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PubMedDate not supplied

Human testicular development and the role of the mesonephros in the origin of a dual Sertoli cell system.

Some aspects of the development of the human testis (and overy) are discussed and the main theories regarding gonadal differentiation summarized. The major part of this review deals with the origin and differentiation of the three groups of somatic cellular content: Sertoli cells, Leydig cells and peritubular cells. The most important role of the mesonephros in gonadal development is described. Under the influence of the mesonephros, a second type of meiosis-inducing Sertoli cell differentiates and becomes the opponent of a meiosis-preventing type of Sertoli cell which derives from the coelomic epithelium. All somatic cells are pooled in the central gonadal blastema which is part of the medulla. They migrate via the rete blastema to the sites of their final differentiation. Included are the precursors of the Leydig cells and the peritubular cells.

Cell Differentiation↗
PubMed1996

Effects of selenium deficiency on testicular morphology and function in rats.

For four generations rats were fed a low selenium diet (2-7 micrograms Se kg-1) or the same diet with 250 or 300 micrograms Se kg-1 added as selenite. In male rats of the first generation that had been fed the diets from the age of 20 days onwards, selenium depletion led to slightly delayed testis growth during pubertal development that was compensated for in the later stages of maturation. In adult rats fed the low selenium diet for nearly a year no changes in testicular mass and morphology were observed. The serum concentration of testosterone of 6-month-old, selenium-depleted animals was, however, slightly lower than that of adequately supplied controls, and the stimulation of testosterone secretion by administration of GnRH or LH resulted in a significantly less marked rise in the serum concentration of testosterone. From the second generation onwards the testis mass, expressed as a percentage of the body mass, decreased and in the fourth generation was less than 50% of that of the controls. The male gonads of fourth generation animals showed a severe bilateral atrophy, in which the seminiferous tubules were considerably reduced in diameter and almost entirely lined by Sertoli cells and a few stem cells. Differentiated spermatozoa could not be detected. The alterations were reversible and spermatogenesis was restored by feeding the selenium-adequate diet. The findings indicate that testicular morphology and functions are affected by severe selenium deficiency and that the element is necessary for testosterone biosynthesis and the formation and normal development of spermatozoa.

Animals↗
PubMed1976

Comparative cytomorphologic aspects of the male germ cells, especially of the "Gonia".

During early development of the human testis the male germ cell first appears as primordial germ cell or gonocyte and enters the prospermatogonial stage after the twelfth week of gestation. Prospermatogonia lack glycogen particles and are connected by intercellular bridges. During the same period in the ovary the female germ cell undergoes its oogonial stage. Prospermatogonial and oogonial development have been studied histologically in three laboratory species (white mouse, Acomys caharhinus dimidiatus. golden hamster). According to the therminolgy of Hilscher et al. (1974) proposed for the rat, prospermatogonia have to be subdivided into M- T (1)- and T (2)-prospermatogonia. In the ovary they correspond to oogonia, oocytes in the prophase of meiosis and oocytes in the diplotene stage.

Adult↗
PubMed1989

A 14 bp promoter element directs the testis specificity of the Drosophila beta 2 tubulin gene.

To analyze the regulation of gene expression during male germ cell development, we investigated the testis-specific expression of the Drosophila beta 2 tubulin gene. Germ line transformation experiments with the upstream region of the D.melanogaster beta 2 tubulin gene fused to the Escherichia coli lacZ gene resulted in the correct tissue specific expression of the reporter gene. Furthermore, we showed that the upstream sequences of the beta 2 tubulin gene of the distantly related species D.hydei can drive the expression of the lacZ gene testis specifically in D.melanogaster flies. A detailed deletion analysis showed that 53 bp of upstream and 23 bp (D.melanogaster) or 29 bp (D.hydei) of leader sequences are sufficient to confer tissue specificity. The short promoter regions contain a 14 bp motif at identical positions in both species, which acts as a position-dependent promoter element. In vitro mutagenesis and subsequent germline transformation experiments revealed that this sequence is the only element necessary for the testis-specific transcription of the beta 2 tubulin gene in Drosophila.

Animals↗
PubMed1989

Messenger ribonucleic acid encoding an apparent isoform of phosphorylase kinase catalytic subunit is abundant in the adult testis.

The complete amino acid sequence for a novel member of the protein kinase family was deduced from the nucleotide sequence of a cloned human cDNA. This putative protein kinase, given the preliminary designation "PSK-C3," is similar in primary structure to phosphorylase kinase catalytic subunit (PhK-gamma) isolated from rabbit skeletal muscle. The level of similarity does not appear sufficient, however, to suggest that PSK-C3 represents the human homolog of skeletal muscle PhK-gamma. Rather, it seems likely that PSK-C3 is a novel PhK-gamma isoform. From a cross-species Northern hybridization experiment using adult rat tissue RNA, a transcript homologous to PSK-C3 was found to be abundant in the testis but could not be detected in any of 12 other tissues tested, including skeletal muscle, liver, and ovary. Increasing levels of PSK-C3 mRNA in the testis correlate with postnatal testicular development, suggesting possible hormonal regulation of gene transcription. Energy released by glycogeneolysis in the testis may help fuel the process of spermatogenesis.

Amino Acid Sequence↗
PubMed1992

Influence of chick or quail embryonic testes on the reproductive system of the quail embryo.

The reproductive system of female quail embryo undergoes masculinization under the influence of chick and quail embryonic testis grafted into an extraembryonic coelom. Müllerian ducts undergo regression. The left gonad transforms into an ovotestis and the right gonad either does not develop or transforms into a small testis. Testicular chick or quail graft does not affect the development of the cortical ovarian-like region in the left testis of male hosts. In some quail testicular grafts developing in female quail hosts cortical region is retained longer than normally.

Animals↗
PubMed1994

Proenkephalin gene expression in testicular interstitial cells is down-regulated coincident with the appearance of pachytene spermatocytes.

Two distinct forms of proenkephalin messenger RNA (mRNA) are present in the murine testis, a family of 1.7 kilobases (kb), germ cell-specific transcripts and a 1.45-kb form that is also found in somatic tissues. In situ hybridization and molecular analysis of purified spermatogenic cell types were used to characterize the cellular localization of these different transcripts during development of the mouse testis. Both forms of proenkephalin mRNA were observed in isolated germ cells by RNA gel-blot analysis, but in distinct developmental patterns; the 1.7-kb transcripts were present in cells undergoing meiosis and spermiogenesis, whereas the 1.45-kb mRNA was detected primarily in type B spermatogonia. In contrast, in situ hybridization analysis did not detect significant amounts of the 1.45-kb transcript in any spermatogenic cell type. Using transcript-specific probes, distinct patterns of developmental expression were evident for the two mRNAs. The 1.45-kb transcript was the only form detected in the prepubertal testis, where it was localized mainly in interstitial cells. In contrast, the 1.7-kb transcripts were the major mRNAs observed in the adult testis and were localized to spermatogenic cells. A transition from the prepubertal to the adult pattern occurred on or about postnatal day 21, when proenkephalin-expressing pachytene spermatocytes begin to populate the seminiferous tubules. In situ hybridization analysis further demonstrated that proenkephalin gene expression in mutant (at/at) mice, which lack germ cells, was identical to that observed in the early prepubertal testis. These results suggest that the 1.45-kb proenkephalin mRNA is developmentally down-regulated in mouse interstitial cells and that this process requires ongoing spermatogenesis.

Animals↗
PubMed1997

Function and regulation of heat shock factor 2 during mouse embryogenesis.

The spontaneous expression of heat shock genes during development is well documented in many animal species, but the mechanisms responsible for this developmental regulation are only poorly understood. In vertebrates, additional heat shock transcription factors, distinct from the heat shock factor 1 (HSF1) involved in the stress response, were suggested to be involved in this developmental control. In particular, the mouse HSF2 has been found to be active in testis and during preimplantation development. However, the role of HSF2 and its mechanism of activation have remained elusive due to the paucity of data on its expression during development. In this study, we have examined HSF2 expression during the postimplantation phase of mouse development. Our data show a developmental regulation of HSF2, which is expressed at least until 15.5 days of embryogenesis. It becomes restricted to the central nervous system during the second half of gestation. It is expressed in the ventricular layer of the neural tube which contains mitotically active cells but not in postmitotic neurons. Parallel results were obtained for mRNA, protein, and activity levels, demonstrating that the main level of control was transcriptional. The detailed analysis of the activity of a luciferase reporter gene under the control of the hsp70.1 promoter, as well as the description of the protein expression patterns of the major heat shock proteins in the central nervous system, show that HSF2 and heat shock protein expression domains do not coincide. This result suggests that HFS2 might be involved in other regulatory developmental pathways and paves the way to new functional approaches.

Animals↗
PubMed1991

High-resolution scanning electron micrographs of freeze-cracked cells in testes from normal and irradiated rats at different stages of gonadal development.

Newly developed techniques in high-resolution scanning electron microscopy (SEM) and for tissue-processing procedures have been applied to an investigation of structures of various cells in rat testes at different stages of gonadal maturation. A series of high-resolution SEM micrographs are presented which survey the surfaces of different types of testis cells during normal development, and which also illustrate ultrastructural features of some of their intracellular organelles. In addition, a series of high-resolution SEM micrographs are presented which compare the structural features of Sertoli cells in normal testes with those in germ-cell-depleted testes obtained from rats killed at varying times after having been irradiated in utero. We describe our observations on the structural properties of surfaces and intracellular organelles in Sertoli cells, Leydig cells, peritubular myoid cells, and some classes of germinal cells. We also consider the possible role of Sertoli cell apical cytoplasmic processes in lumen formation. Similarities are pointed out between the structure of germ-cell-depleted testes, resulting from irradiation in utero, and the structure of germ-cell-depleted testes in seasonal breeders during periods of involution. Finally, we discuss advantages and disadvantages of methods employed to reveal the fine structure of intracellular organelles in cells of the testis.

Animals↗
PubMed2000

Localization of cytochrome P450 aromatase and estrogen receptors alpha and beta in testicular cells--an immunohistochemical study of the bank vole.

Age- and light-dark cycle-induced changes in immunoexpression of aromatase and estrogen receptors alpha and beta were studied in testes of a seasonally breeding rodent, the bank vole. Seasonal breeding can be mimicked by exposure to different light cycle regimes. In testes of animals that were exposed to long light cycles of 18 h light and 6 h darkness aromatase was in Leydig cells and seminiferous tubules, mainly in spermatocytes, whereas in animals exposed to short light cycles (6 h light and 18 h darkness), only Leydig cells exhibited positive immunostaining for aromatase. Whatever the age of animals, immunostaining for estrogen receptor alpha was restricted to Leydig cells, whereas estrogen receptor beta immunoreactivity was mainly confined to Sertoli cells of both of immature and adult animals, independently of the regimes of light. Additionally, in testes of animals that were exposed to long light cycles, estrogen receptor beta immunoreactivity was observed in seminiferous tubules. Nuclei of germ cells, predominantly spermatocytes and elongated spermatids, were strongly positive which correlated well with aromatase immunoreactivity. As far as we know, the present study is the first study that describes immunoexpression of aromatase and both estrogen receptors alpha and beta in testis of the bank vole. We provide strong evidence that estrogens are not only produced in Leydig cells but also in germ cells in this rodent. These female hormones may play a physiological role in testis, likely in the development of germ cells during spermatogenesis.

Aging↗
PubMed2002

Seminoma arising in cryptorchid testis 25 years after orchiopexy: case report.

A 33-year-old man who underwent right orchiopexy at age 8 for undescended testis had a swelling develop at the same site 25 years later. He underwent right high orchiectomy. Histopathologic examination of the resected specimen suggested seminoma, and he was treated with chemotherapy (cisplatinum, etoposide, and bleomycin.) Even though the ideal age at orchiopexy is unknown, early intervention is advocated to preserve fertility and prevent malignant transformation. The management of cryptorchid testis is controversial. In view of the persistent malignant potential of this condition, early orchiopexy and lifelong follow-up are recommended.

Adult↗
PubMed2002

Relapsed plasma cell leukaemia presenting with aggressive extramedullary plasmacytomas in the meninges and testis--a missed opportunity for induction CNS prophylaxis.

After initial treatment, a 54-year-old male with plasma cell leukaemia developed extramedullary relapse in the testis and meninges without evidence of bone marrow involvement. We postulate that the central nervous system (CNS) and testis may have served as sanctuary sites for the disease during initial treatment. A role for CNS prophylaxis in plasma cell leukaemia is suggested.

Humans↗
PubMed1998

CD99, keratin, and vimentin staining of sex cord-stromal tumors, normal ovary, and testis.

CD99, a marker for MIC-2, reacts with normal Sertoli cells and granulosa cells. We investigated CD99 expression in the development of normal ovary and testis as well as in 25 sex cord-stromal tumors (SCSTs), 7 epithelial neoplasms, and 6 germ cell tumors. Normal Sertoli cells and mature granulosa cells showed 3+ staining with CD99. Pregranulosa cells of primordial follicles were negative. All of the eight Sertoli-Leydig cell tumors were positive with antibody to CD99, with the well-differentiated tumors showing the greatest degree of staining intensity. Reactivity of 2+ to 3+ with CD99 was observed in all of the 11 granulosa cell tumors and in yolk sac components of the germ cell tumors investigated. All of the poorly differentiated carcinomas were negative with CD99. We concluded that CD99 might be a useful marker for SCSTs and that its degree of reactivity correlates with the degree of differentiation in Sertoli-Leydig cell tumors. Additionally, CD99 might aid in distinguishing granulosa cell tumors of the ovary from poorly differentiated carcinomas.

12E7 Antigen↗
PubMed1978

Genetic variation, cellular distribution and ontogeny of sorbitol dehydrogenase and alcohol dehydrogenase isozymes in male reproductive tissues of the mouse.

Cellulose acetate zymograms of alcohol dehydrogenase (ADH) and sorbitol dehydrogenase (SDH) extracted from male reproductive tissues of inbred mice were examined. ADH isozymes were differentially distributed in these tissues of C3H/He mice; ADH-B2 was observed in all tissues and testis cellular preparations examined; ADH-C2 was localized predominantly in the epididymis but was also present in the seminal vesicles, coagulating gland, and prostate gland. SDH was broadly distributed in these tissues but exhibited highest activities in the seminal vesicles, coagulating glands, and germinal cells of mature testes. Genetic variants for ADH-C2 and SDH provided evidence for (1) the identity of a second form of SDH in epididymis with ADH-C2; (2) the genetic identity of kidney, seminal vesicle, and testis SDH; and (3) the gentic identity of stomach and epididymal ADH-C2. Developmental changes in testis and epididymal ADH isozymes during maturation were examined. ADH-C2 appeared in the mature epididymis whereas ADH-B2 exhibited no major changes in activity in testis and epididymis during development.

Alcohol Oxidoreductases↗
PubMed1997

A single-centre observational study of surgery and late malignant events after chemotherapy for germ cell cancer.

OBJECTIVE: To review the impact of surgical staging after treatment on the late malignant events in an unselected group of patients treated with chemotherapy for germ cell cancer of the testis over the last 16 years. PATIENTS AND METHODS: The study comprised 256 patients treated between 1978 and 1994 who were reviewed for late relapse and development of second germ cell and non-germ cell cancer. RESULTS: At diagnosis, 142 patients had clinical stage 2, 30 stage 3 and 84 stage 4 disease; 57 patients relapsed within 20 months of treatment, while late germ-cell cancer relapses (> or = 24 months after treatment) occurred in six patients. Of patients relapsing early or late, 42% and 33%, respectively, received surgery after treatment. Only two of those relapsing late remain progression-free with further treatment. Four patients developed germ cell cancer in the contralateral testis, while six developed second non-germ cell cancers. CONCLUSION: Late events occurred in 6.2% of 256 patients in this series, from 29 to 141 months after treatment. Given that the late relapse rate of six of 256 (2.3%) is less than the incidence of mature teratoma at routine retroperitoneal lymph node dissection, more patients may eventually relapse. These results suggest that there might be a case to evaluate the use of ultrasonographic surveillance of the retroperitoneum and testis at 5, 10 and 20 years, in addition to extending routine surveillance.

Adult↗
PubMed1994

Human testis cDNAs identified by sera from infertile patients: a molecular biological approach to immunocontraceptive development.

Sera from patients with known or suspected immunological infertility were used to screen a human testis cDNA library. A total of 59 sera detected 38 unique cDNA inserts of which four were testis specific by Northern blot analyses. One of these is a testis-specific isoform of calpastatin. Five additional clones, although not testis specific, were found to be testis abundant. The number and type of clones identified by these human sera suggests a possible aetiology for immunologic infertility. The testis-specific clones will be further characterized to establish their usefulness as contraceptive vaccine candidates.

Antigens↗
PubMedDate not supplied

Expression of heat shock proteins in developing and degenerating rat testes.

In the testis, several types of heat shock proteins (HSPs) have been identified and characterized, although the cellular basis of the HSPs remains elusive. In the present study, alterations in the cellular localization of HSPs, including HSP 25, 60, 70, and 90, were studied during the developing and degenerating periods in the rat testis using immunohistochemistry and Western blotting. HSP25 was expressed in neither germ cells nor somatic cells on all days examined. In contrast, HSP 60 was expressed in Leydig cells during neonatal and prepuberty periods, and only in spermatogonia and primary spermatocytes after puberty. HSPs 70 and 90 were expressed in germ cells, Sertoli cells, and Leydig cells during neonatal and early developing testes, and in spermatocytes and round spermatids after puberty. Besides, there was faint expression of HSP 90 protein in spermatogonia in this period. In the degenerative condition, all HSP proteins were markedly expressed in germ cells after surgery. It would appear that HSPs play roles in unique homeostasis in testes.

Animals↗
PubMedDate not supplied

Mesotheliomas of tunica vaginalis testis of Fischer 344 (F344) rats treated with acrylamide: a light and electron microscopy study.

The incidence of spontaneous mesotheliomas of the tunica vaginalis testis, documented to be 1.3% in Fischer 344 rats can be increased by long term exposure to acrylamide. The light microscopic and electron microscopic features of tumors developing spontaneously in control animals were compared with those that developed in acrylamide treated animals to determine whether the tumors in the experimental group have any distinctive characteristics. The experimental group comprised three subgroups, i.e. animals exposed to acrylamide in three doses 0.1, 0.5 or 2.0 mg/kg/day over a period of 104 weeks. A total of 35 tumors were examined--7 in control group, 9 in low-dose group, 8 in mid-dose group and 11 in the high-dose group. Most tumors measured less than 1 cm in diameter in aggregate and approximately one-third of all tumors were of microscopic size, less than 5 mm in diameter. All tumors were classified as epithelial mesotheliomas. Three distinct microscopic patterns were recognized (papillary, tubular or solid). All tumors had papillary features, and focally showed some tubular or solid components. No ultrastructural differences were found between tumors of the four groups of animals. It was concluded that the tumors that developed in the tunica vaginalis testis of acrylamide treated animals do not differ morphologically from those that developed spontaneously in control animals. Cellular uniformity, small size of lesions and the absence of perotoneal seeding and metastasis suggests that the mesotheliomas of tunica vaginalis testis of Fischer 344 rats in this study were benign and equivalent to human benign mesothelioma of tunica vaginalis testis or adenomatoid tumors.

Acrylamide↗