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[Tumours of the undescended testis (author's transl)].

It has now been clearly demonstrated that cryptorchidism is accompanied by a very marked increase in malignancy of the ectopic testis as well as in that in place. Amongst 80 patients undergoing surgery for carcinoma of the testis 14 (17.5%) had a past history of unilateral undescended. The risk of malignancy developing in an ectopic testis is 12 to 48 times greater than that of a testis which has descended normally. It would appear that the higher the position of the testis, the greater is the risk. Orchidopexy may decreased the risk if performed before the age of 11. When the tumour is situated in an ectopic testis, the clinical picture is often misleading. When the ectopic testis has been brought down the special feature of these tumours is the frequency of spread to inguinal lymph nodes. In terms of its basic principles the treatment of these tumours does not differ from that of those affecting normal testis. The aetiology of these tumours remains uncertain. There would seem to be a consensus in favour of a disgenetic origin, possible secondary to hormonal deficiency.

Adult↗

Retinoic acid receptor alpha gene expression in the rat testis: potential role during the prophase of meiosis and in the transition from round to elongating spermatids.

Mutational studies have identified retinoic acid receptor alpha (RAR alpha) as having an essential role in spermatogenesis. The objective of this study was to determine which cells express RAR alpha within the normal rat testis by conducting in situ analyses for mRNA and protein. Characterization of RAR alpha expression revealed the time and location of the vitamin A requirement during spermatogenesis. In situ hybridization analysis of testis from adult rats showed the highest level of transcripts occurring in round spermatids at stage VIII of the spermatogenic cycle. Analysis in the developing testes revealed that the mRNA level was high from 10 to 15 days of age, both in Sertoli cells and in germ cells, and then declined in 20-day-old rats. Consistent with this, immunohistochemical studies on adult testis demonstrated that the protein was present in the nucleus of the elongating spermatids (stages IX-XI) but not in elongated spermatids. The protein was also expressed in germ cells in the prophase of meiosis and at very low levels in Sertoli cells. These results suggest a role for RAR alpha during meiosis, at the transition from round to elongating spermatids, and in Sertoli cells of developing testis.

Aging↗

[Dynamics of development of the interstitial tissue and seminiferous tubules in the testis of human fetuses].

Morphological changes in the testis of human fetuses (period of embryogenesis--from 8 to 28 weeks) during their differentiation were studied by histological and morphological methods. Investigations carried out demonstrated that complete cycle of transformation in the intestitial and embryonic tissue of the fetal testis could be divided into two main periods: the first period was attended by a gradual increase in the count and differentiation of Heydig's cells in the interstitial tissue (from the 8th to the 12th week of embryogenesis); gradual involution of Leydig's cells in the interstitial tissue and development of seminiferous tubules prevailed during the second period (from the 15th to the 28th week of embryogenesis). In the course of prenatal development of the human fetus testis Leydig's cells passed through a number of successive stages, each one being characterized by a definite functional activity level of these cells. The detected changes in the testes were apparently connected both with the changes in the Leydig's cells count and their functional activity, and with progressive growth of the tubules.

Cell Count↗

A molecular approach to sex determination in mammals.

Mammalian sex determination occurs in the gonad of the developing embryo. This process is dependent on the Y-chromosome-encoded Sry gene that acts in the somatic cells of the genital ridge. The transient nature of Sry gene expression suggests that it acts as a switch from one cell fate to another. One of the roles of Sry is to initiate the differentiation of Sertoli cells, which are the first cell type of the testis to be formed. Two genes are thought to be important in Sertoli cell differentiation and function, Sox9, an Sry-related gene, and SF-1, a nuclear hormone receptor. Sox9 is expressed in Sertoli cells throughout development of the mouse embryo, and inactivating mutations in this gene in humans give rise to XY females. SF-1 is also expressed in Sertoli cells and is thought to activate the AMH gene--an early marker of these cells. DAX-1, an X-linked member of the nuclear hormone superfamily, is a candidate for a human condition in which duplication of regions of the X chromosome results in XY females. Expression of this gene during mouse development is associated with ovary development and is down-regulated in the differentiating testis. Mutations in DAX-1 in humans have shown that this gene is not necessary for testis development. The properties of the DAX-1 gene suggest that it is important in ovary determination and might therefore be antagonistic to the action of the Sry gene.

Animals↗

Mesonephric contribution to testis differentiation in the fetal mouse.

Testes from 11.5-day-old mouse embryos, with and without attached mesonephroi, were cultured for 7 days. Isolated testes failed to develop well-differentiated testis cords: however, when cultured attached to a mesonephros from either a male or a female donor embryo, testes developed cords that were normal in appearance. Testes cultured next to a mesonephric region but separated from it by a permeable filter, did not develop normal cords, nor did testes grafted to fragments of embryonic limb or heart. When testes were grafted to mesonephric regions from mice carrying a transgenic marker, the marker was found in some of the peritubular myoid cells and other interstitial cells of the testis, but not in the Sertoli cells or the germ cells. We conclude that after 11.5 days post coitum, cells can migrate from the mesonephric region into the differentiating testis and can contribute to the interstitial cell population, and that this contribution is necessary for the establishment of normal cord structure. The germ cells in all cultured testes, whether or not differentiated cords were present, were T1 prospermatogonia: no meiotic germ cells were seen.

Animals↗

A small RNA in testis and brain: implications for male germ cell development.

BC1 RNA, a small non-coding RNA polymerase III transcript, is selectively targeted to dendritic domains of a subset of neurons in the rodent nervous system. It has been implicated in the regulation of local protein synthesis in postsynaptic microdomains. The gene encoding BC1 RNA has been suggested to be a master gene for repetitive ID elements that are found interspersed throughout rodent genomes. A prerequisite for the generation of repetitive elements through retroposition and subsequent transmission in the germline is expression of the master gene RNA in germ cells. To test this hypothesis, we have investigated expression of BC1 RNA in murine male germ cells. We report that BC1 RNA is expressed at substantial levels in a subset of male germ cells. Results from cell fractionation experiments, developmental analysis, and northern and in situ hybridization showed that the RNA was expressed in pre-meiotic spermatogonia, with particularly high amounts in syncytial ensembles of cells that are primed for synchronous spermatogenic differentiation. BC1 RNA continued to be expressed in spermatocytes, but expression levels decreased during further spermatogenic development, and low or negligible amounts of BC1 RNA were identified in round and elongating spermatids. The combined data indicate that BC1 RNA operates in groups of interconnected germ cells, including spermatogonia, where it may function in the mediation of translational control. At the same time, the identification of BC1 RNA in germ cells provides essential support for the hypothesis that repetitive ID elements in rodent genomes arose from the BC1 RNA gene through retroposition.

Animals↗

[Transformation of the rete ovarii into a rete testis and the epoophoron into an epididymis after experimental sex reversal in Gallus domesticus].

Transformation of the rete ovarii into a rete testis and of the epoophoron into an epididymis after experimental sex reversal in Gallus domesticus is described. After castration of female chicks, the medulla of the left ovary and/or the right gonadal rudiment develop into a testoid or an ovotestis. From general view, this is observed as sex reversal. In case of formation of a testoid, the epoophoron develops into an epididymis and the rete ovarii develops into a rete testis which consists of intra- and extratesticular and intracapsular parts. Thus, a luminated duct system is developed which allows the transport of semen. In case of formation of an ovotestis, the discontinuously side-by-side located parts of the rete ovarii and of the epoophoron are maintained.

Animals↗

Sox9 in testis determination.

Sox9 is an Sry-box-containing gene that encodes a transcriptional activator. During mouse gonadogenesis, Sox9 is detected in the male gonad at 11.5 days postcoitus (dpc). At 12.5 dpc, testicular cords form, morphologically distinguishing the male gonad from the ovary. From this stage onwards, Sox9 expression is restricted to the Sertoli cell lineage and persists in the adult. Humans with heterozygous mutations in SOX9 develop a skeletal syndrome known as campomelic dysplasia. Furthermore, most XY SOX9 heterozygotes show variable male-to-female sex reversal, implicating SOX9 in testis development. Sox9 heterozygous knockout mice die at birth with a syndrome similar to that of human campomelic dysplasia. In contrast to humans, XY Sox9+/- mice form normal appearing testes. Germ-line knockout of Sox9 using a conditional null allele provides a tool for generating Sox9-/- mice by simple genetic crosses. However, Sox9-/- mice die soon after 11.5 dpc because of cardiovascular defects. In vitro culture of the urogenital ridges of XY Sox9-/- results in gonads lacking testicular cords and Sertoli cell marker expression, but with the expression of ovarian-specific markers. Therefore, Sox9 is essential for diverting an intrinsically ovarian program of organogenesis toward testis formation.

Animals↗

Characterization of development-specific, cell type-specific mouse testicular antigens using testis-specific polyclonal antibodies.

Antisera were raised by immunizing rabbits with mouse testicular germ cells, and absorbed in vivo by injection into castrated male whole mice to obtain a specific antiserum which reacted with mouse germ cells. The expression of mouse testis-specific antigenic macromolecules was then studied immunochemically with the antiserum. Approximately 20 antigenic macromolecules with molecular weights ranging from 26 to 110 kD were detected in the normal adult testis. At least 12 of these were differentiation-specific antigens appearing during development of germ cells, while others were expressed in testicular germ and/or somatic cells or detected only in mature spermatozoa. This technique for raising testis-specific antisera could be useful for isolation of cDNA clones encoding their antigens, as well as for investigation of the physiological roles of these molecules in germ cell differentiation at the molecular level.

Animals↗

The testis-specific factor CTCFL cooperates with the protein methyltransferase PRMT7 in H19 imprinting control region methylation.

Expression of imprinted genes is restricted to a single parental allele as a result of epigenetic regulation-DNA methylation and histone modifications. Igf2/H19 is a reciprocally imprinted locus exhibiting paternal Igf2 and maternal H19 expression. Their expression is regulated by a paternally methylated imprinting control region (ICR) located between the two genes. Although the de novo DNA methyltransferases have been shown to be necessary for the establishment of ICR methylation, the mechanism by which they are targeted to the region remains unknown. We demonstrate that CTCFL/BORIS, a paralog of CTCF, is an ICR-binding protein expressed during embryonic male germ cell development, coinciding with the timing of ICR methylation. PRMT7, a protein arginine methyltransferase with which CTCFL interacts, is also expressed during embryonic testis development. Symmetrical dimethyl arginine 3 of histone H4, a modification catalyzed by PRMT7, accumulates in germ cells during this developmental period. This modified histone is also found enriched in both H19 ICR and Gtl2 differentially methylated region (DMR) chromatin of testis by chromatin immunoprecipitation (ChIP) analysis. In vitro studies demonstrate that CTCFL stimulates the histone-methyltransferase activity of PRMT7 via interactions with both histones and PRMT7. Finally, H19 ICR methylation is demonstrated by nuclear co-injection of expression vectors encoding CTCFL, PRMT7, and the de novo DNA methyltransferases, Dnmt3a, -b and -L, in Xenopus oocytes. These results suggest that CTCFL and PRMT7 may play a role in male germline imprinted gene methylation.

Animals↗

A tissue-specific knockout reveals that Gata1 is not essential for Sertoli cell function in the mouse.

The transcription factor Gata1 is essential for the development of erythroid cells. Consequently, Gata1 null mutants die in utero due to severe anaemia. Outside the haematopoietic system, Gata1 is only expressed in the Sertoli cells of the testis. To elucidate the function of Gata1 in the testis, we made a Sertoli cell-specific knockout of the Gata1 gene in the mouse. We deleted a normally functioning 'floxed' Gata1 gene in pre-Sertoli cells in vivo through the expression of Cre from a transgene driven by the Desert Hedgehog promoter. Surprisingly, Gata1 null testes developed to be morphologically normal, spermatogenesis was not obviously affected and expression levels of putative Gata1 target genes, and other Gata factors, were not altered. We conclude that expression of Gata1 in Sertoli cells is not essential for testis development or spermatogenesis in the mouse.

Animals↗

[Embryonal development of interstitial Leydig cells in the rat testis].

Blood testosterone concentrations are not constant throughout life, there being a direct correlation with the numbers of cells producing that hormone, for which reason the existence of two Leydig's cells populations has been proposed: one foetal formation, which disappears just prior or immediately after birth, and a subsequent adult generation. In recent studies, however, that withdrawal has not been observed. Considering all the above, we have studied the evolution of these elements during the rat foetal period. From a morphological point of view Leydig's cells do not differentiate from those in the gonadal interstice until day 17 of pregnancy, showing a considerable increase in their numbers by day 21: while from that day onwards their numbers decrease they never disappear completely. We believe those cells become differentiated from the interstitial mesenchymal cells, and that their increase is facilitated by the proliferation of these same elements.

Animals↗

[Development of peritubular myoid cells in the rat testis].

In the testes of 47 embryos, fetuses and newborn rats (Fisher strain), until the 15th day of life, the appearance and numerical dynamics of "premyoid" and myoid cells were analysed by light microscopy. The material was prepared routinely (fixed in Bouin fluid, embedded in paraffin, and cut to the thickness of 7 micrometers). The embryos of the 12th to 17th day of gestation were serially sectioned in toto, while fetal testes on the 18th to 21th day of gestation were removed and serially cut as well as the rat testes after birth. In each testis ten seminiferous tubules (cords) sectioned perpendicularly were analysed and only in two testes was it possible to find out nine but not ten perpendicularly sectioned tubules. Until the first week after birth, the lengthened cells that envelope tubules (cords) are called "premyoid". In the second half of the second week two types of lengthened cells in the envelope could be seen: one with a very thin, dark nucleus and the other with a lighter and thicker nucleus located peripherally, toward the interstitium. The former are considered myoid cells and the latter as fibroblasts. The numerical dynamics of "premyoid" and myoid cells evidently depends on the "pulsatile" effect of gondotropins. In the prenatal period, it was possible to see two increases in the number of these cells: on the 16th and on the 20th day.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Postnatal development of zinc levels in the epididymis and testis in rats under normal and experimental conditions].

Postnatal testicular and epididymal zinc concentration in the rat was investigated by means of differential pulse polarography. The zinc concentration increased gradually from birth to day 90 in the testis and up to day 60-90 in the epididymis with an abrupt increase on day 21. No marked variation in the zinc content was observed all along the epididymal duct. Experimental castration and efferent duct ligation were carried out in order to assess the influence of blood-borne and luminal androgens on epididymal zinc content. In prepubertal rats, unilateral castration and efferent duct ligation did not affect the zinc content of the epididymis. Moreover, zinc concentration was not affected by bilateral castration which induced very low plasma testosterone levels. These results suggested that epididymal zinc content did not depend upon endocrine testicular secretions, especially androgens. On the other hand, in adult rats efferent duct ligation and cryptorchidism resulted in about 50 and 70% reduction, respectively of the testicular and epididymal zinc content. A correlation was found between the absence of testicular fluid and spermatozoa or the alteration of germ cells and the decrease in epididymal and testicular zinc content.

Aging↗