RESUMEN

Reproduction in males requires the transfer of spermatozoa from testis tubules via the rete system to the efferent ductules, epididymis, and vas deferens. The rete therefore forms an essential bridging system between the testis and excurrent ducts. Yet the embryonic origin and molecular regulation of rete testis development is poorly understood. This review examines the anatomy, endocrine control, and development of the mammalian rete testis, focusing on recent findings on its molecular regulation, identifying gaps in our knowledge, and identifying areas for future research. The rete testis develops in close association with Sertoli cells of the seminiferous cords, although unique molecular markers are sparce. Most recently, modern molecular approaches such as global RNA-seq have revealed the transcriptional signature of rete cell precursors, pointing to at least a partial common origin with Sertoli cells. In the mouse, genes involved in Sertoli cell development or maintenance, such as Sox9, Wt1, Sf1, and Dmrt1, are also expressed in cells of the rete system. Rete progenitor cells also express unique markers, such as Pax8, E-cadherin, and keratin 8. These must directly or indirectly regulate the physical joining of testis tubules to the efferent duct system and confer other physiological functions of the rete. The application of technologies such as single-cell RNA-seq will clarify the origin and developmental trajectory of this essential component of the male reproductive tract.

Asunto(s)

RESUMEN

BACKGROUND: The rete testis connects seminiferous tubules of the testis with efferent ducts having a mesonephric origin. The development of the rete testis is insufficiently studied, but there is evidence suggesting that it originates from gonadal cells. Here, the formation of the rete testis was investigated from E11.5 to E16.5 using immunofluorescent staining and 3D-modeling. RESULTS: The rete testis became visible by SOX9 and PAX8 staining starting from E12.5. It was located in the mesonephros but connected with testis cords formed by Sertoli cells expressing SOX9, AMH, DMRT1. Between E13.5 and E14.5, AMH+ network of testis cords at the mesonephric side began to disintegrate in a gradient-dependent manner along the anterior-posterior axis of the gonad and connections between testis cords gradually lost AMH becoming a part of the rete. Cells combining features of Sertoli and rete cells (PAX8+ AMH+ and DMRT1+ AMH- cells) were detected starting from E14.5, suggesting that some rete cells originated from Sertoli cells. The rete ovarii, a female counterpart of the rete testis, developed in a similar way as the rete testis until E13.5. CONCLUSIONS: A part of the rete testis originates from connections between testis cords. Evidence that Sertoli cells contribute to rete cells is provided.

Asunto(s)

RESUMEN

BACKGROUND: The mechanisms by which the rete testis joins the efferent ducts, which joins the Wolffian duct during development, are not known. Mouse and chick models have been helpful in identifying genes that are important for the development of each part, but genes have not been identified as to those that play a role in the joining of each part. Clinical implications of the failure of the male reproductive tract to form a fully functional conduit for spermatozoa are not trivial. Epididymal disjunction, the failure of the efferent ducts to join the testis, is one of several epididymal anomalies that have been observed in some boys who were cryptorchid at birth. OBJECTIVE: A systematic review of studies focusing on the morphogenesis of the mesonephric duct and mesonephric tubules in different species, and identification of clinical issues should there be failure of these tissues to develop. DESIGN: PubMed and GUDMAP databases, and review of books on kidney development were searched for studies reporting on the mechanisms of morphogenesis of the kidney and epididymis. MAIN OUTCOMES MEASURE(S): Gaps in our knowledge were identified, and hypotheses coupled with suggestions for future experiments were presented. RESULTS: A total of 64 papers were identified as relevant, of which 53 were original research articles and 11 were book chapters and reviews covering morphogenesis and clinical issues. Investigators utilized multiple species including, human, mouse, chick, Xenopus, bovine, and sheep. CONCLUSION: Fundamental understanding of the morphogenesis of the male reproductive tract is limited, especially the morphogenesis of the rete testis and efferent ducts. Therefore, it is not surprising that we do not understand how each part unites to form a whole. Only one mechanism of joining of one part of the tract to another was identified: the joining of the Wolffian duct to the cloaca via controlled apoptosis.

Asunto(s)

Asunto(s)

RESUMEN

Although the histological structure of ostrich testis has been studied, very little information is currently available on the embryonic development of this organ. The aim of this study was to determine the sequence of the histological changes in diverse components of the testis in ostrich embryo from embryonic day (E) 20 to E42. The main findings were categorized into four histological features, i.e., development of sex cords, interstitial tissue and rete ducts, and the appearance of defective septa. While the lumen of sex cords, tunica albuginea, capsular rete ducts and Leydig cell precursors appeared at E26, the filum-shaped defective septa were visible at E36. The emersion of the lumen in the primary sex cords and formation of capsular rete ducts in the ostrich embryo is considerably different from that in other birds. However, tunica albuginea and Leydig cell precursors appeared in a similar pattern to those of other birds. An interesting observation was that the primordial germ cell (PGC)-like cells were completely distinct, while the capsular rete ducts were formed by trapping of some Sertoli cell aggregations in the tunica albuginea. This suggests that similar to the primary sex cords, the capsular rete ducts may originate from the Sertoli cell aggregations which had corralled some PGCs. Stereological estimations in the ostrich embryo testis showed the major proportion of testis is occupied by the seminiferous tubules, which is unlike the fowl embryo testis.

Asunto(s)

RESUMEN

Sterility due to bilateral destruction in utero or in early infancy resulting in congenital absence of the vas deferens is the rule in male patients with cystic fibrosis. To understand the developmental pattern of this anomaly, the microscopic morphology of the male excretory system was analyzed during development and the expression of the cystic fibrosis transmembrane conductance regulator protein was explored by immunohistochemistry. We observed that cystic fibrosis fetuses had no excretory ducts agenesis or obstruction until 22 weeks of gestation. However, a focal inflammatory pattern and mucinous plugs in the oldest cystic fibrosis case suggested a disruptive mechanism. Immunolabeling of cytoplasmic epithelial cystic fibrosis transmembrane conductance regulator protein was demonstrated in all cystic fibrosis and control cases with a similar pattern of expression of the protein between age-matched controls and cystic fibrosis cases. At midgestation, an apical intensification appeared in both cystic fibrosis and control cases and was stable during the remainder of fetal life. No gradient of intensity could be detected between the different segments of the excretory tract. These findings are different from those reported in adults. The absence of any morphologic anomaly until 22 weeks of gestation, the focal destruction of the epithelial structures during the second trimester, and the chronological pattern of expression of cystic fibrosis transmembrane conductance regulator are of interest for a better understanding of the pathophysiology of this disease.

Asunto(s)

RESUMEN

Testis cords are specialized tubes essential for generation and export of sperm, yet the mechanisms directing their formation, and the regulation of their position, size, shape, and number remain unclear. Here, we use a novel fluorescence-based three-dimensional modeling approach to show that cords initially form as a network of irregular cell clusters that are subsequently remodeled to form regular parallel loops, joined by a flattened plexus at the mesonephric side. Variation in cord number and structure demonstrates that cord specification is not stereotypic, although cord alignment and diameter becomes relatively consistent, implicating compensatory growth mechanisms. Branched, fused, and internalized cords were commonly observed. We conclude that the tubule-like structure of testis cords arise through a novel form of morphogenesis consisting of coalescence, partitioning, and remodeling. The methods we describe are applicable to investigating defects in testis cord development in mouse models, and more broadly, studying morphogenesis of other tissues.

Asunto(s)

RESUMEN

Lunatic fringe belongs to a family of beta1-3 N-acetyltransferases that modulate the affinity of the Notch receptors for their ligands through the elongation of O-fucose moieties on their extracellular domain. A role for Notch signaling in vertebrate fertility has been predicted by the intricate expression of the Notch receptors and their ligands in the oocyte and granulosa cells of the ovary and the spermatozoa and Sertoli cells of the testis. It has been demonstrated that disruption of Notch signaling by inactivation of lunatic fringe led to infertility associated with pleiotropic defects in follicle development and meiotic maturation of oocytes. Lunatic fringe null males were found to be subfertile. Here, we report that gene expression data demonstrate that fringe and Notch signaling genes are expressed in the developing testis and the intratesticular ductal tract, predicting roles for this pathway during embryonic gonadogenesis and spermatogenesis. Spermatogenesis was not impaired in the majority of the lunatic fringe null males; however, spermatozoa were unilaterally absent in the epididymis of many mice. Histological and immunohistochemical analysis of these testes revealed the development of unilateral cystic dilation of the rete testis. Tracer dye experiments confirm a block in the connection between the rete testis and the efferent ducts. Further, the dye studies demonstrated that many lunatic fringe mutant males had partial blocks of the connection between the rete testis and the efferent ducts bilaterally.

Asunto(s)

RESUMEN

The rete testis is formed in the fifth week of intra-uterine life. The epithelium along the medial side of the mesonephric ridge thickens to form a genital ridge; cellular gonadal cords at the periphery of the ridge unite with a tubular network from the mesonephric mesenchyme forming the testicular rete. On ultrasound, a range of normal appearances of the rete testis is recognised from ill-defined areas of decreased reflectivity to a coarse tubular appearance (often with finger like projections). In the present review the embryological development of the rete testis is briefly outlined. In addition, the important anatomical variations, pertinent to ultrasound imaging, will be presented.

Asunto(s)

RESUMEN

The ultrastructure of the developing extratesticular rete testis, the efferent ductules and the establishment of the urogenital junction were studied in bovine embryos and fetuses of 41 through 95 days post conceptionem. The efferent ductules originate as a new set of secondary mesonephric tubules from the dorsal aspect of the nephric giant corpuscle and grow in the direction of the Wolffian duct. Cytological differentiation of the efferent ductules proceeds in a proximo--distal direction. At about 50-60 days, the simple columnar epithelium of the proximal portions of the efferent ductules already consists of the two typical cell types, i.e. reabsorptive principal cells with an endocytotic apparatus and a brush-border and ciliated cells. The lumen of the proximal portion is temporarily filled with intraductular blood vessels and perivascular tissue which may represent vestigial rudiments of glomeruli associated with the efferent ductules. At 50 to 60 days, the extratesticular rete still has a blastema--like appearance and consists of irregular cells with abundant glycogen. Extensions of the extratesticular rete come into contact with the efferent ductules and create the first end-to-side anastomoses with the latter. Somewhat later, the separating basal laminas vanish and invading rete cells intermingle with the epithelium of the efferent ductules, thus establishing the urogenital junction.

Asunto(s)

RESUMEN

The development of the intragonadal rete testis and the establishment of the connection between seminiferous and straight testicular tubules was studied using ultrastructural and histochemical methods in 60 bovine embryos and fetuses ranging from day 39 through day 225 post conceptionem. The methodology included a modified acetylcholinesterase (AChE) reaction as a selective marker for pre-Sertoli cells and a modified microsomal aminopeptidase (MAP) reaction as a selective marker for the epithelia of rete testis and straight testicular tubules. Between 40 and 45 days, the rete testis is predominantly an extratesticular rete situated in the cranial peduncle of the gonadal fold and in broad contact with the pro/mesonephric giant corpuscle. During this period, the intragonadal rete enters the gonad proper from its craniodorsal pole and extends into the cranial fourth of the testis. Between 60 and 110 days the rete testis attains its definitive position, extending into the central longitudinal axis as far as to the caudal fourth of the testis. For the caudal expansion of the rete testis the preceding proliferation of the mediastinal stroma is an important prerequisite. In the 40 to 45-day-old embryo the area of the testicular cords may be divided into two zones. A narrow outer zone contains plate-like cords with a thick diameter, and a larger central zone is filled with a network of thinner cords. Only the thick outer cords transform into the permanent seminiferous tubules, whereas the thinner cords in the central zone are transitory structures that disappear between 45 and 110 days. One important function of these transitory cords is to establish a continuous system of basal laminae that allows a direct connection between the central ends of the growing seminiferous tubules and the peripheral extensions of the rete testis (future straight testicular tubules). The first true straight testicular tubules become visible between 85 and 110 days. Due to a strong proliferation of the tubulus rectus-cells the straight testicular tubules elongate continuously, and the border between the rete system and the seminiferous tubules is slowly shifted towards the testicular periphery. This shift is not restricted to the prenatal period, but proceeds until after birth. At the cytological level, the formation and elongation of the straight testicular tubules is effected by proliferating cells that advance along the continuous basal lamina into the area of the seminiferous tubules. The pre-Sertoli and germ cells in this zone of invasion are separated from each other and overgrown by the tubulus rectus-cells. Exposed to the special milieu of the straight testicular tubules, pre-Sertoli and germ cells apparently cannot survive and finally disappear.

Asunto(s)

RESUMEN

The sites of action and the physiological role of oestrogens in the male reproductive tract are poorly understood. We have undertaken a systematic study of the immunoexpression of oestrogen receptor-alpha (ER alpha) in the male rat from late fetal life through to adulthood and compared the findings with results obtained in the marmoset monkey (Callithrix jacchus) from neonatal to adult life. The testes, rete testis, efferent ducts and epididymis were examined from normal male rats (aged 4, 8, 10, 15, 20, 25, 38, 48 and 90 days) and from male rat fetuses on days 17.5 and 18.5 of gestation; comparable tissues were examined from neonatal, infantile, peripubertal and adult marmosets aged 8, 18-24, 54-62 and 92-112 weeks respectively. Immunolocalisation of ER alpha used antigen retrieval and a monoclonal antibody directed to the N-terminus, which had proved superior to six other antisera tested. ER alpha was immunoexpressed in interstitial cells, including the fetal/ neonatal generation of Leydig cells, in both the rat and marmoset. In the rat, the adult generation of Leydig cells were also immunopositive for ER alpha whereas the comparable cells in the marmoset were only weakly immunopositive. ER alpha was not expressed in Sertoli cells, peritubular myoid cells, blood vessels or germ cells at any time in either species. In late fetal life in the rat, ER alpha was immunoexpressed in cells surrounding the mesonephric tubules, whereas postnatally it was expressed in the epithelium of the rete testis and efferent ducts at all ages from 4 to 90 days; this immunoexpression was most pronounced in the efferent ducts. In the marmoset, the efferent ducts, but not the rete testis, also showed intense immunoexpression of ER alpha. Apart from sporadic immunostaining for ER alpha in the epididymal duct of the rat in the neonatal period, the caput, corpus and cauda epididymis were negative for immunoexpression of ER alpha at all ages in both species. These findings suggest that the main actions of oestrogens in the male reproductive tract, mediated by ER alpha, are related to the development and function of the efferent ducts and the Leydig cells. In consideration of data from this and previous studies of oestrogen binding, we predict possible sites of expression of other oestrogen receptors (e.g. ER beta) in Sertoli cells and the epididymis. Interactive effects, related to the relative levels of androgens and oestrogens, could be physiologically important in the excurrent ducts of the adult testis.

Asunto(s)

RESUMEN

In 11 testes of different developmental stages (from 10-week-old embryos to adult) the cytokeratin and vimentin expression patterns of rete testis and epididymis were investigated immunohistochemically in formaldehyde-fixed paraffin-embedded material. In addition, immunofluorescence microscopy including double immunofluorescence was performed on frozen sections of 3 of these 11 cases. Rete testis and epididymis cells displayed a heterogeneous co-expression of cytokeratin and vimentin. In double immunohistochemistry, differences in distribution of keratin and vimentin intermediate filaments with predominance of cytokeratins in the apical cytoplasmic regions and of vimentin filaments in the basal portions of the cells were found. Cytokeratin expression preceded the appearance of vimentin: cytokeratin was already detectable in 10-week-old embryos, while weak vimentin immunoreactivity was first seen in 12-week-old embryos and became conspicuous in testes around the perinatal period. In testes of children up to 2 years of age the cytoplasmic distribution of cytokeratin and vimentin was more homogeneous. Predominance of the basal cell portions for vimentin and the apical regions for cytokeratin staining were less pronounced than in adult testes. In the proximal and distal parts of the epididymis a different intermediate filament expression pattern was found with a clear predominance of cytokeratin near the rete.

Asunto(s)

RESUMEN

Transitions from the rete testis into the ductuli efferentes and from the ductuli efferentes into the ductus epididymidis were examined in the epididymes of 4 patients with prostatic cancer aged 65, 72, 77 and 78 years, in the epididymis of a 19 year-old accident victim and in the epididymis of an embryo of the 12th week. Concerning the former area, the results published up to now were confirmed. But according to our examinations, the transition from the ductuli efferentes into the ductus epididymidis is different from what has been described in the literature so far. In the adult human, the ductuli efferentes do not show end-to-side connections with the ductus epididymidis, but end-to-end junctions with "extensions" of the ductus epididymidis which finally join the ductus epididymidis end-to-side. However, in the epididymis of the embryo, one still finds end-to-side connections of ductuli efferentes and the ductus epididymidis. It was concluded that the extensions of the ductus epididymidis are formed during the development of the system of canaliculi in the epididymis from the embryonal stage to adult age.

Asunto(s)

RESUMEN

The development of rete testis in the rat, rabbit and guinea pig foetuses has been studied, as well as the influence of prolactin and thyrotropin on differentiation of its cells. It was shown that the rete testis tubules, as well as the seminiferous tubules develop from sex cords, which were derived from coelomic epithelium cells and gonocytes. The development of seminiferous tubules and rete testis was described at various stages of prenatal ontogenesis. Thyrotropin and prolactin exert different effects on differentiation of the rete testis cells: the former increases the mitotic activity of gonocytes and the latter increases that of epithelial cells and enhances degenerative processes in primary germ cells.

Asunto(s)

RESUMEN

The epididymis of ratitae is subdivided into a main part and a appendix epididymidis. The appendix epididymidis consists of the ductus aberrans and ductuli aberrantes. The ductus aberrans is the cranial continuation of the ductus epididymidis. The appendix epididymidis is cranially attached to the adrenal gland. In the main part of the epididymis the largest part of the rete testis is found. The rete testis is composed of an intratesticular rete (also named tubuli recti), and intracapsular rete (with a longitudinal cistern and a true rete), and an extratesticular rete (predominantly consisting of approximately 20 longitudinal channels). The rete testis develops most likely embryonally from buds of the glomerular capsules of the mesonephros. The ductuli efferentes proximales also from these capsules, while the ductuli efferentes distales develop from the proximal and distal tubules and intermediate-segments of the mesonephros. The ductus epididymidis originates from the Wolffian duct and meanders dorsolaterally through the epididymis.

Asunto(s)

Asunto(s)