Hideyuki Kamisawa

Findings of fat-suppressed T2-weighted and diffusion-weighted magnetic resonance imaging in the diagnosis of non-palpable testes

Study Type – Diagnostic (exploratory cohort)
Level of Evidence 2b

Expression profiling of microRNA in cryptorchid testes: miR-135a contributes to the maintenance of spermatogonial stem cells by regulating FoxO1.

PURPOSE We elucidated the mechanism of spermatogonial stem cell disturbance of cryptorchidism and investigated the expression of miRNAs and their target genes in undescended testes. MATERIALS AND METHODS Using microarray analysis we compared total miRNA expression in unilateral undescended testes with that in contralateral descended and normal testes in a rat model of cryptorchidism. The model was derived by administering flutamide to pregnant Sprague Dawley® rats. We identified mRNA targets of miRNAs by bioinformatic analysis, followed by in situ hybridization and immunohistochemistry to localize candidate miRNAs and mRNAs, respectively. We also investigated whether miRNAs could inhibit target protein expression in vitro. RESULTS Microarray analysis and subsequent quantitative reverse transcriptase-polymerase chain reaction showed that only miR-135a was expressed at a lower level in undescended testes. We identified its target as FoxO1, which is essential for stem cell maintenance. miR-135a and FoxO1 localized to spermatogonial stem cells. FoxO1 localized to the spermatogonial stem cell nucleus less frequently in undescended testes, indicating that the activity of FoxO1, which acts as a transcription factor, is altered in undescended testes. Finally, miR-135a transfection into spermatogonia in vitro resulted in down-regulation of FoxO1 expression. CONCLUSIONS In cryptorchid testes there is a decreased number of spermatogonial stem cells in which FoxO1 is activated, indicating that failure of spermatogonial stem cell maintenance results in spermatogenesis alteration. We also noted interaction between miR-135a and FoxO1, and propose that miR-135a contributes to spermatogonial stem cell maintenance through modulation of FoxO1 activity.

Extravesical robot-assisted laparoscopic ureteral reimplantation for vesicoureteral reflux: initial experience in Japan with the ureteral advancement technique.

To report our initial experience with robot‐assisted laparoscopic extravesical ureteral reimplantation using the ureteral advancement technique.

Optimal Cutoff Value of Contralateral Testicular Size for Prediction of Absent Testis in Japanese Boys With Nonpalpable Testis

OBJECTIVES To investigate the accuracy of contralateral testicular hypertrophy in Japanese boys with a nonpalpable testis and to determine the optimal cutoff value of the contralateral testicular size to predict the absence of the testis. METHODS From December 2003 to November 2009, we evaluated 55 boys <60 months old (mean age 19.4) with a unilateral nonpalpable testis and compared their findings with those of a control group. The control group included 20 age-matched boys with 40 testes. The nonpalpable status of the testes was diagnosed by physical examination, and the contralateral testis was measured with calipers before surgery. A sensitivity and specificity analysis were performed using computer software. RESULTS At surgery, the testis was found in 22 of the 55 boys and was absent in 33. Of the 33 boys with an absent testis, 4 had a blind-ending vessel and 29 had an atrophic cord and testicular nubbin in the canal or scrotum. The mean contralateral testicular length and volume in the boys with an absent testis was 22.4 mm and 2.20 cm(3) compared with 16.6 mm and 1.10 cm(3) in the boys with the testis present and 16.6 mm and 1.18 cm(3) in the controls, respectively (P < .01). The predictive accuracy, sensitivity, and specificity for an absent testis was 87.3%, 81.8%, and 95.5% for the length and 85.5%, 84.8%, and 86.4% for the volume, respectively, at the optimal cutoff value of 21 mm in length and 1.6 cm(3) in volume. CONCLUSIONS Our data have shown that contralateral testicular hypertrophy strongly indicates an absent testis in Japanese boys. The optimal cutoff for contralateral testicular hypertrophy with calipers was 21 mm and 1.6 cm(3). This result has provided valuable information for preoperative counseling and treatment planning.

Intratesticular pressure after testicular torsion as a predictor of subsequent spermatogenesis: a rat model

What’s known on the subject? and What does the study add?

Attenuation of Spermatogonial Stem Cell Activity in Cryptorchid Testes

PURPOSE To elucidate the mechanism of infertility caused by cryptorchidism we focused on early stage spermatogenesis and spermatogonial stem cell activity in undifferentiated spermatogonia in cryptorchid testes. MATERIALS AND METHODS Histological findings and expression patterns of the stem cell marker undifferentiated embryonic cell transcription factor 1 were examined in a unilateral cryptorchid rat model. We removed unilateral descended testis and contralateral descended testis from cryptorchid and normal rats (control), respectively, 18 days postcoitum to 144 days postpartum. RESULTS In descended testes gonocyte differentiation into early A spermatogonia occurred at 9 days postpartum. However, this transformation was altered in undescended testes. Furthermore, the undifferentiated embryonic cell transcription factor 1 negative early A spermatogonia-to-positive early A spermatogonia ratio was significantly higher in the undescended testis group (mean ± SD 0.69 ± 0.04) than in the control (0.46 ± 0.10, p = 0.037) and descended testis (0.44 ± 0.05, p = 0.022) groups, indicating decreased early A spermatogonia with spermatogonial stem cell activity in cryptorchid testes. CONCLUSIONS In cryptorchid testes the differentiation from gonocytes into early A spermatogonia and the stem cell activity of early A spermatogonia were altered during the early stage of spermatogenesis, suggesting that the loss of spermatogonial stem cell activity in cryptorchid rats resulted in altered spermatogenesis, thus interfering with fertility.

Altered Expression and Localization of Estrogen Receptors Alpha and Beta in the Testes of a Cryptorchid Rat Model

OBJECTIVES To assess the involvement of estrogen in spermatogenesis, we evaluated the expression of estrogen receptors (ERs) alpha (ERalpha) and beta (ERbeta) in the cryptorchid testes in model rats exposed to flutamide during the fetal stage. METHODS Cryptorchid model rats were produced by administering flutamide to pregnant Sprague-Dawley rats. To evaluate the sequential change in the expression of ERalpha and ERbeta genes, real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was performed using specific primers. Immunohistochemistry with ERalpha and ERbeta antibodies was performed, and the results were evaluated to determine the influences of orchiopexy. RESULTS Real-time RT-PCR revealed that ERalpha expression in control testes increases with growth and peaks value at 7 weeks and significantly decreases in cryptorchid testes. ERbeta expression was low, and there were no significant differences between both the cryptorchid and control testes groups. Immunohistochemistry revealed that ERalpha protein was present in the spermatids and Sertoli cells of descended testes, and that this protein was strongly expressed in the Leydig cells of cryptorchid testes. ERbeta was detected in multiple cells in both groups. After orchiopexy, ERalpha expression was detected in the spermatids of cryptorchid testes. CONCLUSIONS Spermatogenesis in cryptorchid rats is disrupted. Because the expression of ERbeta was unchanged in both control and cryptorchid testes, we supposed that alteration in ERalpha levels is more closely related to spermatogenic failure than ERbeta levels in the cryptorchid testes. We considered that increased expression of ERalpha in Leydig cells of cryptorchid testes is associated with estradiol level in the testicular tissue, and androgen-estrogen imbalance deteriorates spermatogenesis in cryptorchidism.

Genome-Wide Gene Expression Profiling of Randall’s Plaques in Calcium Oxalate Stone Formers

Randall plaques (RPs) can contribute to the formation of idiopathic calcium oxalate (CaOx) kidney stones; however, genes related to RP formation have not been identified. We previously reported the potential therapeutic role of osteopontin (OPN) and macrophages in CaOx kidney stone formation, discovered using genome-recombined mice and genome-wide analyses. Here, to characterize the genetic pathogenesis of RPs, we used microarrays and immunohistology to compare gene expression among renal papillary RP and non-RP tissues of 23 CaOx stone formers (SFs) (age- and sex-matched) and normal papillary tissue of seven controls. Transmission electron microscopy showed OPN and collagen expression inside and around RPs, respectively. Cluster analysis revealed that the papillary gene expression of CaOx SFs differed significantly from that of controls. Disease and function analysis of gene expression revealed activation of cellular hyperpolarization, reproductive development, and molecular transport in papillary tissue from RPs and non-RP regions of CaOx SFs. Compared with non-RP tissue, RP tissue showed upregulation (˃2-fold) of LCN2, IL11, PTGS1, GPX3, and MMD and downregulation (0.5-fold) of SLC12A1 and NALCN (P<0.01). In network and toxicity analyses, these genes associated with activated mitogen-activated protein kinase, the Akt/phosphatidylinositol 3-kinase pathway, and proinflammatory cytokines that cause renal injury and oxidative stress. Additionally, expression of proinflammatory cytokines, numbers of immune cells, and cellular apoptosis increased in RP tissue. This study establishes an association between genes related to renal dysfunction, proinflammation, oxidative stress, and ion transport and RP development in CaOx SFs.

Feasible etiology of vanishing testis regarding disturbance of testicular development: Histopathological and immunohistochemical evaluation of testicular nubbins

Objectives:  To identify the causes of vanishing testis besides vascular events secondary to testicular torsion.

A Japanese View on Circumcision: Nonoperative Management of Normal and Abnormal Prepuce

Circumcision is generally undertaken for 3 reasons; first, as an item of religious practice, typically neonatally, although occasionally transpubertally, as a rite of passage; second, as a prophylactic measure against future ailments (for the reduction in the risk of penile cancer, urinary tract infection, and sexually transmitted disease); and third, for immediate medical indication. There are many different views worldwide on circumcision; we are presenting a Japanese view on the management of pediatric foreskin.