ABSTRACT
Testicular tumors are rarely reported in rabbits. In this case study, a 4-year-old Holland lop rabbit, previously diagnosed with unilateral cryptorchidism, was presented because of enlargement of the descended testis. The rabbit was clinically normal. Following unilateral orchiectomy and scrotal ablation, histopathological analysis revealed 2 distinct types of testicular tumor in the descended testis: a granular cell tumor and a seminoma. To the best of the author's knowledge, this is the first documented report of simultaneous testicular tumors in the testis of a rabbit with unilateral cryptorchidism.
Tumeur à cellules granulaires et séminome simultanés dans le testicule descendu d'un lapin cryptorchideLes tumeurs testiculaires sont rarement rapportées chez le lapin. Dans cette étude de cas, un lapin Holland Lop de 4 ans, précédemment diagnostiqué avec une cryptorchidie unilatérale, a été présenté en raison d'une hypertrophie du testicule descendu. Le lapin était cliniquement normal. Après orchidectomie unilatérale et ablation scrotale, l'analyse histopathologique a révélé 2 types distincts de tumeur testiculaire dans le testicule descendu : une tumeur à cellules granuleuses et un séminome. À la connaissance de l'auteur, il s'agit du premier rapport documenté de tumeurs testiculaires simultanées dans le testicule d'un lapin atteint de cryptorchidie unilatérale.(Traduit par Dr Serge Messier).
Subject(s)
Cryptorchidism , Granular Cell Tumor , Orchiectomy , Seminoma , Testicular Neoplasms , Animals , Male , Rabbits , Testicular Neoplasms/veterinary , Testicular Neoplasms/pathology , Testicular Neoplasms/surgery , Cryptorchidism/veterinary , Cryptorchidism/surgery , Cryptorchidism/pathology , Seminoma/veterinary , Seminoma/pathology , Seminoma/surgery , Granular Cell Tumor/veterinary , Granular Cell Tumor/pathology , Granular Cell Tumor/surgery , Orchiectomy/veterinaryABSTRACT
BACKGROUND: Congenital inguinal hernia, hydrocele and undescended testis (UDT) are associated with patent processus vaginalis. The smooth muscles present in the processus vaginalis aid in the descent of the testis and undergo programmed cell death after testicular descent leading to obliteration. The persisting amount of smooth muscle in the processus vaginalis influences the clinical outcome as inguinal hernia, hydrocele or UDT. Therefore, a study was conducted to evaluate the processus vaginalis in these three conditions to observe the presence and phenotype of smooth muscle cells and the presence of myofibroblasts. MATERIALS AND METHODS: The processus vaginalis sacs in patients with inguinal hernia, hydrocele and UDT were examined using light microscopy for the presence and distribution of smooth muscle cells and immunohistochemical staining for vimentin, desmin, and α-smooth muscle actin (SMA) to identify the smooth muscle phenotype. Transmission electron microscopy was also performed in all the sacs to observe the presence of myofibroblasts. RESULTS: Seventy-eight specimens of processus vaginalis (from seventy-four patients), distributed as 47%, 27%, and 26% as inguinal hernia, hydrocele and UDT respectively, were included in the study. The sacs from inguinal hernia and hydrocele had significantly more presence of smooth muscles distributed as multiple smooth muscle bundles (p < 0.001). Desmin and SMA staining of smooth muscle cells was observed in significantly more sacs from hydrocele, followed by inguinal hernia and UDT (p < 0.001). The sacs from UDT had a significant presence of striated muscles (p = 0.028). The sacs from inguinal hernia had a significant presence of myofibroblasts, followed by hydrocele and UDT (p < 0.001) and this significantly correlated with the light microscopy and immunohistochemical features. The processus vaginalis sacs from four female patients did not differ statistically from the male inguinal hernia sacs in any of the above parameters. CONCLUSION: The processus vaginalis sacs in pediatric inguinal hernia, hydrocele and undescended testis differ in the presence, distribution and phenotype of smooth muscles and the presence of myofibroblasts. The clinical presentations in these entities reflect these differences.
Subject(s)
Cryptorchidism , Hernia, Inguinal , Myocytes, Smooth Muscle , Myofibroblasts , Testicular Hydrocele , Humans , Male , Testicular Hydrocele/pathology , Hernia, Inguinal/pathology , Infant , Cryptorchidism/pathology , Child, Preschool , Myocytes, Smooth Muscle/pathology , Child , Myofibroblasts/pathology , Infant, NewbornABSTRACT
Myxosarcoma is a rare malignant mesenchymal neoplasm of soft tissues originating from fibroblasts. This report describes a case of bilateral myxosarcoma in a three-year-old cryptorchid dog. The animal was referred to the veterinary clinic because of the absence of testicles in the scrotum. Ultrasonography revealed two masses in the abdominal cavity with testicular echotexture. Exploratory laparotomy revealed the presence of cryptorchid testicles, and orchiectomy was recommended to treat the animal. Testicles were gray and reddish in color and enlarged with firm consistency. For histopathological analysis, testis fragments were fixed in 10% formalin and stained with hematoxylin and eosin and Alcian blue. Immunohistochemistry was performed using the following primary antibodies:1A4, HHF35, desmin, glial fibrillary acidic protein, CD31, S-100, vimentin, and Ki-67. Histopathological evaluation revealed the proliferation of fusiform and round cells associated with extensive areas of myxoid matrix. Neoplasms featured multinucleated giant cells, pleomorphism, karyomegaly, nuclear hyperchromasia, anisokaryosis, mitoses, and necrosis, with coarse chromatin and prominent nucleoli. Immunohistochemical analysis of vimentin- and the Alcian blue-positive cells confirmed the diagnosis of myxosarcoma. A high mitotic count and Ki-67 proliferative index suggests this myxosarcoma had a high degree of malignancy. To the best of our knowledge, this is the first case report of bilateral testicular myxosarcoma in a cryptorchid animal.
Subject(s)
Cryptorchidism , Dog Diseases , Myxosarcoma , Testicular Neoplasms , Male , Animals , Dogs , Dog Diseases/pathology , Dog Diseases/surgery , Testicular Neoplasms/veterinary , Testicular Neoplasms/pathology , Testicular Neoplasms/surgery , Myxosarcoma/veterinary , Myxosarcoma/pathology , Cryptorchidism/veterinary , Cryptorchidism/pathology , Orchiectomy/veterinary , Immunohistochemistry/veterinaryABSTRACT
Cryptorchidism, the failure of one or both testes to descend into the scrotum, and testicular cancer show a strong correlation in both dogs and humans. Yet, long-standing medical debates persist about whether the location of undescended testes directly causes testicular cancer in humans or if both conditions stem from a common origin. Although testicular cancer is a prevalent disease in dogs, even less is known about its cause and correlation with testicular descent in this species. This review investigates the relation between these two disorders in dogs, drawing insights from human studies, and examines key biomarkers identified thus far. In addition, it explores potential causal links, including the impact of temperature on maturing testicular cells and a potential shared genetic origin. Notably, this literature review reveals significant differences between men and dogs in reproductive development, histological and molecular features of testicular tumors, and the prevalence of specific tumor types, such as Sertoli cell tumors in cryptorchid dogs and germ cell tumors in humans. These disparities caution against using dogs as models for human testicular cancer research and underscore the limitations when drawing comparisons between species. The paper concludes by suggesting specific research initiatives to enhance our understanding of the complex interplay between cryptorchidism and testicular cancer in dogs.
Subject(s)
Cryptorchidism , Dog Diseases , Testicular Neoplasms , Cryptorchidism/veterinary , Cryptorchidism/genetics , Cryptorchidism/pathology , Dogs , Testicular Neoplasms/veterinary , Testicular Neoplasms/genetics , Testicular Neoplasms/pathology , Animals , Humans , Male , Dog Diseases/genetics , Dog Diseases/pathologyABSTRACT
AIM: To assess testicular volume at puberty for boys who underwent orchidopexy at 9 or at 36 months compared to boys with spontaneous postnatal descent. METHODS: At age 6 months, boys with congenital unilateral cryptorchidism were randomised to surgery at 9 or 39 months of age and followed to 16 years in parallel with boys with spontaneous postnatal descent. Ultrasound was done at 11 and 16 years to determine testicular volume. The ratio of the initially undescended testis to its scrotal counterpart was used to assess testicular growth. RESULTS: At age 16, the ratio was lower (p < 0.00) in the late group compared to the early group. At 16 years, the spontaneously descended testes were significantly smaller than their scrotal counterparts but larger than the operated groups (early p < 0.01 and late p < 0.00). CONCLUSION: Our data at 16 years show that orchidopexy at 9 months results in better testicular growth compared to 3 years but did not reach the corresponding volumes of their scrotal counterparts. This indicates that earlier surgery is beneficial to testicular growth. At age 16, the postnatally descended testes were not only larger than the surgically treated testes but also exhibited impaired testicular growth.
Subject(s)
Cryptorchidism , Orchiopexy , Puberty , Testis , Humans , Male , Cryptorchidism/surgery , Cryptorchidism/diagnostic imaging , Cryptorchidism/pathology , Testis/growth & development , Testis/diagnostic imaging , Adolescent , Infant , Child , Child, Preschool , Puberty/physiology , Organ Size , Ultrasonography , Age Factors , Follow-Up StudiesSubject(s)
Cryptorchidism , Germ Cells , Testis , Male , Cryptorchidism/pathology , Cryptorchidism/metabolism , Humans , Testis/pathology , Testis/metabolism , Germ Cells/metabolism , Germ Cells/cytology , AnimalsABSTRACT
This study aims to explore the optimal management strategy for pediatric vanishing testes syndrome (VTS) based on pathological characteristics. We retrospectively analyzed clinical data and pathological results of children with unilateral VTS who underwent surgical treatment at our center from July 2012 to July 2023. The children were categorized into the testicular excision group and testicular preservation group based on the surgical approach. Clinical characteristics and outcomes were compared between the two groups. Pathological examination results of excised testicular tissues were collected and analyzed, and long-term follow-up was conducted. A total of 368 children were included in this study. The age of the children at the time of surgery was 27 months (range, 6-156). Among them, 267 cases (72.6%) had VTS on the left side, and 101 cases (27.4%) on the right side. There were no statistically significant differences (P > 0.05) in age, affected side, contralateral testicular hypertrophy (CTH), testicular location, and preferred surgical incision between the testicular excision group (n = 336) and the testicular preservation group (n = 32). In the preservation group, two children experienced scrotal incision infections, showing a statistically significant difference compared to the excision group (P < 0.05). Pathological examination of excised tissues revealed fibrosis as the most common finding (79.5%), followed by vas deferens involvement (67%), epididymis involvement (40.5%), calcification (38.4%), and hemosiderin deposition (17.9%). Seminiferous tubules (SNT) was present in 24 cases (7.1%), germ cells (GC)in 15 cases (4.5%), and ectopic adrenal cortical tissue(EACT) in 1 case (0.3%). VTS belongs to a type of non-palpable testes (NPT) and requires surgical exploration. Considering the risk of scrotal incision infection after preserving atrophic testicular remnants and the unpredictable malignant potential, we recommend excision.
Subject(s)
Testis , Humans , Male , Retrospective Studies , Child, Preschool , Child , Testis/surgery , Testis/pathology , Infant , Adolescent , Cryptorchidism/surgery , Cryptorchidism/diagnosis , Cryptorchidism/pathologyABSTRACT
PURPOSE: To identify the genetic cause of a cryptorchidism patient carrying a non-canonical splicing variant highlighted by SPCards platform in RXFP2 and to provide a comprehensive overview of RXFP2 variants with cryptorchidism correlation. METHODS: We identified a homozygous non-canonical splicing variant by whole-exome sequencing and Sanger sequencing in a case with cryptorchidism and non-obstructive azoospermia (NOA). As the pathogenicity of this non-canonical splicing variant remained unclear, we initially utilized the SPCards platform to predict its pathogenicity. Subsequently, we employed a minigene splicing assay to further evaluate the influence of the identified splicing variant. Microdissection testicular sperm extraction (micro-TESE) combined with intracytoplasmic sperm injection (ICSI) was performed. PubMed and Human Genome Variant Database (HGMD) were queried to search for RXFP2 variants. RESULTS: We identified a homozygous non-canonical splicing variant (NM_130806: c.1376-12A > G) in RXFP2, and confirmed this variant caused aberrant splicing of exons 15 and 16 of the RXFP2 gene: 11 bases were added in front of exon 16, leading to an abnormal transcript initiation and a frameshift. Fortunately, the patient successfully obtained his biological offspring through micro-TESE combined with ICSI. Four cryptorchidism-associated variants in RXFP2 from 90 patients with cryptorchidism were identified through a literature search in PubMed and HGMD, with different inheritance patterns. CONCLUSION: This is the first cryptorchidism case carrying a novel causative non-canonical splicing RXFP2 variant. The combined approach of micro-TESE and ICSI contributed to an optimal pregnancy outcome. Our literature review demonstrated that RXFP2 variants caused cryptorchidism in a recessive inheritance pattern, rather than a dominant pattern.
Subject(s)
Cryptorchidism , Pregnancy Outcome , Receptors, G-Protein-Coupled , Sperm Injections, Intracytoplasmic , Humans , Cryptorchidism/genetics , Cryptorchidism/pathology , Male , Sperm Injections, Intracytoplasmic/methods , Pregnancy , Female , Receptors, G-Protein-Coupled/genetics , Pregnancy Outcome/genetics , Adult , Azoospermia/genetics , Azoospermia/pathology , Sperm Retrieval , Exome Sequencing , RNA Splicing/geneticsABSTRACT
Cryptorchidism is the condition in which one or both testes have not descended adequately into the scrotum. The congenital form of cryptorchidism is one of the most prevalent urogenital anomalies in male newborns. In the acquired form of cryptorchidism, the testis that was previously descended normally is no longer located in the scrotum. Cryptorchidism is associated with an increased risk of infertility and testicular germ cell tumors. However, data on pubertal progression are less well-established because of the limited number of studies. Here, we aim to review the currently available data on pubertal development in boys with a history of non-syndromic cryptorchidism-both congenital and acquired cryptorchidism. The review is focused on the timing of puberty, physical changes, testicular growth, and endocrine development during puberty. The available evidence demonstrated that the timing of the onset of puberty in boys with a history of congenital cryptorchidism does not differ from that of non-cryptorchid boys. Hypothalamic-pituitary-gonadal hormone measurements showed an impaired function or fewer Sertoli cells and/or germ cells among boys with a history of cryptorchidism, particularly with a history of bilateral cryptorchidism treated with orchiopexy. Leydig cell function is generally not affected in boys with a history of cryptorchidism. Data on pubertal development among boys with acquired cryptorchidism are lacking; therefore, more research is needed to investigate pubertal progression among such boys.
Subject(s)
Cryptorchidism , Testicular Neoplasms , Infant, Newborn , Humans , Male , Cryptorchidism/pathology , Testicular Neoplasms/pathology , Leydig Cells/pathology , Puberty/physiologySubject(s)
Angiolipoma , Cryptorchidism , Testicular Neoplasms , Testis , Humans , Male , Cryptorchidism/diagnosis , Cryptorchidism/pathology , Cryptorchidism/surgery , Testicular Neoplasms/pathology , Testicular Neoplasms/diagnosis , Testicular Neoplasms/surgery , Testicular Neoplasms/diagnostic imaging , Testis/pathology , Testis/diagnostic imaging , Angiolipoma/pathology , Angiolipoma/diagnosis , Angiolipoma/surgeryABSTRACT
BACKGROUND: 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. OBJECTIVES: This study aimed to investigate sperm retrieval rate (SRR) by the mTESE method in patients who have undergone orchidopexy due to bilateral cryptorchidism. MATERIALS AND METHODS: 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. RESULTS: 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. DISCUSSION: In the present study, SRR was significantly higher in patients with scrotal testis and low level of FSH and LH. CONCLUSIONS: 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.
Subject(s)
Azoospermia , Cryptorchidism , Klinefelter Syndrome , Humans , Male , Orchiopexy , Retrospective Studies , Microdissection/methods , Semen , Testis/surgery , Testis/pathology , Spermatozoa/pathology , Cryptorchidism/surgery , Cryptorchidism/pathology , Sperm Retrieval , Follicle Stimulating HormoneABSTRACT
Introduction: The fertility of cryptorchidism patients who didn't perform corrective surgery will decrease with age. Herein, we elucidate the histological alterations and underlying molecular mechanism in patients with an increase in the disease duration from 20 to 40 years. Methods: Testicular tissues were obtained from three patients with cryptorchidism, ranging in age from 22 to 44 years. Three benign paracancerous testicular samples of matched ages were used as controls. The normal and undescended testicular tissues were stained with hematoxylin and eosin (HE) and immunofluorescence and all six testicular samples were subjected to RNA sequencing. RNA sequencing data were subjected to gene set enrichment analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) network analysis, and Gene Ontology (GO) searches. Real-time reverse transcriptase polymerase chain reaction was used to confirm the DEGs. Results: The seminiferous tubules' basement membrane thickens with age in healthy testes. As the period of cryptorchidism in the cryptorchid testis extended, the seminiferous tubules significantly atrophy, the number of spermatogenic cells declines, and the amount of interstitial fibrous tissue increases in comparison to normal tissues. The number of germ cells per cross-section of seminiferous tubules was significantly lower in cryptorchidism than in normal testicular tissues, according to immunofluorescence staining, but the number of Sertoli cells remained stable. RNA sequencing analysis identified 1150 differentially expressed genes (DEGs) between cryptorchidism and normal testicular tissues (fold change >2 and p<0.05), of which 61 genes were noticeably upregulated and 1089 were significantly downregulated. These genes were predominantly linked to sperm development and differentiation, and fertilization, according to GO analysis. Meiosis pathways were significantly downregulated in cryptorchidism, according to KEGG pathway analysis and GSEA (P<0.001). PPI analysis was used to identify the top seven downregulated hub genes (PLCZ1, AKAP4, IZUMO1, SPAG6, CAPZA3, and ROPN1L), which were then further verified by qPCR. Discussion: By describing the histological changes and differential gene expression patterns in adult cryptorchid patients of different age groups, we discovered the progression mechanisms of undescended testes in adults with aging and identified seven significantly downregulated hub genes (PLCZ1, AKAP4, IZUMO1, SPAG6, CAPZA3, and ROPN1L) in cryptorchid testis compared to normal testicular tissues. These genes played a role in the process of spermgenesis and are directly linked to the steady decline in fertility caused by cryptorchidism. Our study provided a better understanding of the molecular mechanisms underlying the loss of spermatogenesis in adult cryptorchidism, and give support for the development of adult cryptorchidism treatments.
Subject(s)
Cryptorchidism , Humans , Adult , Male , Young Adult , Cryptorchidism/genetics , Cryptorchidism/pathology , Semen , Spermatogenesis/genetics , Sequence Analysis, RNAABSTRACT
OBJECTIVES: Persistent Mullerian duct syndrome (PMDS) is a rare disorder of sexual differentiation resulting from aberrations in the Mullerian inhibiting factor (MIF) pathway, with consequent failure of regression of fetal Mullerian duct. The concomitant association of undescended testis increases the likelihood of developing testicular tumors in these patients. Due to its rarity, clinic-pathologic and treatment outcome data on testicular cancer in PMDS is sparse. We present our institutional experience and review published literature on testicular cancer in PMDS. MATERIAL AND METHODS: We retrospectively queried our institutional testicular cancer database for all patients with a diagnosis of testicular cancer and PMDS, between January 1980 and January 2022. Additionally, a Medline/PubMed search was performed for English language articles published during the same time period. Data on pertinent clinical, radiologic, and pathologic disease characteristics were abstracted, in addition to treatment received and outcomes. RESULTS: Of 637 patients treated for testicular tumors during the specified time period in our institution, 4 patients had a concomitant diagnosis of PMDS. Testicular tumor was pathologically confirmed as seminoma in 3, 1 had mixed germ cell tumor. All patients in our series presented with stage 2B or higher disease and required chemotherapy, either in the neoadjuvant or adjuvant setting, in addition to surgery. With a mean follow up of 67 months, all patients were disease free. Medline/PubMed search retrieved 44 articles (49 patients) of testicular tumors associated with PMDS, with majority (59%) presenting with a large abdominal mass. Only 5 cases (10%) had a preceding history of appropriately managed cryptorchidism. CONCLUSIONS: Testicular cancer in PMDS usually presents in adults with advanced stage disease resulting from neglected or inadequate management of cryptorchidism. Appropriate management of cryptorchidism in childhood is likely to decrease malignant degeneration, if not, enable early-stage diagnosis.
Subject(s)
Cryptorchidism , Testicular Neoplasms , Male , Adult , Humans , Testicular Neoplasms/complications , Testicular Neoplasms/therapy , Testicular Neoplasms/diagnosis , Cryptorchidism/complications , Cryptorchidism/surgery , Cryptorchidism/pathology , Retrospective StudiesABSTRACT
The descent of the testis and the development of an inguinal hernia were the earliest published scientific work by John Hunter, the Scottish surgeon and anatomist who is acknowledged as the father of scientific surgery. Hunter's anatomic descriptions are the ones we use today to describe the prenatal descent of the testis and to explain the pathogenesis of an undescended testis and inguinal hernia in infancy. His work appeared in print in 1762, not as a formal publication but as an addendum to a screed written by his older brother William publicly accusing Percival Pott of pirating John's observations on the pathogenesis of an inguinal hernia and publishing them as his own, an early example of scientific rivalry.
Subject(s)
Cryptorchidism , Hernia, Inguinal , Male , Humans , Testis/pathology , Hernia, Inguinal/surgery , Hernia, Inguinal/pathology , Cryptorchidism/surgery , Cryptorchidism/pathologyABSTRACT
PURPOSE: 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. METHODS: 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. RESULTS: 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 3.5 years (range 8 months-6 years) and at redo surgery, 4 years (range 1.5-7 years). 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). CONCLUSION: 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.
Subject(s)
Cryptorchidism , Laparoscopy , Male , Humans , Infant , Orchiopexy , Cryptorchidism/surgery , Cryptorchidism/pathology , Testis/surgery , Testis/pathology , Treatment Outcome , Atrophy , Retrospective StudiesABSTRACT
INTRODUCTION/BACKGROUND: Currently the standard treatment for bilateral cryptorchidism is bilateral surgical orchidopexy. Whether a hormonal treatment should be routinely administered postoperatively to increase fertility is debatable. Low-dose postoperative luteinizing hormone releasing hormone (LHRH) can increase spermatogonial numbers, but the effect of native LHRH (Kryptocur®) on adult fertility is unclear. OBJECTIVE: To determine if low-dose every-second-day postoperative LHRH administration in children with bilateral cryptorchidism improves fertility in adulthood and if Nistal testicular histological grading could guide the decision to administer LHRH. STUDY DESIGN METHODS: All patients, actually at least 16yr of age, that underwent a bilateral orchidolysis and orchidopexy for bilateral cryptorchidism (surgery between 1997 and 2018) were contacted and offered a clinical exam, hormone levels, sperm analysis, and a scrotal ultrasound. At the original surgery, testicular biopsy was performed (if 60% of the tubuli contain >1 spermatogonia, this is normal = Nistal-1, if 30-60% filled = Nistal-2, if <30% = Nistal-3 and if Sertoli only = Nistal-4) and if in at least one testis impaired. A low dose native LHRH treatment was offered to the patients, as this treatment is known to increase the number of spermatogonia in a short term. Kryptocur® (LHRH, Gonadorelin, Hoechst®) was prescribed and dosed at 200 µg (one spray in one nostril) every other day for 6-8 months. RESULTS AND LIMITATIONS: Forty-two men were eligible for this study. 20/42 accepted the invitation for a clinical and hormonal evaluation. 16/20 men accepted the invitation for an additional sperm analysis. Fourteen of 20 men received low-dose LHRH postoperatively in a nonrandomized manner. Three men had Nistal grade 1, eight grade 2, seven grade 3, and two had grade 4. Inhibin B levels were higher in men with Nistal 1 and 2 compared with Nistal 3 and 4 P ≤ 0.037). Severe oligospermia/azoospermia (<1 × 106/ejaculate) was observed in 33% of the treated group vs 67% of the untreated group (P ≤ 0.036.) DISCUSSION AND CONCLUSIONS: Low-dose every-second-day postoperative LHRH treatment improves fertility outcome in bilateral cryptorchidism. Histological analysis of prepubertal testes according to Nistal grading cannot be used as a predictive diagnostic test for LHRH treatment.
Subject(s)
Cryptorchidism , Adult , Humans , Male , Child , Cryptorchidism/drug therapy , Cryptorchidism/surgery , Cryptorchidism/pathology , Orchiopexy/methods , Semen , Testis/surgery , Gonadotropin-Releasing Hormone/pharmacology , Gonadotropin-Releasing Hormone/therapeutic use , FertilityABSTRACT
Cryptorchidism in males constitutes a notable risk factor for both infertility and testicular cancer. Infertility in adulthood is closely linked to the germ cell status in childhood. Furthermore, the significance of germ cell status is important as more than 95% of all reported testicular malignancies are germ cell tumors. The review aims to elucidate the pathogenesis of germ cells in cryptorchid testes concerning their association with infertility and testicular malignancies. Impaired germ cell numbers are evident in cryptorchid testes even during antenatal and neonatal stages. In cryptorchidism there is a rapid decline in germ cell number within the first year of life, partially attributed to physiologic gonocyte apoptosis. Additionally, germ cells fail to differentiate normally during mini-puberty leading to reduced germ cell proliferation and delayed clearance of gonocytes from the seminiferous epithelium. Absence of germ cells in testicular biopsies occurs already 10 months of age and germ cell deterioration progressively worsens with approximately 50% of persisting cryptorchid testes lacking germ cells during puberty. The deficient germ cell maturation and proliferation leads to later infertility. Elevated temperature in the cryptorchid testes and also hormonal deficiency contribute to this phenomenon. Germ cell neoplasia in situ (GCNIS) originating during fetal development may manifest in rare cases associated with disorders of sexual development, chromosomal abnormalities in boys, specific syndromes, and teratomas that include cryptorchidism. In adults, the presence of GCNIS predominantly represents a new histology pattern before invasive germ cell cancer is demonstrated and is neither congenital nor related to abnormal gonocyte transformation.
Subject(s)
Cryptorchidism , Germ Cells , Humans , Male , Cryptorchidism/pathology , Germ Cells/pathology , Infertility , Testicular Neoplasms/pathologyABSTRACT
The hypoxic microenvironment of cryptorchidism is an important factor in the impairment and fibrosis of Sertoli cells which result in blood-testis barrier (BTB) destruction and spermatogenesis loss. Recent studies have shown that melatonin, a well-known pineal hormone exerts beneficial effects against pathological fibrosis in a various of organs. However, it is still unknown whether melatonin can regulate hypoxia-induced fibrosis of Sertoli cells. In this study we evaluate melatonin levels, and its synthesizing enzymes, AANAT and HIOMT expression patterns in canine cryptorchidism and contralateral normal testis. Results show abdominal testes presented low melatonin levels and AANAT and HIOMT expression compared with testes located in the scrotum. Moreover, we established a hypoxia-induced fibrosis model in canine Sertoli cells induced by cobalt chloride (CoCl2) and found that melatonin inhibited the EMT markers expression and ECM production as well as Hif-1α expression of Sertoli cells in a dose-dependent manner. Furthermore, use of Lificiguat (synonyms YC-1, Hif-1α inhibitor) to interfere with the Hif-1α pathway showed a similar effect with melatonin suppression of the fibrosis in Sertoli cells. The results indicate that melatonin supplementation can alleviate the fibrosis process of Sertoli cells caused by hypoxia, which is associated with regulating the inhibition of Hif-1α signaling.
Subject(s)
Cryptorchidism , Melatonin , Animals , Dogs , Male , Acetylserotonin O-Methyltransferase , Cryptorchidism/pathology , Cryptorchidism/veterinary , Fibrosis , Hypoxia/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors , Melatonin/pharmacology , Sertoli Cells/metabolismABSTRACT
BACKGROUND: There is limited information about the prevalence and risk factors of inguinal hernia and undescended testis in patients with spina bifida (SB). The aim of this study was to identify the properties and prevalence of inguinoscrotal diseases in these patients. METHODS: A questionnaire was completed by parents of patients with the diagnosis of SB in our center. Together with demographic data, presence an of inguinal hernia, side, operation history, presence of ventriculoperitoneal (VP) shunt, type of SB aperta or occulta, recurrence and presence of undescended testis were questioned. Patients were grouped into 2 as SB aperta and occulta. The prevalence of these pathologies and their clinical properties were evaluated. RESULTS: In this study, 388 patients were evaluated. Of these, 238 patients had SB aperta and 150, SB occulta. There was no significance in comparison of gender. The prevalence of inguinal hernia was 12.6% in general. A hernia was noted in 37 SB aperta patients (15.6%) whereas this was seen in 12 of the SB occulta patients (8%) (p=0.029). When there was a VP shunt, hernia prevalence was 21.5% and when there was no shunt, this ratio was 7.1% (p=0.0001). Prevalence of inguinal hernia was 21.8% in males and 3.2% in females (p=0.0001). When there was a VP shunt with SB aperta the prevalence was 21.9% and when a VP shunt was present with SB occulta, this number was found to be 13.3% (p=0.006). The prevalence of undescended testis was 17.7% and there was no difference between SB aperta and occulta patients. CONCLUSIONS: Inguinal hernia and undescended testis are more frequent in SB patients when compared to the normal population. VP shunts and male gender may be risk factors for inguinal hernia in these children. These findings may imply neurological factors in the etiology of inguinal hernia and undescended testis.