The external genitalia are notoriously implicated in every fifth male with Henoch–Schönlein syndrome. Nonetheless, the underlying conditions are poorly categorized. To characterize the involvement of the external male genitalia in this vasculitis, we performed a systematic review of the literature. For the final analysis, we selected 85 reports published between 1972 and 2022, which reported on 114 Henoch–Schönlein cases (≤ 18 years, N = 104) with a penile (N = 18), a scrotal (N = 77), or both a penile and a scrotal (N = 19) involvement. The genital involvement mostly appeared concurrently with or after the cutaneous features of Henoch–Schönlein syndrome, while it preceded the presentation of Henoch–Schönlein syndrome in 10 cases. Patients with penile involvement (N = 37) presented with swelling (N = 26), erythema (N = 23), and purpuric rash (N = 15). Most patients were otherwise asymptomatic except for transient micturition disorders (N = 2) or priapism (N = 2). Patients with scrotal involvement (N = 96) presented with pain (N = 85), swelling (N = 79), erythema (N = 42), or scrotal purpura (N = 22). The following scrotal structures were often involved: scrotal skin (N = 83), epididymis (N = 49), and testes (N = 39). An ischemic testicular damage was noted in nine patients (four with torsion and five without). The scrotal skin involvement was mostly bilateral, while that of the epididymis and testis were mostly (p < 0.0001) unilateral (with a significant predilection for the left side). In conclusion, this analysis allows for better categorization of the involvement of external male genitalia in Henoch–Schönlein vasculitis. Scrotal involvement can result from skin inflammation, epididymitis, orchitis, or testicular ischemia.

Testicular torsions in veterinary medicine

The purpose of this review is to provide a comprehensive comparison of spermatic cord torsion in domestic animals. Spermatic cord torsion leads to occlusion of testicular blood flow resulting in ischemia and tissue hypoxia. Spermatic cord torsion has been reported in all domestic mammals but dogs and horses are overrepresented. Abdominal pain (colic), anorexia, vomiting, lameness, and stiff gait are the most common clinical signs reported. The condition may be asymptomatic in cases of a low degree of spermatic cord torsion. In dogs, spermatic cord torsion is most commonly reported in undescended testes, which in some cases are neoplastic. However, in horses, spermatic cord torsion occurs more commonly in scrotal testes. Surgical treatment for spermatic cord torsion depends upon the degree and duration of torsion. If the affected testis is located within the scrotum and determined to still be viable, detorsion with orchidopexy can be performed. Orchiopexy of the unaffected scrotal testis is also recommended in stallions. If the affected testis cannot be salvaged, unilateral or bilateral orchidectomy is recommended. In all cases of spermatic cord torsion of an undescended testis, orchidectomy is recommended. Veterinarians should be aware of the clinical signs and treatment options for spermatic cord torsion in domestic mammals.

An unusual case of quadruple polyorchidism in a human cadaver mimicking bilateral lipoma

Polyorchidism is a rare congenital disorder defined as the presence of more than two testicles for which the underlying etiology is unknown. This report examines a novel case, correlates findings to the literature, and discusses potential mechanisms of dysgenesis. This study was conducted on a 96-year-old male cadaver. Meticulous skilled dissection was done with careful attention to the pelvis, the inguinal region, the scrotum and testes. Measurements of the scrotal testes (STs), supernumerary testes (SNTs), scrotal epididymides (SEs), supernumerary epididymides (SNEs), ductus deferens (DD) and supernumerary ductus deferens (SDD) were taken, and testicular volume was calculated. Sagittal sectioning of STs, SNTs, SEs and SNEs was performed and, using standard histologic protocol, tissues were processed, stained with H&amp;E, and examined. Histological findings supported the anatomical suspicion of high, bilateral inguinal polyorchdism, or tetraorchdism, in this patient. STs and SNTs have normal, gross morphological features. The left SNT was supplied by the testicular artery, and the right SNT by the inferior epigastric artery. Both SNTs and SNEs were infiltrated with adipose tissue, whereas the scrotal homologues were histologically normal. Testicular volumes were 26.5 cm3 and 23.7 cm3, and 12.3 cm3 and 0.55 cm3, for the left and right STs and SNTs, respectively. The left and right SEs measured 7.2 cm and 7.0 cm; the left and right SNEs measured 4.7 cm and 1.7 cm, respectively. The left DD measured 40.2 cm from the scrotum. The SDD from the left SNT measured 5.9 cm and joined the main ductus 16 cm proximal to its origin. The right main DD measured 39.2 cm, and the SDD from the right SNT was 3.2 cm and joined the main DD 17.4 cm proximal to its origin. The current work suggests a novel classification for polyorchidism of Type 3, Subgroup B, or SNT attached to the draining epididymis and vas deferens without reproductive potential and SNT located outside the scrotal sac. Clinicians must correlate anatomical and histological findings in suspected polyorchids to avoid misdiagnosis of SNTs as benign lipomas.

Comparative genomics reveals molecular mechanisms underlying health and reproduction in cryptorchid mammals

BackgroundMammals have wide variations in testicular position, with scrotal testes in some species and ascrotal testes in others. Although cryptorchidism is hazardous to human health, some mammalian taxa are natural cryptorchids. However, the evolution of testicular position and the molecular mechanisms underlying the maintenance of health, including reproductive health, in ascrotal mammals are not clear.ResultsIn the present study, comparative genomics and evolutionary analyses revealed that genes associated with the extracellular matrix and muscle, contributing to the development of the gubernaculum, were involved in the evolution of testicular position in mammals. Moreover, genes related to testicular position were significantly associated with spermatogenesis and sperm fertility. These genes showed rapid evolution and the signature of positive selection, with specific substitutions in ascrotal mammals. Genes associated with testicular position were significantly enriched in functions and pathways related to cancer, DNA repair, DNA replication, and autophagy.ConclusionsOur results revealed that alterations in gubernaculum development contributed to the evolution of testicular position in mammals and provided the first support for two hypotheses for variation in testicular position in mammals, the “cooling hypothesis”, which proposes that the scrotum provides a cool environment for acutely heat-sensitive sperm and the “training hypothesis”, which proposes that the scrotum develops the sperm by exposing them to an exterior environment. Further, we identified cancer resistance and DNA repair as potential protective mechanisms in natural cryptorchids. These findings provide general insights into cryptorchidism and have implications for health and infertility both in humans and domestic mammals.

Immunohistochemical insights into a hidden pathology: Canine cryptorchidism

Cryptorchidism is a common disorder in the canine population with some aspects still unclear. Although the bilateral condition is known to lead to fertility problems and predisposition to testicular cancer, the neoplastic risk for scrotal testis in unilateral cryptorchid dog is controversial. Therefore, the therapeutic approach to the canine unilateral cryptorchid is arbitrary so far.This study aimed to investigate precancerous testicular lesions, such as immaturity and atrophy, and compare them in scrotal and undescended testes using an in-depth diagnostic analysis based on immunophenotypic patterns. With this purpose, 26 adult male dogs of different ages and breeds, affected by unilateral or bilateral cryptorchidism were enrolled. After surgical removal, testes were examined immunohistochemically to assess their positivity for specific markers of the canine foetal/neonatal period, that is vimentin (VIM), cytokeratin (CK), desmin (DES), inhibin-α (INH), and anti-Müllerian hormone (AMH) in Sertoli cells, and placental alkaline phosphatase (PLAP) in germ cells. Except for the ubiquitous VIM, all the markers were more expressed in neoplastic gonads compared to healthy ones (P < 0.05). Similarly, testes detected with Sertoli cell-only tubules as well as with Sertoli cells hyperplasia showed higher expression than gonads without such alterations for CK, DES, AMH and PLAP, and for CK and DES, respectively (P < 0.05). The same trend was observed in undescended respect to scrotal testes even though their positivity was significant only for DES, INH and AMH (P < 0.05). Immunohistochemical positivity found in scrotal testes of unilateral cryptorchid dogs, even in absence of detectable anatomical abnormalities, was suggestive of precancerous lesions.Despite the limited sample size, this study could help to clarify the predisposition to neoplastic development in normally descended testes. These markers expression in adult life could allow identifying the early stages of the testicular carcinogenesis process besides suggesting a precautionary bilateral surgical approach in unilateral cryptorchid dogs.

The ameliorative effect of curcumin on cryptorchid and non-cryptorchid testes in induced unilateral cryptorchidism in albino rat: histological evaluation.

Cryptorchidism, one or both hidden testes, is the most common abnormality of male sexual development. Subfertility or infertility is associated with both unilateral and bilateral cryptorchidism. In this study, we investigate the possible ameliorative effect of curcumin (Cur) on the induced-unilateral cryptorchidism testicular injury in both cryptorchid (Cryp) and non-cryptorchid (non-Cryp) scrotal testes through histological, immunohistochemical and morphometrics. Forty adult male albino rats were divided into: control group, Cur control group, Cryp group, and Cryp+Cur group. The rat model was surgically established by fixing the left testis in the abdomen. The treated groups were subjected to surgically induced-unilateral cryptorchidism on the left side then were given Cur (80 mg/kg) orally, for 20 days. Histological analysis using haematoxylin and eosin and periodic acid Schiff's reaction was done. Immunohistochemistry was performed for proliferating cell nuclear antigen (PCNA); to estimate the proliferation in the germinal epithelium, and vimentin; to evaluate Sertoli cells. The results were confirmed by statistical evaluation of the spermatogenic epithelium height, the seminiferous tubules diameter, the basement membrane thickness, the number of PCNA immunostained cells and the area per cent of vimentin immunostaining. Distorted seminiferous tubules, substantial degeneration of the germinal epithelium, thickening of the basement membrane with a significant decrease in PCNA and vimentin immunostaining were observed in Cryp group; mainly in the cryptorchid testis. These structural changes were significantly reversed in Crypt+Cur group. Curcumin proved to be an important and effective medical line for protecting against the unfavourable sequels of cryptorchidism in a rat model.

Case Report: Rare Presentation of Mixed Germ Cell Tumor in an Infant

The estimated incidence of pediatric testis tumor is 0.5–2.0 per 100,000 children, accounting for 1–2% of all pediatric tumors. Mixed germ cell tumors (MGCT) in prepubertal males are exceedingly rare, with only one previous case report found in the literature. We report a case of a MGCT in an infant. For prepubertal males, GCTs typically present with a painless scrotal mass, though trauma, testis torsion and hydrocele are also common presentations. Similar to such tumors in postpubertal males, ultrasonography, computed tomography, and tumor markers are integral to determine the best treatment. The patient described in this report presented with a painless scrotal mass. Following orchiectomy, the patient was found to have MGCT that was limited to the testis. With prudent management, these patients tend to have favorable prognoses.

Rapid evolution and molecular convergence in cryptorchidism-related genes associated with inherently undescended testes in mammals

BackgroundThe mammalian testis is an important male exocrine gland and spermatozoa-producing organ that usually lies in extra-abdominal scrotums to provide a cooler environment for spermatogenesis and sperm storage. Testicles sometimes fail to descend, leading to cryptorchidism. However, certain groups of mammals possess inherently ascrotal testes (i.e. testes that do not descend completely or at all) that have the same physiological functions as completely descended scrotal testes. Although several anatomical and hormonal factors involved in testicular descent have been studied, there is still a paucity of comprehensive research on the genetic mechanisms underlying the evolution of testicular descent in mammals and how mammals with ascrotal testes maintain their reproductive health.ResultsWe performed integrative phenotypic and comparative genomic analyses of 380 cryptorchidism-related genes and found that the mammalian ascrotal testes trait is derived from an ancestral scrotal state. Rapidly evolving genes in ascrotal mammals were enriched in the Hedgehog pathway—which regulates Leydig cell differentiation and testosterone secretion—and muscle development. Moreover, some cryptorchidism-related genes in ascrotal mammals had undergone positive selection and contained specific mutations and indels. Genes harboring convergent/parallel amino acid substitutions between ascrotal mammals were enriched in GTPase functions.ConclusionsOur results suggest that the scrotal testis is an ancestral state in mammals, and the ascrotal phenotype was derived multiple times in independent lineages. In addition, the adaptive evolution of genes involved in testicular descent and the development of the gubernaculum contributed to the evolution of ascrotal testes. Accurate DNA replication, the proper segregation of genetic material, and appropriate autophagy are the potential mechanisms for maintaining physiological normality during spermatogenesis in ascrotal mammals. Furthermore, the molecular convergence of GTPases is probably a mechanism in the ascrotal testes of different mammals. This study provides novel insights into the evolution of the testis and scrotum in mammals and contributes to a better understanding of the pathogenesis of cryptorchidism in humans.

Malignancy in an Undescended Intra-abdominal Testis: a Single Institution Experience.

Cryptorchidism is one of the most common congenital anomalies of the genitourinary tract, encountered in 1% of men. The cancer risk in an ectopic testis is 40 times higher than a scrotal testis. However, not much literature is available on the management of this rare presentation of testicular cancer. A retrospective analysis was conducted at our institute of patients who were diagnosed with carcinoma in an undescended intra-abdominal testis between 2014 and 2019. Patients with an intra-abdominal mass with an empty hemiscrotum/scrotum were included in the study. In all 10 patients were identified with a mean age of 32years. Four patients were non-seminomatous germ cell tumors, and other 6 were seminomatous tumors. Five were in stage I, two in stage II, and three in stage III. Six patients received induction chemotherapy with bleomycin, etoposide, and cisplatin, and four had complete response. Five patients underwent laparoscopic excision, and five underwent open surgery. Two patients with bilateral (B/L) cryptorchidism underwent contralateral orchidopexy. Two patients with B/L intra-abdominal gonads and uterus underwent excision of the malignant testicular mass with removal of atrophic uterus and contralateral dysgenetic gonad. One patient developed peritoneal recurrence within 3months of completion of surgery. Both recurrence-free and overall survival were 90% after a median follow-up of 35months. Malignancy in an undescended intra-abdominal testis is a rare presentation of testicular cancer, diagnosis of which requires a sharp correlation between clinical and radiological findings. There management and prognosis remains similar to classical testicular cancer.

Clinical efficacy of two-staged Fowler-Stephens laparoscopic orchidopexy in the treatment of children with high cryptorchidism

Objective: To Evaluate the clinic effect of two-staged laparoscopic Fowler-Stephens orchiopexy in the treatment of high cryptorchidism, and compare it with laparoscopic orchiopexy treatment without disconnecting spermatic vessels. Methods: A retrospective analysis was conducted on 20 cases of children with high cryptorchidism who were treated with two-staged Fowler-Stephens orchiopexy from January 2015 to April 2019 (F-S group). All the children in this group had unilateral cryptorchidism, age 6 to 18 months. The average age was 13.5 months. Seven cases were on the left side, and 13 cases were on the right side. There were 20 control children in the same age group who were treated with testicular fixation without disconnecting spermatic vessels, age 6 to 18 months. The average age was 12.5 months. Six cases were on the left side, and 14 cases were on the right side. Testicular ultrasonography and sex hormone examination were conducted before operation. F-S group met the indications for Fowler-Stephens surgical. In the first stage, the testicular vessels were doubly clipped at a site away from the testis in laparoscopic, and the second stage was scheduled about 6 months after the first stage. The children in the control group were treated with laparoscopic orchiopexy without disconnect spermatic vessels. The two groups were followed up to 6 months after the operation, and the testicular volume and sex hormone indexes of the two groups were measured. The testicular volume and sex hormones before and after the operation of the F-S group and the control group were respectively subjected to a self-control study, and a hormone comparison study was carried out between the two groups of children. Results: Both the F-S group and the control group successfully fixed the testes in the scrotum without tension during the operation. In both groups, 20 cases of testicular positions were reexamined 6 months after the operation without retraction. All the patients had a viable testis in scrotum after operation. Two of F-S group had an atrophic testis in the scrotum, and the others had a good vascularization detected on echo color doppler ultrasound. The average testicular volume of F-S group was (0.34±0.16) ml before operation and the postoperative one was (0.38±0.13) ml, P=0.089, P>0.05. In control group, the preoperative average testicular volume was (0.40±0.14) ml, and postoperative one was (0.40±0.15) ml, P=0.933, P>0.05. The testicular volume of two group had no significant difference. Sex hormone reexamination: Testosterone (T), estradiol (E2) and luteinizing hormone (LH) did not change after operation. Prolactin (PRL) in F-S group was 13.44 μg/L before operation and 12.3 μg/L after operation, PRL in control group was from 15.45 μg/L to 10.34 μg/L, P=0.732, the change of prolactin (PRL) has no significant difference. The median preoperative follicle stimulating hormone (FSH) in the F-S group was 1.18 U/L preoperatively and 1.61 U/L postoperatively; the median FSH of the control group was 1.21 U/L preoperatively and 1.1 U/L postoperatively. Compared between the two groups, the postoperative increase in the FS group was higher than that before the operation, P=0.032, P<0.05, the difference was statistically significant. The median of progesterone (PROG) in the F-S group was 0.25 nmol/L before operation and 0.17 nmol/L after operation; the median PROG of the control group was 0.56 nmol/L before operation and 0.24 nmol/L after operation. It was lower after the operation than before the operation, P=0.034, P<0.05, the difference was statistically significant. Conclusions: (1) Laparoscopic Fowler-stephens staging operation is an effective method for the treatment of patients with high cryptorchidism, and it is worthy of further promotion. (2) Disruption of spermatic cord vessels does have an impact on hormones changes. The choice of this surgical procedure should be carefully and fully evaluated.

Testicular hypertrophy as predictor of contralateral nonpalpable testis among Chinese boys: An 18-year retrospective study

ObjectiveTo assess the accuracy of contralateral testis hypertrophy for predicting the fate of nonpalpable testis in Chinese boys at different ages. MethodsThe data of patients who presented with unilateral impalpable testis and who underwent laparoscopy at the Children's Hospital of Chongqing Medical University between January 1, 2000 and January 1, 2018 were reviewed. The boys were divided into four groups: age-matched volunteers with no testicular abnormalities represented the control group (group I), boys with palpable undescended testis (group II), boys with nonpalpable testis (NPT)/viable testis (VT) (group III), and boys with NPT/non-viable testis (NVT) group (group IV). Scrotal testes were prospectively measured by ultrasonography for volume and size, and diagnostic laparoscopy was performed to determine the state of the cryptorchid testis. ResultsThe mean contralateral testicular volume and length in the boys with an absent testis was 0.78mL and 17mm compared with 0.67mL and 15mm in the boys with a testis present and 0.63mL and 15mm in the controls, respectively (P<0.05). The predictive accuracy, sensitivity, and specificity for an absent testis were 64.9%, 75%, and 49%, respectively, for volume and 64.2%, 56.3%, and 76.4%, respectively for length at the optimal cutoff value of 0.65mL volume and 16.55mm length. Contralateral testis volume was the most accurate in predicting monorchism in 0–2-year-olds (sensitivity: 75%, specificity: 70%, accuracy: 73.1%) and the contralateral testicular length was most accurate for 4–6-years-old (sensitivity: 68.6%; specificity: 77.8%; accuracy: 72.2%). We also included 29 patients with bilateral undescended testis (UDT) and with unilateral nonpalpable. Cutoff values for testicular volume and length were 0.6mL (sensitivity: 81.8%, specificity: 88.9%, accuracy: 86.2%) and 13.5mm (sensitivity: 63.6%, specificity: 77.8%, accuracy: 77.8%). ConclusionThe present results exclusively obtained from laparoscopic exploration suggest that a testis volume of>0.65mL or a testis length of>16.55mm could predict monarchism with an accuracy of about 65%. In younger patients aged 0–2 years and 4–6 years, the overall predictive accuracy increases to about 73% but laparoscopic exploration is still required.

A rare case of discontinuous type splenogonadal fusion in a 13 year old boy: a case report and review of literature

Splenogonadal fusion (SGF) is a rare developmental anomaly in which an abnormal connection between the splenic tissue and gonads or mesonephric derivatives is present. This entity often presents with scrotal mass, inguinal hernia, or cryptorchidism. Less than 200 cases have been reported since it was first described in 1883. It can be of continuous and discontinuous type based on the presence of a band of connecting splenic tissue. Report a rare case of discontinuous type of SGF in an adolescent male presenting as nonpalpable testis. On evaluation, ultrasonography (USG) and magnetic resonance imaging of abdomen and pelvis, his left scrotal testis was atrophied and right intra-abdominal undescended testis. This is the first reported case of SGF from Bosnia and Herzegovina. Laparoscopy was demonstrated to be the only accurate exploratory procedure for the diagnosis and surgical treatment of SGF with non‑palpable testis.