Adult Cryptorchid Research Articles

Laparoscopic orchidopexy for the treatment of cryptorchidism in adults: a description of the technique and outcomes

BackgroundThere are few studies on cryptorchidism in adults, and its treatment is still controversial.MethodsTo summarize the surgical strategy and clinical efficacy of laparoscopic orchidopexy for the treatment of cryptorchidism in adults, 37 adult cryptorchidism patients were retrospectively analyzed between September 2017 and February 2022. All 37 patients underwent laparoscopic orchidopexy, of whom 33 underwent inguinal hernia repair without tension. The intraoperative procedures and surgical techniques were recorded in detail. Preoperative examination and regular postoperative review of color Doppler ultrasound, and reproductive hormone, alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase levels were performed.ResultsAll testes descended successfully into the scrotum, including 25 through the inguinal route and 12 through Hesselbach’s triangle route. No intraoperative or postoperative complications were observed. The follow-up time was 38.6 (± 19.4) months, and no evidence of testicular malignancy was found during the follow-up period. After analyzing the reproductive hormone levels at 1 year postoperatively in 28 patients with more than 1 year of follow-up, it was found that the patients had a significant increase in testosterone levels and a decrease in follicle-stimulating hormone levels after surgery. None of the patients showed any significant improvement in semen quality after surgery.ConclusionOur study suggests that laparoscopic orchidopexy is a safe and feasible surgical procedure for the treatment of cryptorchidism in adults, especially high cryptorchidism, which is difficult to treat. After comprehensive consideration, preserving the testis should be preferred for treating cryptorchidism in adults to maximize the protection of the patient’s reproductive hormone secretion function.

RNA sequencing profiles reveals progressively reduced spermatogenesis with progression in adult cryptorchidism.

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. 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. 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. 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.

Clinical Characteristics and Treatment of Cryptorchidism in Adults : Our Experience in Alsaidi Hospital in Aden, Yemen

Clinical Characteristics and Treatment of Cryptorchidism in Adults : Our Experience in Alsaidi Hospital in Aden, Yemen

PD25-12 FERTILITY POTENTIAL OF MEN TREATED FOR UNCORRECTED BILATERAL CRYPTORCHIDISM AS ADULTS: A SYSTEMATIC LITERATURE REVIEW

You have accessJournal of UrologyInfertility: Epidemiology & Evaluation II (PD25)1 Apr 2020PD25-12 FERTILITY POTENTIAL OF MEN TREATED FOR UNCORRECTED BILATERAL CRYPTORCHIDISM AS ADULTS: A SYSTEMATIC LITERATURE REVIEW Wade Muncey*, Rahul Dutta, Ryan P. Terlecki, Lynn L. Woo, and Kyle Scarberry Wade Muncey*Wade Muncey* More articles by this author , Rahul DuttaRahul Dutta More articles by this author , Ryan P. TerleckiRyan P. Terlecki More articles by this author , Lynn L. WooLynn L. Woo More articles by this author , and Kyle ScarberryKyle Scarberry More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000882.012AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bilateral undescended testicles (bUDT) is typically recognized early in life, but may go unaddressed into adulthood. Guidelines on post-pubertal management are lacking, and the hormonal and fertility benefits of adult orchidopexy (OP) are not well established. We aim to conduct a literature review to determine an evidence-based approach to management. METHODS: A systematic literature review, conforming to the PRISMA statement, was conducted using the PubMed/Medline databases through October 2019 using the search terms “adult cryptorchidism” and “adult orchidopexy.” Any report or series including an adult (age>17) with untreated, bilateral undescended testicles was included. RESULTS: 51 reports were identified with 209 adults with uncorrected bUDT included for analysis. Semen analysis (SA) identified azoospermia in 100% (139/139). Unilateral (23%) or bilateral (77%) OP was performed in 132 men. Intraabdominal testicles were identified in 40 patients (30%), one or both inguinal testicles in 38 (29%), or unspecified location in 54 (41%). SA after OP was reported in 43 men (age 18-38) in 14 series with 11 cases (25.6%) identifying return of sperm to ejaculate. Five reports described delayed testicular sperm extraction (TESE) in 18 men with persistent azoospermia at a median of 8 (6-168) months after OP with success in 8 (44%). Only 1 report exists of sperm obtained after OP for intraabdominal testicles. The remainder had OP for inguinal testicles (13) or unspecified location (5). Successful paternity was reported in six men: natural conception (2), intrauterine insemination (1), intracytoplasmic sperm injection (ICSI) with ejaculated sperm (1), and TESE + ICSI (2). TESE was performed in 12 men at time of OP with 0% sperm retrieval. One man had successful TESE 84 months after failed TESE during OP. Pathology of 55 UDTs in 40 men following pre-OP biopsy (64%) or contralateral orchiectomy (36%) revealed no cases (0%) of mature spermatozoa identification and complete lack of germ cells in 51%. Median testosterone in 67 men was 360 ng/dl (90-700), with hypogonadism identified in 9 (13%), but normal puberty reported in all. One report noted de novo hypogonadism post-OP. CONCLUSIONS: Azoospermia is the rule in adults with uncorrected bUDT, but testosterone is sufficient for pubertal development. Adult orchidopexy can restore spermatogenesis, with retrieval noted from ejaculate or TESE. TESE of the uncorrected UDT is of limited benefit and should be abandoned and reserved for after OP. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e543-e543 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wade Muncey* More articles by this author Rahul Dutta More articles by this author Ryan P. Terlecki More articles by this author Lynn L. Woo More articles by this author Kyle Scarberry More articles by this author Expand All Advertisement PDF downloadLoading ...

Chances of Sperm Retrieval during Testicular Sperm Extraction in Adult Cryptorchid Testes

Chances of Sperm Retrieval during Testicular Sperm Extraction in Adult Cryptorchid Testes

Male Infertility as a Circumstance of Discovery of Adult Cryptorchidism: A Retrospective Analysis from the Region of Thies

Introduction: The aim of this work is to study the clinical aspects and the impact of cryptorchidism on male infertility in the region of Thies. Patients and methods: This is a retrospective study involving 28 patients followed up at the Saint Jean de Dieu, Barthimée and Tivaouane hospitals of the region of Thies between January 2007 and December 2016. Results: Among the 223 patients followed up for the undescended testicle, 13% (n = 28) were adults or at least 15 years old. 71% (n = 20) were married. Fourteen patients were followed up for primary infertility lasting for a period of time averaging 7 years. The mean age of the patients was 28 years (range: 17 years and 45 years). Cryptorchidism was unilateral in 82% (n = 23) and bilateral in 18% (n = 5). The mean delay of consultation varied from 1 to 13 years. The main reason for consultation was couple infertility (50%). The semen analysis was requested in all our patients. The levels of FSH, LH and testosterone were measured by immunoassay for the patients with azoospermia (n = 9). We noticed 2 cases of hypotestosteronemia and 3 cases of increased FSH serum level. Computed Tomography scans (CT) were performed in 28.5% of patients (n = 8) and ectopic testicles were found very high in the inguinal area in 5 cases. The open inguinal approach was used. In perioperative period, the testicle was found, high in the inguinal region in 5 patients (17.8% of the cases) and low in inguinal region in 19 patients (67.8%). In 4 cases the testicle was in abdominal position. The testicle was atrophied in 53.5% of the patients (n = 15) and 8 patients presented testicular hypotrophy. An orchidectomy was performed in 1 patient in whom it was impossible to lower the atrophied testicle. The postoperative period was uneventful and simple. The mean follow-up duration after the operation was 36 months (12 - 60 months).

88 - Consequences of bilateral cryptorchidism in adults

Summary Bilateral cryptorchidism treatment results are often shadowed by the majority of unilateral cases. We report the long-term follow-up results of boys treated for bilateral cryptorchidism during childhood. Patients treated in two main paediatric surgery centres were selected from medical registries and invited for a clinical examination including scrotal ultrasound, salivary testosterone measurement and a semen sample. Thirty-six men (38.3%) replied to the written invitation, and 21 agreed to be examined. The mean age at orchidopexy was 74 months (range 24–138). Sperm count was 0.42 × 106 (SD ± 0.64 × 106) ml−1. The correlation between total testicular volume and total sperm count was statistically significant (r = 0.481; P = 0.032). These results show that surgical treatment of bilateral cryptorchidism after the age of 2 years does not prevent infertility. Sperm count and endocrine evaluation advocated after the treatment of bilateral cryptorchidism in all adult patients.

Consequences of bilateral cryptorchidism in adults.

Bilateral cryptorchidism treatment results are often shadowed by the majority of unilateral cases. We report the long-term follow-up results of boys treated for bilateral cryptorchidism during childhood. Patients treated in two main paediatric surgery centres were selected from medical registries and invited for a clinical examination including scrotal ultrasound, salivary testosterone measurement and a semen sample. Thirty-six men (38.3%) replied to the written invitation, and 21 agreed to be examined. The mean age at orchidopexywas 74months (range 24-138). Sperm count was 0.42×106 (SD±0.64×106 )ml-1 . The correlation between total testicular volume and total sperm count was statistically significant (r=0.481; P=0.032). These results show that surgical treatment of bilateral cryptorchidism after the age of 2years does not prevent infertility. Sperm count and endocrine evaluation advocated after the treatment of bilateral cryptorchidism in all adult patients.

Clinical Characteristics and Treatment of Cryptorchidism in Adults: A Single Center Experience

PurposeWe evaluated the clinical and therapeutic characteristics of adult cryptorchidism, which have been difficult to establish, given the small number of patients presenting to outpatient clinics.Materials and MethodsA retrospective study of 20 adult patients with cryptorchid testis was performed. We analyzed their palpation of testis, location, surgical method, marital status, number of children, histologic findings, and semen analysis.ResultsIn 17 cases with unilateral cryptorchidism, the mean age at surgery was 31.1±12.5 years. Fourteen patients had a palpable, small cryptorchid testis. The location of the testis, as verified, was inguinal in 14, prepubic in 2, and intra-abdominal in 1, respectively. We performed orchiopexy in 14 out of 15 patients who sought to have this procedure. Four among 6 married patients had children. Testis biopsy was performed in 12 patients, and all showed abnormal histologic findings. Three among 4 patients, performed semen analysis, showed abnormal findings. In three cases of bilateral cryptorchidism, the mean age at surgery was 35.7±12.5 years. All of these patients had palpated cryptorchid testes in the inguinal area and sought to have a bilateral orchiopexy. Two patients have been married but had no children. All showed abnormal findings in both testis biopsy and semen analysis. No testicular neoplasm was detected during the duration of follow-up.ConclusionsMost adult patients with cryptorchidism preferred orchiopexy to orchiectomy. However, most of patients showed abnormal histology of the testis and semen analysis. Therefore, orchiopexy with regular scrotal examination may be considered a suitable treatment options for adult cryptorchidism.

Unilateral Cryptorchidism in Mice Mutant forPtgds

The pathophysiology of cryptorchidism, abnormal testicular descent, remains poorly understood. In this study, we show that both heterozygous and homozygous mice deficient for lipocalin-type prostaglandin D(2) (PGD(2) ) synthase (Ptgds) presented unilateral cryptorchidism affecting the second phase of testicular descent in 16% and 24% of cases, respectively. The adult cryptorchid testes show an increase in spermatogonia apoptosis along with a global decrease in the tubule size parameters, whereas the gubernaculum of newborn mutants present some histological abnormalities. Disruption of the inguinoscrotal phase did not present impairment of the androgen pathway but rather a decrease in Rxfp2 mRNA expression in the gubernaculum. These observations led us to investigate the role of the PGD(2) signaling pathway in human testicular migration through PTGDS sequencing of DNA from 29 children with cryptorchidism. However, none of the investigated cases presented mutations in the PTGDS gene. Nevertheless, our results identify the PTGDS enzyme as a novel component in the cryptorchidism puzzle.

Unresolved abdominal mass in an adult cryptorchid testis: a case report

This case study aims to report an unresolved abdominal mass in an adult with cryptorchid testis and provide a review of related literature. We investigated a 54-year-old man who had cryptorchidism with a history of left orchiectomy 18 years prior. He was diagnosed with an intra-abdominal testicular mass after referring to the emergency ward with pelvic pain. The incidence of testicular cancer in undescended testicles is 40 times greater in the general population. In developed countries, the existence of undescended testicles in adult population is rare, which could be due to systematic practice of elective orchidopexy before the second year of life as well as orchiectomy in post-adolescent patients with undescended testicles. Despite these preventive measures, there are still some isolated cases of intra-abdominal testicular tumors in adults.

V1396 MANAGEMENT OF FERTILITY IN ADULT INTRA-ABDOMINAL CRYPTORCHIDISM

You have accessJournal of UrologyInfertility, Sexual Dysfunction, Trauma & Teaching Techniques1 Apr 2010V1396 MANAGEMENT OF FERTILITY IN ADULT INTRA-ABDOMINAL CRYPTORCHIDISM John Kefer, Kashif Siddiqi, Jihad Kaouk, and Edmund Sabanegh John KeferJohn Kefer More articles by this author , Kashif SiddiqiKashif Siddiqi More articles by this author , Jihad KaoukJihad Kaouk More articles by this author , and Edmund SabaneghEdmund Sabanegh More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1067AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Adult cryptorchidism is a rare problem, but one that offers significant challenges towards management of both infertility and oncological risks. Options towards management include observation, orchidopexy, or orchiectomy with testicular sperm extraction (onco-TESE). This video demonstrates our technique for the management of a rare but significant disease process. METHODS A 22 year old male with a past surgical history of two previously failed attempts at bilateral orchidopexy (Fowler-Stevens). Relevant laboratory analysis included a testosterone of 770, FSH of 29, LH of 17, and semen analysis demonstrating normal volume azoospermia. Testicular tumor markers were also drawn, indicating Alpha fetoprotein (AFP) of 29 (normal <11), Beta human chorionic gonadotropin (BHCG) of 0.1, and lactate dehydrogenase (LDH) of 181. Based on the wishes of the patient and family, and after extensive counseling regarding the risks of testicular malignancy, the decision was made to undergo bilateral laparoscopic orchiectomy with ex vivo onco-TESE if normal testicular tissue was found. RESULTS Based on the location of the left and right testicles on preoperative MRI, we chose to perform bilateral procedures using separate port placements for left and right orchiectomy. Operative time was 95 minutes. Estimated blood loss was minimal. Surgical landmarks included identification of the surgical clips from the previous failed Fowler-Stevens procedures. Both testicles were identified and excised. No normal testicular tissue was identified on ex vivo onco-TESE. No sperm was isolated. A palpable solid mass was noted in the right testicle, and pathology revealed a mixed germ cell tumor. The patient was discharged on post-operative day 2 without complication. CONCLUSIONS Adult cryptorchidism is a rare problem, and requires management of fertility issues and oncologic risks. Treatment algorithms should include cryopreservation of testicular tissue when possible, and aggressive management of oncologic risks, including orchidopexy when possible to assist with testicular screening exams, or orchiectomy when orchidopexy is not possible. Cleveland, OH© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e539 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information John Kefer More articles by this author Kashif Siddiqi More articles by this author Jihad Kaouk More articles by this author Edmund Sabanegh More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Immunodetection of inhibin in the human testis and epididymis during normal development and in non-tumoural testicular lesions

Plasma concentrations of inhibin are correlated with spermatogenetic function. Inhibin is secreted mainly by the Sertoli and Leydig cells of the testis. In the human epididymis, the location and function of inhibin are contentious. Thus, the aim of the present study was to determine the location of inhibin in the human epididymis. Investigations were performed in samples with normal testicular function at different stages of development, as well as in samples in which testicular function or the testicular-epididymal connection were altered. In fetal, newborn and infant testes, Sertoli and Leydig cells stained positive for inhibin, whereas no such staining was detected in the epididymides. Inhibin was located in both the Sertoli and Leydig cells, as well as in the epididymis, in the apical pole of mainly secretory cells in the efferent ducts. This staining pattern was not correlated with the staining pattern for macrophages. The main duct of the epididymis was negative for inhibin staining. In ischaemic atrophic testes, the few tubules in which Sertoli cells were present stained positive for inhibin, whereas the epididymides stained negative. In paediatric cryptorchidism, Sertoli and Leydig cells stained positive for inhibin, whereas the epididymides were negative. In adult cryptorchidism, Sertoli and Leydig cells stained positive for inhibin, even in tubules containing Sertoli cells only. Interestingly, inhibin was absent from the efferent ducts. In three cases undergoing hormonal treatment prior to subsequent gender change, Sertoli and Leydig cells stained positive for inhibin. In contrast, the efferent ducts were negative or only faintly positive in cases of shorter hormonal treatment. In all cases studied, the presence of inhibin in the efferent ducts was associated with its production in the testis, suggesting that the epididymis is not responsible for the production of inhibin in men. The pattern of inhibin staining does not correlate with that of macrophages, suggesting that inhibin is not degraded in the human epididymis. The data suggest that, in humans, inhibin is secreted by Sertoli cells into the seminiferous tubules and then travels towards the efferent ducts, where it is reabsorbed into the bloodstream.

Multi-vacuolated leydig cells in human adult cryptorchid testes.

A histological study of 23 testicular biopsies or surgical specimens from adult cryptorchid testes revealed the presence of multi-vacuolated Leydig cells in 12 cases. These cells showed abundant lipid inclusions and scarce secondary lysosomes as well as liprofuchsin pigment granules. Some of these cells contained crystals of Reinke but others had only microcristalline inclusions. This Leydig cell alteration may be related either to heat or to congenital lesions.

Expression of aromatase and oestrogen receptors in reproductive tissues of the stallion and a single cryptorchid visualised by means of immunohistochemistry

Androgen metabolism may proceed to amplify the action of testosterone by its aromatisation to oestradiol. Recently, a growing body of evidence suggests a role of oestrogens in the male reproductive tract via their specific oestrogen receptors (ERs). In order to check whether androgens are converted to oestrogens in the testis, epididymis and prostate of the stallion, the expression of aromatase was visualised by means of immunohistochemistry. Moreover, to show the cellular targets for oestrogens the presence of oestrogen receptor α (ERα) and oestrogen receptor β (ERβ) was demonstrated in these tissues. Finally, to show whether naturally occurring cryptorchidism has any influence on the localisation of aromatase and distribution of ERs, the reproductive tissues of a single horse, bilaterally cryptorchid, were also taken for this study. The results demonstrated that aromatase and ERs are ubiquitously distributed throughout the male reproductive tract, what indicates a putative role of oestrogens in modulating the function of the reproductive tissues of the stallion. In the cryptorchid horse the increase in conversion of androgen to oestrogen was observed as manifested by aromatase overexpression. This is the first report showing the cellular site of oestrogen biosynthesis not only in the testis but also in the epididymis and prostate of sexually mature stallion and a single, adult cryptorchid.

Laparoscopic Assessment and Treatment of Non-Palpable Testis in an 18-Year-Old Male

Laparoscopy, both diagnostic and therapeutic, has been used in the management of pediatric non-palpable testes. We report a case of left non-palpable testis at the unusual age of 18 years. Laparoscopic exploration revealed an intra-abdominal testis lying between the internal inguinal ring and external iliac vessels. The testis was visually in good condition and, in contrast to the accepted procedure of orchiectomy performed in late adolescent cryptorchidism, we decided to preserve this intra-abdominal testis, which was located too far from the scrotum for a primary orchidopexy. The first stage of the Fowler-Stephens procedure was performed laparoscopically. The second-stage orchidopexy was performed successfully through an inguinal approach 3 months later, after sonographic ascertainment of non-decreased testicular volume. Laparoscopy allows thorough exploration for an intra-abdominal testis, with simultaneous therapeutic options. Our experience highlights the feasibility of laparoscopic assessment and treatment of cryptorchidism in adolescents and young adults.

Disrupted expression of intermediate filaments in the testis of rhesus monkey after experimental cryptorchidism.

Cytoskeletons in Sertoli cell play an important role in process of spermatogenesis. The expression and distribution of the intermediate filaments, vimentin, keratin and desmin, were studied in the Sertoli cells of the cryptorchid testis of rhesus monkey. Vimentin was localized in the perinuclear region of Sertoli cells of the normal testis. An intense increase in vimentin immunoreactivity was observed with appearance of disorganized staining in the Sertoli cells of the cryptorchid testes. Cytokeratin 18, a marker of immature Sertoli cells, re-expressed in the cells of the adult cryptorchid testes. Desmin was also observed in the Sertoli cells in addition to the peritubular myoid cells on 30 days after the cryptorchid operation. These data suggest that Sertoli cells in primate can be affected by the heat stress. The altered changes in intermediate filaments could be possible to induce the Sertoli cell functional changes that would partially contribute to the germ cell apoptosis leading to azoospermia or oligozoospermia.

Focal orchitis in undescended testes: discussion of pathogenetic mechanisms of tubular atrophy.

To evaluate seminiferous epithelium lesions in adult cryptorchid testes showing lymphoid infiltrates in seminiferous tubules and interstitium (i.e., focal orchitis). Also, to consider the possible role of this lesion in the etiology of tubular atrophy. We performed a histopathologic study of the cryptorchid testes and adjacent epididymides removed from 50 adult men who had not been previously treated for cryptorchidism. The study included morphologic and semiquantitative evaluation of seminiferous tubule pathology (according to germ cell numbers), Sertoli cell morphology, tubular lumen dilation, rete testis pattern (normal, hypoplastic, or cystic), and epididymal pattern (normal or epididymal duct hypoplasia). The study also included immunohistochemical evaluation of immune cell markers. The results were compared with clinical and laboratory findings. Focal lymphoid infiltrates (mainly lymphocytes) in seminiferous tubules and interstitium were found in 22 patients (44%), all of whom had unilateral cryptorchidism. The course of orchitis was asymptomatic, and laboratory data were normal. According to the seminiferous tubule pathology, a variety of histopathologic diagnoses, were made: (1) mixed atrophy consisting of Sertoli cell-only tubules intermingled with tubules showing maturation arrest of spermatogonia (11 testes, 4 of which also showed hyalinized tubules); (2) Sertoli cell-only tubules plus hyalinized tubules (4 testes); (3) Sertoli cell-only tubules (3 testes); (4) intratubular germ cell neoplasia (2 testes, 1 of which also showed hyalinized tubules); (5) complete tubular hyalinization (1 testis); and (6) tubular hyalinization plus some groups of tubules with hypospermatogenesis (all germ cell types were present although in lower numbers, 1 testis). Dysgenetic Sertoli cells, that is, Sertoli cells that had undergone anomalous, incomplete maturation, were observed in all nonhyalinized seminiferous tubules with inflammatory infiltrates. Tubular ectasia was observed in 13 cases. The rete testis was hypoplastic and showed cystic transformation in 18 testes, and the epididymis was hypoplastic in 15 testes. The causes of these focal inflammatory infiltrates are unknown. It is possible that tubular ectasia and Sertoli cell dysgenesis are involved and that these alterations cause a disruption of the blood-testis barrier and allow antigens to enter the testicular interstitium, giving rise to an autoimmune process.

Spermatogonial stem cell enrichment by multiparameter selection of mouse testis cells.

The spermatogonial stem cell initiates and maintains spermatogenesis in the testis. To perform this role, the stem cell must self replicate as well as produce daughter cells that can expand and differentiate to form spermatozoa. Despite the central importance of the spermatogonial stem cell to male reproduction, little is known about its morphological or biochemical characteristics. This results, in part, from the fact that spermatogonial stem cells are an extremely rare cell population in the testis, and techniques for their enrichment are just beginning to be established. In this investigation, we used a multiparameter selection strategy, combining the in vivo cryptorchid testis model with in vitro fluorescence-activated cell sorting analysis. Cryptorchid testis cells were fractionated by fluorescence-activated cell sorting analysis based on light-scattering properties and expression of the cell surface molecules alpha6-integrin, alphav-integrin, and the c-kit receptor. Two important observations emerged from these analyses. First, spermatogonial stem cells from the adult cryptorchid testis express little or no c-kit. Second, the most effective enrichment strategy, in this study, selected cells with low side scatter light-scattering properties, positive staining for alpha6-integrin, and negative or low alphav-integrin expression, and resulted in a 166-fold enrichment of spermatogonial stem cells. Identification of these characteristics will allow further purification of these valuable cells and facilitate the investigation of molecular mechanisms governing spermatogonial stem cell self renewal and hierarchical differentiation.

Improvement of spermatogenesis in adult cryptorchid rat testis by intratesticular infusion of lactate.

In order to test the hypothesis that a lack of energy could be a cause of germ cell death at high temperatures, cryptorchid rats testes were infused with lactate, delivered by osmotic pumps over 3-15 days. In cryptorchid testes, the spermatids and spermatocytes were lost between 3 and 8 days. In cryptorchid testes supplemented with lactate, elongated spermatids persisted in a few seminiferous tubules at Day 15. Elimination of round spermatids occurred progressively between 3 and 15 days, mostly at stage VIII. The loss of spermatocytes increased after 8 days, and 30% of seminiferous tubules still contained meiotic or meiotic plus spermiogenetic cells at Day 15. After 8 days, the chromatin of step 8 round spermatids was abnormal and nuclear elongation did not commence. The Sertoli cell cytoplasm that was retracted toward the basal compartment of the seminiferous epithelium could not hold the germ cells of the adluminal compartment. Therefore, attachment of germ cells to Sertoli cells and the supply of lactate seem necessary for the development of germ cells at high temperatures. The improvement in spermatogenesis in cryptorchid supplemented testes for several days is a new finding.