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This study aimed to evaluate the ability of rete testis thickness (RTT) and testicular shear wave elastography (SWE) to differentiate obstructive azoospermia (OA) from nonobstructive azoospermia (NOA). We assessed 290 testes of 145 infertile males with azoospermia and 94 testes of 47 healthy volunteers at Shanghai General Hospital (Shanghai, China) between August 2019 and October 2021. The testicular volume (TV), SWE, and RTT were compared among patients with OA and NOA and healthy controls. The diagnostic performances of the three variables were evaluated using the receiver operating characteristic curve. The TV, SWE, and RTT in OA differed significantly from those in NOA (all P ≤ 0.001) but were similar to those in healthy controls. Males with OA and NOA were similar at TVs of 9-11 cm3 (P = 0.838), with sensitivity, specificity, Youden index, and area under the curve of 50.0%, 84.2%, 0.34, and 0.662 (95% confidence interval [CI]: 0.502-0.799), respectively, for SWE cut-off of 3.1 kPa; and 94.1%, 79.2%, 0.74, and 0.904 (95% CI: 0.811-0.996), respectively, for RTT cut-off of 1.6 mm. The results showed that RTT performed significantly better than SWE in differentiating OA from NOA in the TV overlap range. In conclusion, ultrasonographic RTT evaluation proved a promising diagnostic approach to differentiate OA from NOA, particularly in the TV overlap range.

Seminiferous tubules (STs) in the mammalian testes are connected to the rete testis (RT) via a Sertoli valve (SV). Spermatozoa produced in the STs are released into the tubular luminal fluid and passively transported through the SV into the RT. However, the physiological functions of the RT and SV remain unclear. Here, we identified the expression of Sox17 in RT epithelia. The SV valve was disrupted before puberty in RT-specific Sox17 conditional knockout ( Sox17- cKO) male mice. This induced a backflow of RT fluid into the STs, which caused aberrant detachment of immature spermatids. RT of Sox17- cKO mice had reduced expression levels of various growth factor genes, which presumably support SV formation. When transplanted next to the Sox17 + RT, Sertoli cells of Sox17- cKO mice reconstructed the SV and supported proper spermiogenesis in the STs. This study highlights the novel and unexpected modulatory roles of the RT in SV valve formation and spermatogenesis in mouse testes, as a downstream action of Sox17 . A valve-like structure called this Sertoli valve (SV) supports spermatogenesis by modulating the directional fluid flow in mouse testis. The SV formation is supported by its neighboring SOX17 + rete testis (RT). This study highlights the essential roles of RT and SV in spermatogenesis.

The rete ovarii and epoophoron in females are homologous structures of the rete testis and efferent/epididymal duct in males and are derived from the developing rete cells and mesonephric tubules, respectively. Sex steroid hormones play a critical role in reproductive function for both sexes, and we recently reported expression patterns of sex steroid receptors in developing male reproductive tracts. However, their expression patterns in females remain unclear. We, therefore, investigated the three-dimensional structure and expression patterns of sex steroid receptors in the rete ovarii and epoophoron of fetal and adult female mice. In adult females, the epoophoron was not adherent to the rete ovarii. The rete ovarii had a bursa-like structure, with its extra-ovarian region protruding toward the epoophoron. A marker for mesonephric tubules, PAX2 (Paired box 2), was detected in the epoophoron and a small population of epithelial cells in the extra-ovarian rete ovarii. These epithelial cells expressed estrogen receptor and androgen receptor. During development, mesonephric tubules were adherent to the rete ovarii at first, but as the development proceeded, the continuity was lost due to the interruption of the tubule rather than separation between the tip of the tubule and rete ovarii. These findings suggest that epithelial cells, originating from the mesonephric tubules, persist even in the adult rete ovarii with maintained expressions of receptors for estrogen and androgen.

The reproductive homeobox X-linked (Rhox) genes encode transcription factors that are expressed selectively in reproductive tissues including the testis, epididymis, ovary, and placenta. While many Rhox genes are expressed in germ cells in the mouse testis, only Rhox8 is expressed exclusively in the Sertoli cells during embryonic and postnatal development, suggesting a possible role of Rhox8 in embryonic gonad development. Previously, Sertoli cell–specific knockdown of RHOX8 resulted in male subfertility due to germ cell defects. However, this knockdown model was limited in examining the functions of Rhox8 as RHOX8 knockdown occurred only postnatally, and there was still residual RHOX8 in the testis. In this study, we generated new Rhox8 knockout (KO) mice using the CRISPR/Cas9 system. Sex determination and fetal testis development were apparently normal in mutant mice. Fertility analysis showed a low fecundity in Rhox8 KO adult males, with disrupted spermatogenic cycles, increased germ cell apoptosis, and reduced sperm count and motility. Interestingly, Rhox8 KO testes showed an increase in testis size with dilated seminiferous tubules and rete testis, which might be affected by efferent duct (ED) Rhox8 ablation dysregulating the expression of metabolism and transport genes in the EDs. Taken together, the data presented in this study suggest that Rhox8 in the Sertoli cells is not essential for sex determination and embryonic testis differentiation but has an important role in complete spermatogenesis and optimal male fertility. Summary Sentence Rhox8 knockout results in male subfertility together with a disrupted spermatogenic cycle, increased germ cell apoptosis, and reduced sperm count and motility, suggesting that Rhox8 has an important role for optimal male fertility. Graphical Abstract

The proximity and, in some instances, communication between several structures in the testis and paratestis (rete testis, epididymis, mesothelium, vestigial epithelium and paratesticular soft tissue) result in a plethora of interesting tumors and tumor-like lesions that together pose a formidable diagnostic challenge both because of their morphologic overlap and rarity. The occasional spread of tumors primarily at other sites to this region adds to the potential problem encountered. This review provides an overview of the pathology of nonmesenchymal paratesticular neoplasms and pseudotumors with a focus on the approach to tubulopapillary neoplasms for which diagnostic considerations may include carcinoma of the rete testis, malignant mesothelioma, ovarian-type epithelial tumors, epididymal carcinoma and metastatic carcinomas. The cornerstone of accurate characterization of these lesions is still a comprehensive, traditional clinicopathologic approach, clinical history (of another primary), gross examination (location) and routine light microscopy, but judicious incorporation of contemporary immunohistochemical markers may aid or in some instances be crucial in resolving the problems encountered.

Clinical staging is a critical step in the management of testicular germ cell tumors. Up to one-third of nonseminomatous germ cell tumors of the testis present with metastatic disease (clinical stages II and III). We investigated the predictors of metastatic disease at presentation in a cohort of 148 consecutive nonseminomatous germ cell tumors of the testis, over a 10-year period. The following clinical and pathologic features were evaluated: age, tumor size, dominant tumor histology, coagulative necrosis, vascular invasion, rete testis invasion and tumor extension into tunica vaginalis, hilar soft tissue, epididymis, or spermatic cord. Studied parameters were correlated with the clinical stage at presentation. Of the 148 patients with nonseminomatous germ cell tumors of the testis, 94 (63%) were clinical stage I, 26 (18%) were stage II, and 28 (19%) were stage III at presentation. Mean patient age was 31 years (range, 17–83). Mean tumor size was 4.1 cm (range, 0.6–19). On univariate analysis, the following parameters showed statistically significant association with the advanced clinical stage at presentation: vascular invasion (P<0.001), rete testis invasion (P<0.001), hilar soft tissue invasion (P<0.001), epididymis invasion (P=0.005), spermatic cord invasion (P=0.005), and coagulative necrosis (P=0.062). On multivariate analysis, only vascular invasion (P=0.011) and invasion into the rete testis and the hilar soft tissues (P=0.007 and P=0.017, respectively) demonstrated significant association with advanced clinical stage at presentation. We conclude that in addition to vascular invasion, tumor invasion into the hilum (rete testis or hilar soft tissue) is also strongly associated with metastatic disease at presentation and should be part of the routine pathology reporting.

Summary Supernumerary testis or polyorchidism is a rare congenital anomaly with about 200 reported cases in the literature. It may be associated with cryptorchidism, testicular torsion and neoplasms. Ultrasonography and magnetic resonance imaging are effective noninvasive methods of accurately detecting polyorchidism. In most cases, ultrasonography is diagnostic and magnetic resonance imaging plays confirmatory role by providing additional information if complicated with neoplasia. We report a case of 16‐year‐old man with right supernumerary testis associated with adenomatous hyperplasia of the rete testis, its sonographic and magnetic resonance imaging findings and management.

Sertoliform cystadenoma of the rete testis represents an uncommon benign tumour. They appear in patients from 26 to 62 years of age. We describe a case of a 66-year-old man with a tumour in the area of the epididymal head. The tumour markers were not increased. Under the assumption of a malignant testicular tumour an inguinal orchiectomy was performed. The cut surface of this tumour was of grey/white color and showed small cysts. The tumour consisted of two compartments. The epithelial like tumour cells showed a sertoliform growth pattern and cystic dilatations. In between the tumour cells repeatedly actin expressing sclerotic areas could be recognized as the second tumour component. Proliferative activity was not increased. Immunohistochemically the tumour cells were positiv for inhibin, S-100, and CD 99. Alpha feto protein (AFP), human chorionic gonadotropin (ß-HCG) and placental alkaline phosphatase (PLAP) as well as synaptophysin, epithelial membrane antigene (EMA), and BCL-2 were not expressed. As far as we know this is the sixth reported case of this tumour. Because of the benign nature of this tumour the correct diagnosis is important for the intra- and postoperative management. Here we present a case of this rare tumour and discuss potential differential diagnosis. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1956026143857335

Estrogens have traditionally been considered female hormones. Nevertheless, the presence of estrogen in males has been known for over 90 years. Initial studies suggested that estrogen was deleterious to male reproduction because exogenous treatments induced developmental abnormalities. However, demonstrations of estrogen synthesis in the testis and high concentrations of 17β-estradiol in rete testis fluid suggested that the female hormone might have a function in normal male reproduction. Identification of estrogen receptors and development of biological radioisotope methods to assess estradiol binding revealed that the male reproductive tract expresses estrogen receptor extensively from the neonatal period to adulthood. This indicated a role for estrogens in normal development, especially in efferent ductules, whose epithelium is the first in the male reproductive tract to express estrogen receptor during development and a site of exceedingly high expression. In the 1990s, a paradigm shift occurred in our understanding of estrogen function in the male, ushered in by knockout mousemodels where estrogen production or expression of its receptors was not present. These knockout animals revealed that estrogen's main receptor (estrogen receptor 1 [ESR1]) is essential for male fertility and development of efferent ductules, epididymis, and prostate, and that loss of only the membrane fraction of ESR1 was sufficient to induce extensive male reproductive abnormalities and infertility. This review provides perspectives on the major discoveries and developments that led to our current knowledge of estrogen's importance in the male reproductive tract and shaped our evolving concept of estrogen's physiological role in the male. Summary Sentence Estrogenic activity, which was first thought to be harmful to males, has now been shown to be produced locally in significant quantities and to be essential for male reproductive tract development and fertility.

Abstract   Tubular ectasia of rete testis (TERT) is a rarely seen benign condition of testis which can cause chronic orchalgia. TERT appears as an anechoic lesion in ultrasonography. However magnetic resonance imaging is a more sophisticated diagnostic tool. TERT is commonly associated with epididymal cysts. Generally a conservative treatment approach is preferred. In some cases surgery is required. In our case, 54-year-old male patient had bilateral TERT associated with bilateral multiple epididymal cysts. He had chronic testicular pain which did not respond to first- line conservative treatments. After use of duloxetine (60 mg PO) plus gabapentine (400 mg PO) combination as a second-line conservative treatment, the patient dramatically responded to this treatment.The patients who have chronic testicular pain caused by bilateral TERT and multiple epididymal cysts may be treated with combination of duloxetine (60 mg PO) plus gabapentine (400 mg PO) combination.   Cite this article as: Ölçücü MT, Ölçücü N, Ölçücüoğlu E, Ata Ölçücüoğlu E, Özgök Y. Response to duloxetine and gabapentin combination of a patient who has chronical orchialgia with bilateral tubular ectasia of rete testis and multiple epididymal cysts. Turk J Urol 2018; 44(3): 274-7.