Scrotal Testes Research Articles

Sertoli Cell Development and Function in an Animal Model of Testicular Dysgenesis Syndrome1

Pregnancy exposure to di(n-butyl) phthalate (DBP) in rats induces a testicular dysgenesislike syndrome (TDS) in male offspring. Earlier studies suggested altered Sertoli cell development/maturation may result, especially in testes that become cryptorchid. This study quantitatively assessed Sertoli cell numerical and functional development in DBP-exposed rats and compared (unilaterally) cryptorchid and scrotal testes. Pregnant rats were gavaged with 500 mg/kg/day DBP or corn oil from embryonic (E) Days 13.5 to 21.5. Male offspring were sampled on E21.5 or Postnatal Day 6, 10, 15, 25, or 90. Sertoli cell number in DBP-exposed males was reduced by approximately 50% at E21.5 but recovered to normal by Days 25-90, accompanied by significant changes in plasma inhibin B and testosterone levels. Sertoli cell maturational development in DBP-exposed males, assessed using five protein markers (anti-müllerian hormone, cytokeratin, androgen receptor, CDKN1B, and Nestin), was largely normal, with some evidence of delayed maturation. However, in adulthood, Sertoli cells (SC) in areas lacking germ cells (Sertoli cell-only [SCO] tubules) often exhibited immature features, especially in cryptorchid testes. Sertoli cells in DBP-exposed animals supported fewer germ cells during puberty, but this normalized in scrotal testes by adulthood. Scrotal and especially cryptorchid testes from DBP-exposed animals exhibited abnormalities (SCO tubules, focal dysgenetic areas) at all postnatal ages. Cryptorchid testes from DBP-exposed animals exhibited more Sertoli cell abnormalities at Day 25 compared with scrotal testes, perhaps indicating more severe underlying Sertoli cell malfunction in these testes. Our findings support the concept of altered Sertoli cell development in TDS, especially in cryptorchid testes, but show that maturational defects in Sertoli cells in adulthood most commonly reflect secondary dedifferentiation in absence of germ cells.

A novel congenital ichthyosiform syndrome with associated panhypopituitarism, corneal opacities and mental retardation

A 15-year-old male presented with ichthyosis since infancy with panhypopituitarism, short stature and knock-knees, delayed puberty, high scrotal retractile testes, mental retardation and corneal opacities. He developed recurrent tinea capitis and tinea corporis. The clinical symptomatology indicates that this case cannot be considered as a subtype of inherited ichthyosis group, but suggests a new syndrome as a separate nosologic entity. Two previously reported cases with possibly the same syndrome also had ichthyosis associated with variable endocrinopathy. Thorough endocrinological evaluation and appropriate intervention in patients of ichthyosis with short stature may reduce the morbidity associated with retarded skeletal growth and gonadal maturation.

Surgical Treatment of Unilaterally Undescended Testes: Testicular Growth After Randomization to Orchiopexy at Age 9 Months or 3 Years

We compared the growth of congenital, unilaterally undescended testes following orchiopexy at age 9 months or 3 years. Patients were randomized to surgery at age 9 months (72) or 3 years (83). Testicular volume was measured by ultrasonography at ages 6, 12, 24, 39 and 48 months. Orchiopexy at age 9 months resulted in an increase in testicular volume at subsequent measurements at ages 2, 3 and 4 years compared to the volume at 6 months (p <0.001). In contrast, no significant growth was noted in the group treated at age 3 years. The improved testicular growth after early orchiopexy was also demonstrated by a gradual increase in the ratio of the previously retained testis and the scrotal testis in individual boys from 6 months to 4 years (0.68 to 0.81, p <0.001). For the late treatment group a significant decrease in this ratio was noted during the same period (0.68 to 0.56, p <0.01). Surgical treatment at 9 months resulted in partial catch-up of testicular growth until at least age 4 years compared to surgery at 3 years, clearly indicating that early surgery has a beneficial effect on testicular growth. Since testicular volume is an approximate indirect measure of spermatogenic activity, this gives hope that orchiopexy at this age may improve future spermatogenesis.

Early one-stage total phalloplasty in infants with aphallia

Purpose Aphallia is a rare and dramatic malformation, traditionally committed to gender reassignement. The aim of the video is to present a surgical procedure for early, one-stage, total phalloplasty and complete urethroplasty, designed for infants affected by aphallia. Material and methods This is a case of a 7 month-old boy born with aphallia, low-anorectal-malformation and rectal-urethra, kariotype 46 XY and bilateral scrotal testis. Recurrent orchiepididymitis also occurred. Results Sagittal-transanorectal-approach, in prone-knee-chest-position, was first used to divide the rectal-urethra and performe an anoplasty. Turned to supine-lithotomy-position, total phalloplasty was performed using a quadrangular 6 x 6 cm wide abdominal skin flap; complete urethroplasty with a tubularized buccal-mucosa free-graft, 9 cm long, was performed. The buccal-mucosa-tube was sutured end-to-end to the posterior urethra. Short-term outcome is excellent, with high parental satisfaction. Conclusions The opposite gender should not be assigned to patients affected by aphallia that are better raised according to their male kariotype and hormonal pattern. Definitive forearm micro-vascular phalloplasty has shown good results in adults, but it is generally not performed in pre-pubertal boys. Despite the absence of corpora cavernosa in the constructed phallus, social and psychological reasons justify early phalloplasty. Pryor described quadrangular lower abdominal skin-flaps in adulthood for both penile and urethral reconstruction. We preferred buccal mucosa graft for the urethral reconstruction. Long term follow-up is needed to evaluate the results of this technique at puberty in patients with aphallia and in other cases of severe deficit of the male external genitalia.

ANNUAL CYCLES IN BODY MASS AND REPRODUCTION OF CHIRICAHUA FOX SQUIRRELS (SCIURUS NAYARITENSIS CHIRICAHUAE)

Abstract The Chiricahua fox squirrel (Sciurus nayaritensis chiricahuae) is an uncommon subspecies endemic to the Chiricahua Mountains of southeastern Arizona. We monitored annual cycles of body mass and reproduction to elucidate factors shaping the ecology of the sexes. Body mass of adult males did not fluctuate seasonally, although males tended to be heavier in winter. Body mass of adult females fluctuated seasonally, with lower body masses in summer than winter. Males and females did not differ in body mass in summer and fall, but females were heavier than males in winter and spring. Males with scrotal testes were found in the population during all seasons, but were especially prevalent in winter and spring. The majority of lactating females were present in spring and summer. Annual cycles in reproduction and body mass of Chiricahua fox squirrels are similar to more widespread species of tree squirrels, although males did not exhibit typical body mass fluctuations. Extreme spatial and temporal fluctuati...

OBSERVATIONS ON THE ECOLOGY OF THE ENDEMIC MEARNS'S SQUIRREL (TAMIASCIURUS MEARNSI)

Mearns's squirrel (Tamiasciurus mearnsi) is an endemic species of the montane forest of the Sierra de San Pedro Mártir in Baja California. Despite having been described for the first time in 1893 and a listing as threatened by Mexican authorities, no information is available on the ecology of this southernmost Tamiasciurus. We observed the ecology of Mearns's squirrels during 2004 and 2005. Mearns's squirrel apparently does not form larderhoards, known as middens, or leaf nests commonly built by other members of this genus. We observed Mearns's squirrels to feed heavily on tree seeds and fungi. We noted males with scrotal testes and a female in estrus in late spring. We did not observe eastern gray squirrels (Sciurus carolinensis), introduced to the western Sierra in 1946, within the areas that we searched for T. mearnsi. Mearns's squirrels might possess unique adaptations for their persistence in the dry, open forest of the Sierra de San Pedro Mártir.

Acute and Long-Term Effects ofin UteroExposure of Rats to Di(n-Butyl) Phthalate on Testicular Germ Cell Development and Proliferation

This study investigated effects of in utero exposure [embryonic day (e)13.5-e21.5] to di(n-butyl) phthalate (DBP) on fetal gonocytes and postnatal germ cell (GC) development in rats and focused on changes (delayed development) relevant to the postulated origins of human carcinoma-in situ cells. DBP treatment resulted in both early (e15.5-e17.5) and late (e19.5-e21.5) effects on gonocytes. The former involved delayed entry of proliferating gonocytes into quiescence, as indicated by prolongation/overexpression of octamer-binding transcription factor 3/4 and retinoblastoma protein phosphorylated at Ser 807/811 and Ki67 plus a 2- to 4-fold increase in gonocyte apoptosis. The late effect of DBP was to induce a greater than 10-fold increase in occurrence of multinucleated gonocytes. GC numbers in DBP-exposed males were reduced (P < 0.01) by 37, 53, 79, and 80% at e21.5 and postnatal d (d) 4, 8, and 15, respectively, with recovery to normal in scrotal testes between postnatal d 25 and 90. The DBP-induced decrease in GC numbers at d 4-8 was associated with delayed exit from quiescence, as indicated by retinoblastoma protein expression and a 28% reduction (P < 0.001) in GC proliferation index at d 6, although the latter was increased by 84% at d 25. The postnatal GC changes were associated with the early, but not late, effects of DBP on gonocytes as short-term DBP treatment from e19.5 to e20.5, induced multinucleated gonocytes as effectively as did treatment from e13.5 to e20.5, but did not reduce GC numbers on d 4. In conclusion, fetal DBP exposure delays normal GC development in both fetal (as early as e15.5) and postnatal life with the possibility of consequences for fertility.

The high scrotal (“gliding”) testis revised

At present, the high scrotal testis is considered a distinct and separate entity of undescended testis. The aim of this study was to assess whether high scrotal testis is actually either a congenital- or acquired-undescended testis. In 527 consecutive boys (aged 0.4 to 16.5 years, mean 7.5) referred for non-scrotal testis, the number of high scrotal testis was prospectively determined. According to previous testis position, the high scrotal testis was classified into congenital- and acquired-high scrotal testis. In congenital-high scrotal testis orchidopexy was performed whereas spontaneous descent at puberty was awaited in acquired-high scrotal testis. In 210 testes, the gonad was diagnosed as high scrotal. In six testes the condition was congenital and 204 testes were diagnosed as acquired. All cases of congenital-high scrotal testis were treated surgically. In 100 acquired-high scrotal testis follow-up was performed. Of these, 75 testes descended spontaneously at puberty. We propose that the high scrotal testis should be regarded, not as a distinct and separate entity, but as a part of the spectrum of either congenital-undescended testis or acquired-undescended testis. Since spontaneous descent can occur at puberty in acquired-high scrotal testis, therapy may be different between both forms.

Further evidence for acquired undescended testicle in the UK and its incompatibility with current recommendations in the Hall Report

Objective The 4th edition of the Hall Report [Hall DMB. Health for all children. Oxford: Oxford University Press; 2003. p. 167] does not expect undiagnosed undescended testicles at the age of 5 years or subsequently to be seen if its advice for diagnosis is carried out. We examine whether that recommendation can be relied upon. Method A retrospective audit was performed of 228 boys who underwent orchidopexy between January 1992 and December 2003 at the County Hospital Hereford, UK. During that time, 10,048 boys were born at the hospital. Child health records, hospital records and some GP records were used. Results A total of 103 boys (45%) were treated before their 5th birthday and 125 (55%) were treated after the age of 5; 93 orchidopexies were performed as a result of diagnosis made at birth or 6 weeks, but 83 were undertaken in boys documented as having scrotally placed testes both at birth and 6 weeks. A further 21 had documentation for scrotal testes either at birth (14) or at 6 weeks (7) but not both. The records of the remaining 31 are either missing or did not yield the information required largely because the Parent Held Child Record was introduced after their time. The literature was reviewed, and the results found to concur with those of other papers, in particular with a recent study from The Netherlands, which led to a new classification of undescended testis drawing attention to ‘acquired undescended testicle’. The progressive nature of this entity was seen from review of the case notes. Conclusion The natural history of acquired undescended testis means that recommendations as set out in the Hall Report “that no further check after six weeks need be made if the testes are ‘well down’ at that stage” cannot be successful, and all concerned in childhood surveillance will need to be aware of this and remain vigilant at least until puberty. Perhaps a prospective study following the Netherlands design should be undertaken in this country.

Testicular growth from birth to two years of age, and the effect of orchidopexy at age nine months: A randomized, controlled study

AbstractAim: To study whether surgical treatment at age 9 mo in boys with congenital unilaterally palpable undescended testes (cryptorchidism) is followed by improved growth of the previously retained testes compared to non‐treatment. Methods: At the age of 6 mo, 70 boys were randomized to surgical treatment at 9 mo and 79 boys to treatment at 3 y of age. The boys were then followed at 12 and 24 mo. Ultrasonography was used to determine testicular volume. Results: After orchidopexy, the previously retained testes resumed growth and were significantly larger than the non‐operated testes at 2 y (0.49 ml vs 0.36 ml, p&lt;0.001). Testicular growth after orchidopexy was also demonstrated by a higher mean ratio between the previously retained and the scrotal testes of the individual boys at 2 y: 0.84 for the surgically treated group, compared to 0.63 for the untreated group (p&lt;0.001).Conclusion: Surgery at 9 mo has a beneficial effect on the growth of previously undescended testes.

Testicular growth from birth to two years of age, and the effect of orchidopexy at age nine months: A randomized, controlled study

To study whether surgical treatment at age 9 mo in boys with congenital unilaterally palpable undescended testes (cryptorchidism) is followed by improved growth of the previously retained testes compared to non-treatment. At the age of 6 mo, 70 boys were randomized to surgical treatment at 9 mo and 79 boys to treatment at 3 y of age. The boys were then followed at 12 and 24 mo. Ultrasonography was used to determine testicular volume. After orchidopexy, the previously retained testes resumed growth and were significantly larger than the non-operated testes at 2 y (0.49 ml vs 0.36 ml, p<0.001). Testicular growth after orchidopexy was also demonstrated by a higher mean ratio between the previously retained and the scrotal testes of the individual boys at 2 y: 0.84 for the surgically treated group, compared to 0.63 for the untreated group (p<0.001). Surgery at 9 mo has a beneficial effect on the growth of previously undescended testes.

Differential development of ectopic testes based on their location in rats

Objective In order to investigate the effect of location on the development of ectopic testes, the relationship between the degree of degenerative change in ectopic testes and their original position was examined in rat models of cryptorchidism. Materials and methods Unilateral ectopic testes were created by excising the future scrotal skin on either the right or left side in newborn rats. At 60 days of age, the position of the testes was examined, the testicular weight and seminiferous tubular diameter (STD) were measured, and spermatogenesis was evaluated using the Johnsen score. Results All the rats showed maldescended testes on the operated side, with the testes descending into the superficial inguinal pouch, the perineum or the transverse contralateral scrotum. The testicular weight, STD and Johnsen score were all significantly lower for the superficial inguinal testes than for either the perineal or contralateral scrotal testes. Conclusion These findings suggest that the degree of testicular degeneration depends on the position of the ectopic testes; the higher the testicular location, the greater the histological changes.

Hermaphroditism: cytogenetics, gonadal pathology and gender assignment a case report

True hermaphroditism is a rare intersex disorder in which individuals possess both testicular and ovarian gonadal tissue. A case of true unilateral hermaphroditism presenting with ambiguous external genitalia, right scrotal testis and left pelvic ovotestis is herein outlined Phallic, gonadal and genetic factors were considered before male gender was assigned. Gender assignment procedures have been questioned by intersex activists opposed to early genital surgery. Western societies have a binary perspective on gender and this leads to a stigma being placed on intersex cases. A multidisciplinary approach to this problem involving paediatric specialists in the field, of endocrinology, surgery and psychiatry is necessary, along with educational programmes that promote tolerance in society to variations in gender.

Alterations in the Immunohistochemical Localization Patterns of .ALPHA.-Smooth Muscle Actin (SMA) and Vimentin in the Postnatally Developing Bovine Cryptorchid Testis

Previously, we reported the normal postnatal developmental changes in immunohistochemical localization of alpha-smooth muscle actin (SMA) and vimentin in the bovine testis. In this study, we demonstrate the alterations of these cytoskeletal proteins in the bovine cryptorchid testis as compared to the contralateral scrotal testis during postnatal development. Seminiferous peritubular alpha-SMA did not appear in the cryptorchid testis until 8 months of age, except for very weak intermittent filaments in relatively larger seminiferous tubules. However, a similar peritubular pattern was observed in the 18-month-old cryptorchid and scrotal testes. Moreover, weak expression of alpha-SMA in the straight tubules and rete testes at 5 months of age did not improve until 18 months of age in the cryptorchid testes. The Sertoli cell vimentin in the cryptorchid testes revealed a highly immature pattern at 5 months of age, a pattern similar to a transforming pattern with infranuclear vimentin extensions at 8 months of age, and a pattern that was almost a transforming pattern, but with considerable weakening of the vimentin filaments, at 18 months of age. In conclusion, cryptorchidism may cause considerable delay in testicular myoid cell differentiation and in attainment of the transforming pattern of the Sertoli cell vimentin, which weakens and fails to attain the mature pattern in the cryptorchid testis. These alterations may be related to the structural immaturity and functional failure of postnatally developing bovine testes exposed continuously to body heat.

Germ cell apoptosis induced by experimental cryptorchidism is mediated by multiple molecular pathways in Cynomolgus Macaque

Experimental cryptorchidism is a common model for examining the expression and function of heat-sensitive spermatogenesis-related genes in testis. Previous studies have shown that germ cells in cryptorchid testis die mainly in an apoptotic way. The molecular mechanism, however, is still unclear. We have established unilateral cryptorchid monkey model (Cynomolgus Macaque) to identify possible molecules involved in the germ cell apoptosis. The degree of germ cell apoptosis, the morphology of the cryptorchid testis, and the changes in the serum concentration of FSH, LH and testosterone after cryptorchid surgery were analyzed. Sertoli cell marker molecule vimentin, the orphan receptor LRH-1, as well as the mitochondria-related protein HSP60 and Bcl-2 were examined. Our results showed that the weight of the cryptorchid testis decreased in a time-dependent manner started from day 7 after the surgery, while the weight of the scrotal testis had no obvious change. HE staining showed that from day 5, some germ cells were detached from the epithelium. A massive degeneration of the seminiferous epithelium characteristic of epithelial structural disorganization and the formation of multinucleated giant cells as well as vacuoles was observed on day 10 and 15. The cryptorchidism induced a marked germ cell apoptosis on day 3 after the operation, reaching a peak level on day 7.

A rare diagnosis: testicular dysgenesis with carcinoma in situ detected in a patient with ultrasonic microlithiasis

A rare case is presented where a dysgenetic testis with microinvasive carcinoma in situ (CIS, also known as intratubular germ cell neoplasm of unclassified type [IGCNU] and testicular intraepithelial neoplasia [TIN]) with microinvasion to rete testis and the interstitial tissue was found in a 32-year-old man presenting with mild scrotal pain and ultrasonic testicular microlithiasis. Knowledge of the association of ultrasound and CIS is important to diagnose patients at the stage prior to development of an overt germ cell tumor. The patient had three of four disorders considered symptoms of the testicular dysgenesis syndrome (TDS): a dysgenetic left testicle with CIS, a mild left-sided cryptorchidism (high positioned scrotal hypotrophic testis) and a slightly reduced semen quality. Therefore, it should be kept in mind that a patient with one TDS symptom may harbour the other, even CIS or testicular cancer. Accordingly, patients with one TDS symptom ought to be examined for the presence of the others, and if more that one is present, extra concern is warranted.

Hypospadias in three calves: a case report

Two to three weeks old 3 male indigenous Korean calves weighing 35&amp;ndash;40 kg were referred to the Animal Medical Centre,ChonbukNationalUniversitywith signs of urine scalding on the ventral perineum. Physical examination in all 3 cases revealed aplasia of the penis along with an undescended testis, bifid scrotum and ventrally incomplete sheath. In case 1, the urethra opened cranially to the bifid scrotum, whereas in case 2 and 3, the urethra opened at the ventral perineum. The diagnosis was made as hypospadias, along with penile aplasia and unilateral cryptorchidism. With an exploratory laparotomy, the abdominal testis was removed. The scrotal testis was also castrated and scrotal ablation was performed. In case 1, prescrotal urethrostomy and in case 2 and 3, perineal urethrostomy was performed. Two weeks after surgical correction, the caves appeared to be urinating normally.

Testis and Antler Dysgenesis in Sitka Black-Tailed Deer on Kodiak Island, Alaska: Sequela of Environmental Endocrine Disruption?

It had been observed that many male Sitka black-tailed deer (Odocoileus hemionus sitkensis) on Kodiak Island, Alaska, had abnormal antlers, were cryptorchid, and presented no evidence of hypospadias. We sought to better understand the problem and investigated 171 male deer for phenotypic aberrations and 12 for detailed testicular histopathology. For the low-lying Aliulik Peninsula (AP), 61 of 94 deer were bilateral cryptorchids (BCOs); 70% of these had abnormal antlers. Elsewhere on the Kodiak Archipelago, only 5 of 65 deer were BCOs. All 11 abdominal testes examined had no spermatogenesis but contained abnormalities including carcinoma in situ–like cells, possible precursors of seminoma; Sertoli cell, Leydig cell, and stromal cell tumors; carcinoma and adenoma of rete testis; and microlithiasis or calcifications. Cysts also were evident within the excurrent ducts. Two of 10 scrotal testes contained similar abnormalities, although spermatogenesis was ongoing. We cannot rule out that these abnormalities are linked sequelae of a mutation(s) in a founder animal, followed by transmission over many years and causing high prevalence only on the AP. However, based on lesions observed, we hypothesize that it is more likely that this testis–antler dysgenesis resulted from continuing exposure of pregnant females to an estrogenic environmental agent(s), thereby transforming testicular cells, affecting development of primordial antler pedicles, and blocking transabdominal descent of fetal testes. A browse (e.g., kelp) favored by deer in this locale might carry the putative estrogenic agent(s).

Polyorchidism and torsion. A lesson from 2 cases

Two cases of polyorchidism with 2 left scrotal testes are referred. In both patients, the segmented gonads showed a “bell clapper” deformity. In the first patient, the contralateral gonad also presented a large mesorchium and absence of scrotal ligament, whereas in the second case, the right gonad was firmly adhered to the tunica vaginalis because of a previous appendix testis torsion. Orchidopexy of all testes, judged at risk for torsion, was performed. Contrary to what is recommended by recent literature, we consider scrotal exploration and testis fixation mandatory of the contralateral, apparently normal gonad as well, even in the absence of clinical and ultrasound signs of associated abnormalities or complications.

Proliferation and apoptosis of spermatogonia in postpuberal boar ( Sus domesticus) testes with spontaneous unilateral and bilateral abdominal cryptorchidism

Cryptorchidism is a frequent male sexual disorder in mammals, which affects the histology of the tunica propria, interstitial tissue, blood vessels, seminiferous epithelium and testis functioning. In this paper, proliferation and apoptosis were examined in the seminiferous epithelium of both testes from unaffected boars and from boars suffering unilateral and bilateral cryptorchidism. In germ cells, proliferation was studied using the immunohistochemical PCNA technique, and apoptosis was analysed by in situ TUNEL labelling. An index was obtained for the proliferation and apoptosis observed in seminiferous tubules. In abdominal testes the epithelium contained few spermatogonia and Sertoli cells. In the testes of unaffected boars, numerous spermatogonia proliferated, whereas in cryptorchid testes such proliferation was lower and the proliferation/apoptosis ratio diminished. In the unaffected group, the TUNEL-positive germ cells were spermatogonia and spermatocytes in different phases of meiosis. In abdominal testes, the TUNEL-positive germ cells were spermatogonia alone. The apoptosis index of both abdominal and scrotal testes was similar. In conclusion, spontaneous cryptorchid testes showed a lower rate of spermatogonia proliferation in the seminiferous epithelium.