Epididymal disjunction anomalies in undescended testis - a factor associated with spermatic obstruction

ABSTRACT Background: To analyze the incidence of epididymal anomalies (EAs) associated to spermatic obstruction in patients with undescended testis (UT) according to testicular position and age. Materials and Methods: We studied 87 patients (110 testis) with cryptorchidism and analyzed the presence of EAs correlated with the testicular position, age and patency of the processus vaginalis (PV). To analyze the relations between the testis and epididymis we considered three situations: (a) Normal pattern: the epididymis was attached to the testis at the head and tail and epididymis totally attached to the testis; (b) EAs: when the epididymis was attached to the testis only at the head (Figure-1A) and (c) EAs associated to spermatic obstruction: epididymis was attached to the testis only at the tail (Figure-1B) and when there are no visible connection between testis and epididymis (Figure-1C). We used the Wilcoxon-Mann-Whitney test and the Chi-square test for contingency analysis (p <0.05). Results: The mean age of the patients was 5.18 years (SD=2.867). Of 110 testes analyzed, 14 were abdominal (12.72%); 83 inguinal (75.45%) and 13 suprascrotal (11.81%). Normal relationships between testis and epididymis were observed in 54 patients (62.1%) with no significant differences in relation to the patient's age (p=0.666). Epididymal tail disjunction was observed in 23 patients (26.44%), with no significant differences in relation to age (p=0.59). EAs associated to spermatic obstruction were observed in 16 patients (18.4%), also with no significant differences in relation to age (p=0.684). We did not observe significant correlation between the testis position and the incidence of EAs (p=0.119). We did not observe significant correlations between patency of the PV (64.7%) and incidence of EAs (p=0.742). Conclusions: Epididymal anomalies associated with spermatic obstruction are present in almost 20% of undescended testes, without significant correlation with age, testicular position and patency of the PV. This information needs to be correlated to the infertility risk of this congenital anomaly.

Deficiency of the transcription factor PLAG1 results in aberrant coiling and morphology of the epididymis.

Mice deficient in the transcription factor pleomorphic adenoma gene 1 (PLAG1) exhibit reproductive issues that are characterized, in part, by decreased progressive sperm motility in the male. However, the underlying cause of this impairment is unknown. As epididymal transit is critical for sperm maturation and motility, the morphology of the epididymis of Plag1-deficient mice was investigated and the spatial expression patterns of PLAG1 protein and mRNA were identified. Using X-gal staining and in situ hybridization, PLAG1 was shown to be widely expressed in both the epithelium and stroma in all regions of the mouse epididymis. Interestingly, the X-gal staining pattern was markedly different in the cauda, where it could be suggestive of PLAG1 secretion into the epididymal lumen. At all ages investigated, the morphology of epididymides from Plag1 knockout (KO) mice was aberrant; the tubule failed to elongate and coil, particularly in the corpus and cauda, and the cauda was malformed, lacking its usual bulbous shape. Moreover, the epididymides from Plag1 KO mice were significantly reduced in size relative to body weight. In 20% of Plag1-deficient mice, the left testicle and epididymis were lacking. The impaired morphogenesis of the epididymal tubule is likely to be a major contributing factor to the fertility problems observed in male Plag1-deficient mice. These results also establish PLAG1 as an important regulator of male reproduction, not only through its involvement in testicular sperm production, but also via its role in the development and function of the epididymis.

Do retractile testes have anatomical anomalies?

ABSTRACT Objectives: To assess the incidence of anatomical anomalies in patients with retractile testis. Materials and Methods: We studied prospectively 20 patients (28 testes) with truly retractile testis and compared them with 25 human fetuses (50 testes) with testis in scrotal position. We analyzed the relations among the testis, epididymis and patency of the processus vaginalis (PV). To analyze the relations between the testis and epididymis, we used a previous classification according to epididymis attachment to the testis and the presence of epididymis atresia. To analyze the structure of the PV, we considered two situations: obliteration of the PV and patency of the PV. We used the Chi-square test for contingency analysis of the populations under study (p <0.05). Results: The fetuses ranged in age from 26 to 35 weeks post-conception (WPC) and the 20 patients with retractile testis ranged in ages from 1 to 12 years (average of 5.8). Of the 50 fetal testes, we observed complete patency of the PV in 2 cases (4%) and epididymal anomalies (EAs) in 1 testis (2%). Of the 28 retractile testes, we observed patency of the PV in 6 cases (21.4%) and EA in 4 (14.28%). When we compared the incidence of EAs and PV patency we observed a significantly higher prevalence of these anomalies in retractile testes (p=0.0116). Conclusions: Retractile testis is not a normal variant with a significant risk of patent processus vaginalis and epididymal anomalies.

Epididymal anomalies in boys with undescended testis or hydrocele: Significance of testicular location.

BACKGROUND: Epididymal anomalies and patent processus vaginalis are frequently found in boys with cryptorchidism or hydrocele. We conducted this study to evaluate the association between epididymal anomalies and testicular location or patent processus vaginalis in boys with undescended testis or hydrocele. METHODS: Children undergoing surgery with undescended testis (group A, 136 boys and 162 testes) or communicating hydrocele (group B, 93 boys and 96 testes) were included. Testicular locations and epididymal anomalies were investigated prospectively. An anomalous epididymis was defined as anomalies of epididymal fusion that consisted of loss of continuity between the testis, the epididymis, and the long looping epididymis. The epididymis was considered normal when a normal, firm attachment between the testis, the caput, and the cauda epididymis was present. RESULTS: The mean ages of groups A and B were 24.6 ± 19.7 (range, 8-52 months) and 31.4 ± 20.6 months (range, 10-59 months). The incidence of epididymal anomalies was significantly higher in group A than that in group B (65.4 % vs. 13.5 %, P < .001). The incidence of epididymal anomalies in boys with undescended testis was significantly different according to testis location. Epididymal anomalies were observed in 100 %, 91.4 %, and 39.3 % of cases when the testis was located in the abdomen, inguinal canal, and distal to the external inguinal ring, respectively (P < 0.001). CONCLUSION: We conclude that epididymal anomalies were more frequent in boys with undescended testis than in boys with hydrocele, and that these anomalies were more frequent when undescended testis was at a higher level. These results suggest that testicular location is associated with epididymal anomalies rather than patent processus vaginalis.

The Histone Methyltransferase Gene Absent, Small, or Homeotic Discs-1 Like Is Required for Normal Hox Gene Expression and Fertility in Mice.

Chromatin remodeling influences gene expression in developing and adult organisms. Active and repressive marks of histone methylation dictate the embryonic expression boundaries of developmentally regulated genes, including the Hox gene cluster. Drosophila ash1 (absent, small or homeotic discs 1) gene encodes a histone methyltransferase essential for regulation of Hox gene expression that interacts genetically with other members of the trithorax group (TrxG). While mammalian members of the mixed lineage leukemia (Mll) family of TrxG genes have roles in regulation of Hox gene expression, little is known about the expression and function of the mammalian ortholog of the Drosophila ash1 gene, Ash1-like (Ash1l). Here we report the expression of mouse Ash1l gene in specific structures within various organs and provide evidence that reduced Ash1l expression has tissue-specific effects on mammalian development and adult homeostasis. Mutants exhibit partially penetrant postnatal lethality and failure to thrive. Surviving mutants have growth insufficiency, skeletal transformations, and infertility associated with developmental defects in both male and female reproductive organs. Specifically, expression of Hoxa11 and Hoxd10 are altered in the epididymis of Ash1l mutant males and Hoxa10 is reduced in the uterus of Ash1l mutant females. In summary, we show that the histone methyltransferase Ash1l is important for the development and function of several tissues and for proper expression of homeotic genes in mammals.

Bilateral isolated Epididymal Agenesis in a 32 year old man

Epididymal agenesis is defined as the absence of the epididymis totally or segmentally, unilateral or bilateral, which is secondary to the Wolffian duct malformation (1). Rete testis, epididymis, vas deferens and seminal vesicle are believed to develop from Wolffian ducts.

The separation of the epididymis and the abnormal attachment of the gubernaculum cause undescendence in the rat testes.

PURPOSE: Epididymal anomalies are common in cryptorchid patients. This led us to consider that anomalies of the epididymis, to which the gubernaculum is attached, or abnormal attachment of the cranial end of the gubernaculum, could lead to cryptorchidism. METHODS: Twenty-eight male Sprague-Dawley rats were divided into two groups: In Group 1 rats (n = 14), the epididymis was isolated from the testis, and in Group 2 rats (n = 14), the gubernaculum was isolated from the epididymis and re-attached to the tail of the epididymis. In both groups, the non-operated testes were used as the control. RESULTS: In Group 1, cryptorchidism rates were 1/14 in the control testes and 8/14 in the operated testes (p < 0.01). In Group 2, cryptorchidism rates were 0/13 in the control testes and 6/13 in the operated testes (p < 0.01). CONCLUSION: Cryptorchidism was seen when the epididymis was loosely or non-connected to the testis and the gubernaculum was attached solely to the epididymis (mimicking anomalies of ductal fusion) and when the gubernaculum was attached to the tail of the epididymis (mimicking anomalies of ductal suspension). Therefore epididymal anomalies and abnormal attachment of the gubernaculum may play a role in the undescendence of the testes in the rats.

The prevalence of bell clapper anomaly in the solitary testis in cases of prior perinatal torsion.

PURPOSE: Bell clapper anomaly is associated with an increased risk of intravaginal testicular torsion. However, perinatal torsion is thought to be secondary to an extravaginal process. We quantified the contralateral prevalence of bell clapper anomaly in children found to have atrophic testicular nubbins secondary to presumed torsion during gestation to better define the subsequent risk of metachronous testicular torsion. MATERIALS AND METHODS: Inspection results for the presence of contralateral bell clapper anomaly was recorded by a single surgeon in 50 consecutive cases in which exploration for nonpalpable testes revealed a testicular nubbin. For comparison data were collected in 27 consecutive cases of acute testicular torsion. Anatomy of the normal contralateral testis was compared between the 2 groups. RESULTS: Average age at surgery in the perinatal torsion group was 15 months vs 12.7 years in the acute torsion group. One case of partial contralateral bell clapper anomaly was discovered in the perinatal torsion group but no complete anomaly was found. In contrast, in older boys with acute testicular torsion complete bell clapper anomaly was found in 21 of the 27 contralateral testes (78%). CONCLUSIONS: In older boys with acute testicular torsion contralateral bell clapper anomaly is highly prevalent, supporting the standard practice of contralateral testicular fixation in this clinical situation. However, the prevalence of contralateral bell clapper anomaly is exceedingly small in cases of monorchism after perinatal torsion, substantiating an insufficient risk of subsequent torsion to justify routine fixation of the solitary testis.

Triorchidism: two case reports.

In this study, two cases of triorchidism are reported. The first case (29 years) had two right discrete ovoid nontender, firm, mobile lumps with testicular sensation. The second case (32 years) had two left discrete ovoid nontender, firm, mobile lumps with normal testicular sensation. They were subjected to the estimation of serum follicle-stimulating hormone, luteinising hormone, free and total testosterone, alpha-fetoprotein, prostate-specific antigen, karyotyping and semen analysis. Imaging included ultrasonography, transrectal ultrasound, magnetic resonance imaging and intravenous pyelography. The first case had two testes in the right side. Each one had an epididymis where one vas deferens was palpated. The second case had two left testes with normal testicular sensation. The lower left lump represented normal-sized testis attached to its epididymis and a single palpated vas deferens. Diagnosis of the first case was triorchidism associated with left varicocele (grade I) with oligoasthenoteratozoospermic semen profile. Intracytoplasmic sperm injection was carried out resulting in a twin. Diagnosis of the second case was triorchidism with accessory testis on the left side associated with left varicocele (grade I) and asthenozoospermic semen profile that was submitted to medical treatment. It is concluded that triorchidism is an uncommon congenital anomaly that should be not overlooked in diagnosing scrotal masses.

Pkd1 is required for male reproductive tract development.

Reproductive tract abnormalities and male infertility have higher incidence in ADPKD patients than in general populations. In this work, we reveal that Pkd1, whose mutations account for 85% of ADPKD cases, is essential for male reproductive tract development. Disruption of Pkd1 caused multiple organ defects in the murine male reproductive tract. The earliest visible defect in the Pkd1(-/-) reproductive tract was cystic dilation of the efferent ducts, which are derivatives of the mesonephric tubules. Epididymis development was delayed or arrested in the Pkd1(-/-) mice. No sign of epithelial coiling was seen in the null mutants. Disruption of Pkd1 in epithelium alone using the Pax2-cre mice was sufficient to cause efferent duct dilation and coiling defect in the epididymis, suggesting that Pkd1 is critical for epithelium development and maintenance in male reproductive tract. In-depth analysis showed that Pkd1 is required to maintain tubulin cytoskeleton and important for Tgf-ß/Bmp signal transduction in epithelium of male reproductive tract. Altogether, our results for the first time provide direct evidence for developmental roles of Pkd1 in the male reproductive tract and provide new insights in reproductive tract abnormalities and infertility in ADPKD patients.

Structural analysis of testicular appendices in patients with cryptorchidism

Objectives Report the incidence and structure of testicular appendices (TAs) in patients with cryptorchidism, comparing their incidence with epididymal anomalies (EA) and patency of the vaginal process (PVP) and analyzes the structure of TAs. Material and Methods We studied 72 testes of patients with cryptorchidism (average of 6 years), and 8 testes from patients with hydroceles (average of 9 years). We analyzed the relations among the testis, epididymis and PVP and prevalence and histology of the TAs. The appendices of 10 patients with cryptorchidism and 8 with hydrocele were dissected and embedded in paraffin and stained with Masson trichrome; Weigert and Picro-Sirius Red with polarization and immunohistochemistry analysis of the collagen type III fibers to observe collagen. The stereological analysis was done with the software Image Pro and Image J, using a grid to determine volumetric densities (Vv). Means were statistically compared using the ANOVA and unpaired T test (p < 0.05). Results Of the 72 testes with cryptorchidism, 20 (27.77%) presented EA, 41 (56.9%) had PVP and 44 (61.1%) had TAs. Of the 44 testes with cryptorchidism and appendices, 30 (68.18%) presented PVP and 11 (25%) presented EA. There was no alteration of the epithelium in the appendices of patients in both groups. Stereological analysis documented the prevalence of ESFs (mean of 1.48%), prevalence of veins (mean of 10.11%) and decrease (p = 0.14) of SMCs in the TAs of patients with cryptorchidism (mean = 4.93%). Collagen III prevailed in the TAs of patients with cryptorchidism. Conclusion The testicular appendices presented significant structural alteration in the patients with cryptorchidism, indicating that TAs present a structural remodeling. .

Intrahepatic paratesticular cyst: unique presentation of vestigial remnants of Wolffian duct.

To report on a case of a progressively enlarging intrahepatic cyst in a 1-year-old boy who also presented with bilateral undescended testes. At surgery, the lesion emerged from the anterior surface of the liver but was unexpectedly found to arise from the epididymis of the right testis, which was located intra-abdominally. The histologic findings were consistent with a paratesticular cyst of vestigial remnants derived from the Wolffian duct. Such an unusual event has not been previously reported among the possible location of a paratesticular cyst, nor has it been described in the differential diagnosis of cystic lesions of the liver.

A survey of congenital reproductive abnormalities in rams in abattoirs in South west England.

Congenital abnormalities of the reproductive tract of male sheep were surveyed at three abattoirs in the south west of England during the period June 2000-January 2004. A total of 7307 rams were examined [6521 lambs (prepubescent) and hoggets (aged from their first autumn after birth until first shorn) and 786 adult rams mature rams that had been exposed to ewes]. A total of 156 congenital lesions were detected, 87 of which occurred in lambs. Testicular hypoplasia was the most common lesion occurring in 69 lambs as well as eight hoggets ('microtestes' were recognized in nine other animals in which the testis was disproportionately smaller than the epididymis). The second most common lesion found was notched scrotum occurring in 34 animals (27 young rams and seven adults). Some cases of notched scrotum were accompanied by hypospadias which was seen in a total of seven lambs and eight hoggets. Other lesions, detected in five or less animals (less than approximately 0.05% of the animals examined), included cryptorchidism and various abnormalities of the epididymis (segmental aplasia of the epididymis, blind efferent ducts and epididymal cyst) and congenital scrotal hernia. The overall prevalence of congenital lesions of 2.21% emphasizes the importance of undertaking breeding soundness examinations of young rams before they are put with the flock.

Findings concerning testis, vas deference, and epididymis in adult cases with nonpalpable testes

In this study, we aimed to state the relationship between testis, epididymis and vas deference, in adult cases with nonpalpable testis. Between January 1996 and December 2009, we evaluated 154 adult cases with nonpalpable testes. Mean age was 23 years (20-27 years). Explorations were performed by open inguinal incision, laparoscopy, and by inguinal incision and laparoscopy together on 22, 131 and 1 patient, respectively. Of all the unilateral cases, 32 were accepted as vanishing testis. In five of these cases, vas deference was ending inside the abdomen, and in the others, it was ending inside the scrotum. In the remaining 99 unilateral and 22 bilateral cases, 143 testes were found in total. Testes were found in the inguinal canal as atrophic in one case, at the right renal pedicle level with dysmorphic testis in one case, and anterior to the internal ring between the bladder and the common iliac vessels at a smaller than normal size in 119 cases. One (0.69 percent) case did not have epididymis. While epididymis was attached to the testis only at the head and tail locations in 88 (61.53 percent) cases, it was totally attached to the testis in 54 (37.76 percent) cases. There is an obviously high incidence rate of testis and vas deference anomalies, where epididymis is the most frequent one. In cases with abdominal testes, this rate is highest for high localised abdominal testes.

Histological findings in patients with cryptorchidism and testis-epididymis nonfusion.

PURPOSE: Fusion anomalies of the testis and epididymis are associated with cryptorchidism. The bilateral histology of the cryptorchid testis associated with the nonfused epididymis has not been reported previously. MATERIALS AND METHODS: We retrospectively reviewed patients who presented with unilateral undescended testes and underwent bilateral testis biopsy at orchiopexy between 1982 and 2008. Testes were stratified into groups based on degree of testis-epididymis nonfusion. Age at surgery, testicular volume, testicular position, total germ cells per tubule and adult dark spermatogonia per tubule were compared among all groups. RESULTS: A total of 2,660 testes were eligible for review, of which 2,425 had normal fusion (group 1), 55 had epididymal head nonfusion (group 2), 119 had epididymal tail nonfusion (group 3) and 61 had complete nonfusion (group 4). With increasing degrees of nonfusion trends toward younger age, smaller testicular volume and higher preoperative position were observed. However, testis-epididymis nonfusion was not a significant predictor of abnormal germ cells per tubule or adult dark spermatogonia per tubule in undescended testes and contralateral descended testes. CONCLUSIONS: Fusion anomalies are associated with smaller, higher testes with no significant abnormalities in germ cells per tubule or adult dark spermatogonia per tubule. Testis-epididymis nonfusion is not a reliable predictor of reduced histological findings, and should not be a strong consideration when counseling patients and their families about future fertility, especially in instances of complete nonfusion.

Swine models of cystic fibrosis reveal male reproductive tract phenotype at birth.

Nearly all male cystic fibrosis (CF) patients exhibit tissue abnormalities in the reproductive tract, a condition that renders them azoospermic and infertile. Two swine CF models have been reported recently that include respiratory and digestive manifestations that are comparable to human CF. The goal of this study was to determine the phenotypic changes that may be present in the vas deferens of these swine CF models. Tracts from CFTR(-/-) and CFTR(ΔF508/ΔF508) neonates revealed partial or total vas deferens and/or epididymis atresia at birth, while wild-type littermates were normal. Histopathological analysis revealed a range of tissue abnormalities and disruptions in tubular organization. Vas deferens epithelial cells were isolated and electrophysiological results support that CFTR(-/-) monolayers can exhibit Na(+) reabsorption but reveal no anion secretion following exposure to cAMP-generating compounds, suggesting that CFTR-dependent Cl(-) and/or HCO(3)(-) transport is completely impaired. SLC26A3 and SLC26A6 immunoreactivities were detected in all experimental groups, indicating that these two chloride-bicarbonate exchangers were present, but were either unable to function or their activity is electroneutral. In addition, no signs of increased mucus synthesis and/or secretion were present in the male excurrent ducts of these CF models. Results demonstrate a causal link between CFTR mutations and duct abnormalities that are manifested at birth.

Findings concerning testis, vas deference, and epididymis in adult cases with nonpalpable testes.

In this study, we aimed to state the relationship between testis, epididymis and vas deference, in adult cases with nonpalpable testis. Between January 1996 and December 2009, we evaluated 154 adult cases with nonpalpable testes. Mean age was 23 years (20-27 years). Explorations were performed by open inguinal incision, laparoscopy, and by inguinal incision and laparoscopy together on 22, 131 and 1 patient, respectively. Of all the unilateral cases, 32 were accepted as vanishing testis. In five of these cases, vas deference was ending inside the abdomen, and in the others, it was ending inside the scrotum. In the remaining 99 unilateral and 22 bilateral cases, 143 testes were found in total. Testes were found in the inguinal canal as atrophic in one case, at the right renal pedicle level with dysmorphic testis in one case, and anterior to the internal ring between the bladder and the common iliac vessels at a smaller than normal size in 119 cases. One (0.69%) case did not have epididymis. While epididymis was attached to the testis only at the head and tail locations in 88 (61.53%) cases, it was totally attached to the testis in 54 (37.76%) cases. There is an obviously high incidence rate of testis and vas deference anomalies, where epididymis is the most frequent one. In cases with abdominal testes, this rate is highest for high localised abdominal testes.