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PubMed1989

Simple cyst of the testis.

We report 5 cases of simple cyst of the testis, the largest series to date, and review the literature. Included are 2 autopsy cases, a case of a multilocular simple cyst and 1 case treated nonoperatively. Based on our experience, simple cyst of the testis should be suspected particularly in an enlarged but otherwise palpably normal testis. High resolution real-time scrotal sonography revealing an anechoic mass in the testis with well defined walls, and enhanced posterior through transmission and edge shadowing is diagnostic for a simple cyst. An asymptomatic simple cyst of the testis may be treated with observation alone. The symptomatic simple cyst should be treated ideally with local parenchyma-sparing excision.

Aged↗
PubMed1988

Replantation of the testis: report of a case.

To our knowledge there has been no report to date of successful testis replantation after complete traumatic severance of the funiculus within the scrotum. We report a case in which both funiculi were cut completely (one of which was severed 0.8 cm. proximal to the upper pole of the testis, and the other just at the junction of the funiculus and the testis). We successfully rejoined the testis with the funicular stump to the proximal cut end of the right side using a microsurgical technique. The total ischemia period of the replanted testis was 6 hours. The penis was erect 4 days postoperatively and blood testosterone level was within the normal range. At testicular biopsy 120 days postoperatively the germ cells could be seen in various stages of development and the appearance of the Leydig cells was normal.

Adult↗
PubMed2000

Differential regulation of the oxidative 11beta-hydroxysteroid dehydrogenase activity in testis and liver.

11Beta-hydroxysteroid dehydrogenase (11beta-HSD) Type I enzyme is found in testis and liver. In Leydig cell cultures, 11beta-HSD activity is reported to be primarily oxidative while another report concluded that is primarily reductive. Hepatic 11beta-HSD preferentially catalyzes reduction and the reaction direction is unaffected by the external factors. Recent analysis of testicular 11beta-HSD revealed two kinetically distinct components. In the present study, various steroid hormones or glycyrrhizic acid (GCA), given for 1 week, or thyroxine given for 5 weeks to normal intact rats had different effects on the 11beta-HSD oxidative activity in testis and liver. Deoxycorticosterone, dexamethasone, progesterone, thyroxine, and clomiphene citrate increased testicular 11beta-HSD oxidative activity, but decreased hepatic enzyme activity except for deoxycorticosterone (unchanged). Corticosterone and testosterone decreased 11beta-HSD oxidative activity in testis but not that of liver (which was unchanged). Estradiol, GCA and adrenalectomy lowered oxidative activity of 11beta-HSD in testis and liver, but the degrees of reduction were different. The in vivo effects of glucocorticoids too were different, even in the same organ. Dexamethasone, a pure glucocorticoid, has greater affinity for glucocorticoid receptors (GR) than corticosterone. The direct effects of dexamethasone via GR in increasing testicular 11beta-HSD oxidative activity may override its indirect effects. Possibly, the reverse occurs with corticosterone treatment, as it has both glucocorticoid and mineralocorticoid effects. Because both organs have Type I isoenzyme, the difference in 11beta-HSD oxidative activities of these two organs could be attributable to the presence of an additional isozyme in testis or differences in tissue-specific regulatory mechanisms.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2002

Evaluation and management of ectopic penile testis.

Ectopic testes are found in the superficial inguinal scrotum, base of penis, perineum, or medial thigh. In cases in which the testis crosses the midline, the cord structures may cross intra-abdominally or after exiting the inguinal canal. We describe a patient with an ectopic testis located on the penile shaft ipsilateral to a scrotal testis. Diagnostic laparoscopy identified the cord structures exiting opposite the testis. A scrotal location was achieved using a single high scrotal incision. This case illustrates the utility of laparoscopy for the evaluation and management of a testis that crosses the midline.

Adolescent↗
PubMed2002

Corticosterone administration to rat pups, but not maternal separation, affects sexual maturation and glucocorticoid receptor immunoreactivity in the testis.

Prenatal stress strongly affects sexual dimorphism of male rats. Much less information is instead available on the effects of postnatal stress on sexual maturation during the so-called stress hyporesponsive period (SHRP). For this reason, we compared corticosterone-treated (CS; 10 mg/kg sc, suspended in sesame oil) or maternally separated pups (MS; 5 h/day in the first week of life) with control rats. Control and MS pups also received sesame oil injections. The effects of these procedures on physical development (body weight and eye opening), sexual maturation [anogenital distance, testis weight, 3beta-hydroxysteroid dehydrogenase/(Delta5-4) (3betaHSD) isomerase activity and time to testis descent] and glucocorticoid receptor (GR) immunoreactivity in the testis were examined. Corticosterone treatment significantly (P<.05) advanced testis descent and increased testis weight and 3betaHSD activity at puberty. In addition, adult CS rats presented higher levels of GR immunoreactivity in testicular tubules when compared to control and MS rats. No differences were found between control and MS rats. On this basis, we propose that the silencing of adrenocortical function during the SHRP could be finalized to preserve sexual maturation from the influence of glucocorticoid effects. As SHRP is unique to rodents, this phenomenon could be related to their successful reproductive strategy.

Animals↗
PubMed2000

Testis- and developmental stage-specific expression of hnRNP A2/B1 splicing isoforms, B0a/b.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) A2 and B1 are abundant nuclear proteins that bind to nascent RNAs synthesized by RNA polymerase II. Previously we had found that the splicing isoforms hnRNP B0a/b, from which the ninth exon of the A2/B1 gene is excluded, are abundantly expressed in testis. We postulated that B0a/b are testis-specific isoforms, and investigated the expression of A2/B1 and B0a/b in rat tissues and in postnatal development of rat testes using RNase protection assay, immunoblotting, and immunohistochemistry. We found that hnRNP B0a/b mRNAs are expressed in several tissues but that the testis alone expresses B0a/b proteins. A sequential study using neonatal rat testes demonstrated that B0a/b mRNAs are produced after 17 days of age, but not translated until 4 weeks of age when round spermatids appear in addition to spermatogonia and spermatocytes. Immunohistochemically, hnRNP A2/B1 isoforms are expressed during spermatogenesis from spermatogonia through round spermatids, whereas the expression of A1 is restricted to spermatogonia. This expression pattern in the rat testis is maintained from birth through adulthood. These results suggest that the expression of the hnRNP A2/B1 gene is partly regulated by a testis-specific post-transcriptional mechanism, and that the products of the A2/B1 gene, especially hnRNP B0a/b, are involved in spermatogenesis.

Animals↗
PubMed2001

Testis-specific and developmentally induced expression of a ghrelin gene-derived transcript that encodes a novel polypeptide in the mouse.

Ghrelin is a novel growth hormone-releasing peptide isolated from rat stomach. In the present study, we report expression of a ghrelin gene-derived transcript (GGDT) in the mouse testis. Analysis of GGDT cDNA revealed that the 68 bp sequence at the 5'-end was unique and the remaining 252 bp sequence was identical with the sequence encoded by exons 4 and 5 of mouse ghrelin gene. The 5'-unique sequence encoded 12 amino acid residues being in-frame with the C-terminal 42 amino acid sequence of mouse ghrelin. The 54-amino-acid polypeptide encoded by GGDT contained no apparent signal peptide sequence but possessed a nuclear localization signal-like sequence. Ghrelin mRNA was extensively expressed in the stomach, while GGDT was expressed only in the testis. The 5'-unique sequence of GGDT was identified between exons 3 and 4 of the ghrelin gene, indicating that GGDT was generated by alternative usage of the 68 bp exon as the testis-specific first exon. The GGDT expression in the testis was initiated and increased after 2 weeks of postnatal period. These results indicate that the expression of GGDT is regulated in testis-specific and developmental stage-specific manners.

Age Factors↗
PubMed1998

Testis-specific prohormone convertase PC4 processes the precursor of pituitary adenylate cyclase-activating polypeptide (PACAP).

The physiological substrate for proprotein convertase (PC) 4, which is expressed only in the testis, has remained unknown. Pituitary adenylate cyclase activating polypeptide (PACAP), originally isolated from the hypothalamus, exists as two amidated forms with 38 (PACAP38) and 27 (PACAP27) residues. PACAP-like immunoreactivity (PACAP-li) is found not only in the brain, but also in the peripheral tissues, and is especially abundant in the testis. Immunohistochemistry of the rat testis demonstrated strong PACAP-li in spermatids in the cap and acrosome phases. The nearly simultaneous expression of PC4 transcripts and PACAP-li in spermatids during spermatogenesis led to the hypothesis that PACAP precursor is processed by PC4. To investigate this possibility, rat pituitary GH4C1 cells were stably transfected with human PACAP cDNA, and some of these cells were co-transfected with mouse PC4 cDNA. The acid extracts of the cells were fractionated by reversed-phase HPLC. Each fraction was examined for PACAP-li using three antisera which recognize PACAP precursor, PACAP38 and/or PACAP27. Negligible PACAP-li that eluted with synthetic PACAP38 or PACAP27 was detected from cells transfected with PACAP cDNA; however, PC4 co-transfected cells showed marked PACAP-li peaks with the retention times for both PACAP38 and PACAP27. Moreover, Western blot analysis revealed immunostained bands, corresponding to the Mr for PACAP38 and PACAP27, in the PC4 co-transfected cells. Bioactivity, as indicated by stimulation of cAMP production in pituitary cell cultures, was found only in the extracts of PC4 co-transfected cells. These results provide evidence that PACAP precursor in the testis is a substrate for PC4. The processing of PACAP precursor by PC4 at a critical time in spermatogenesis suggests an important regulatory role of PC4 and PACAP in the maturation of germ cells in the testis.

Animals↗
PubMed1999

Expression of mitochondrial genes and of the transcription factors involved in the biogenesis of mitochondria Tfam, NRF-1 and NRF-2, in rat liver, testis and brain.

Mitochondrial function requires genes encoded in both mitochondrial and nuclear genomes. Tfam, the activator of mammalian mitochondrial transcription, is encoded in the nucleus and its expression has been shown in in vitro studies to be controlled by nuclear respiratory factors NRF-1 and NRF-2. In order to understand the physiological dependence of mitochondrial gene expression, we have analyzed in rat liver, testis and brain the expression level of mitochondrial genes in parallel with those of the three transcription factors. We found that: a) Tfam expression is down-regulated in rat testis, both at the protein and transcript level. The three-fold reduction in the abundance of Tfam protein in rat testis does not result in low steady-state levels of mitochondrial gene transcripts, suggesting that Tfam is in excess and does not limit transcription in vivo; and b) NRF-1 and NRF-2 (alpha, beta and gamma subunits) mRNAs were analyzed by Northern blotting; for each mRNA, several transcripts were observed as well as tissue-specific patterns of expression. The mRNA steady-state levels of NRF-1 and NRF-2 were higher in testis than in liver or brain. These data suggest that the low expression level of Tfam found in testis is not due to decreased NRF-1 and/or NRF-2 expression and further suggest the existence of tissue-specific post-transcriptional regulatory mechanisms for the expression of NRF-1/NRF-2 genes.

Animals↗
PubMed1997

Localisation and regulation of 17beta-hydroxysteroid dehydrogenase type 3 mRNA during development in the mouse testis.

The final step in the biosynthesis of testosterone is the reduction of androstenedione to testosterone catalysed by the enzyme 17beta-hydroxysteroid dehydrogenase (17betaHSD). Five isoforms of the enzyme have been identified in the mouse and the type 3 isoform has been shown to be the predominant reductive form present in the adult human and mouse testis. In this study the regulation of 17betaHSD type 3 isoform mRNA levels and the cellular localisation of the enzyme mRNA have been studied in the mouse testis. To examine regulation of 17betaHSD type 3 mRNA expression in the testis, mRNA levels were measured during development in normal mice and in mice lacking circulating gonadotrophins (hpg) or functional androgen receptors (Tfm). In these mutants testicular descent does not occur at the normal time (25 days) and control animals were, therefore, rendered cryptorchid at 19 days. In neonatal mice, it has been shown a peak of type 3 expression occurs around day 5 and this was found to be normal in all groups in the current study. In normal animals there was a marked increase in type 3 isoform expression between 25 and 30 days and this continued into adulthood. In cryptorchid animals the increase in type 3 mRNA levels after 25 days was less marked than in untreated controls and by 90 days was about 15% of normal animals. In Tfm mice, levels of 17betaHSD type 3 mRNA failed to show any increase around puberty (25 days) and in adult Tfm mice, levels were less than 1% of cryptorchid controls. In hpg mice, levels of type 3 mRNA increased slowly after puberty and were about 30% of cryptorchid controls by 90 days. Studies using in situ hybridisation showed that the type 3 isoform was expressed only in the interstitial tissue of the adult normal mouse testis. No specific hybridisation could be determined in adult hpg or Tfm testes. Results show that 17betaHSD type 3 is an interstitial enzyme in the testis and is, probably, localised in the Leydig cells. During neonatal development expression of 17betaHSD type 3 is independent of gonadotrophin action while the increase in type 3 expression at puberty is primarily dependent upon androgen action although testicular descent and gonadotrophins are also required.

17-Hydroxysteroid Dehydrogenases↗
PubMed2002

Expressed sequence tag analysis of expression profiles of zebrafish testis and ovary.

In the present study, two gonad cDNA libraries from zebrafish testes and ovaries were constructed and a total of 1025 expressed sequence tag (EST) clones were generated from the two libraries: 501 from the testis library and 524 from the ovary library. A total of 641 of the EST clones were identified to share significant sequence identity with known sequences in GenBank, representing at least 478 different zebrafish genes. In order to understand the molecular compositions of the two gonad organs, the expression profiles of the identified clones in these two gonad cDNA libraries were analyzed. Both gonad libraries have a higher portion of clones for nuclear proteins and a lower portion for proteins in translational machinery, cytoskeleton and mitochondria than our previously characterized whole-adult cDNA library. Most abundant cDNA clones in the two gonad libraries were identified and over 10% of ovary clones were found to encode egg membrane proteins (zona pellucida or ZP proteins). Furthermore, the testis library showed a more even distribution of cDNA clones with relatively fewer abundant clones that tend to contribute redundant clones in EST projects; thus, the testis library can supply more unique and novel cDNA sequences in a zebrafish EST project. Another aim of this study is to identify cDNA clones that can be used as molecular markers for the analysis of the gonad development in zebrafish. Eleven potential clones were selected to analyze their expression patterns by Northern blot hybridization. Most of them showed a specific or predominant expression in the expected testis or ovary tissue. At last, four of the clones were found, by section in situ hybridization, to be expressed specifically in the germ cells of the testis or ovary and thus they are suitable molecular markers for analyses of spermatogenesis and oogenesis.

Animals↗
PubMed2003

Effects of 3,3',4,4',5-pentachlorobiphenyl, a coplanar polychlorinated biphenyl congener, on cultured neonatal mouse testis.

3,3',4,4',5-Pentachlorobiphenyl (PCB126), a congener with a planar configuration, has been established to have relatively strong toxicities similar to those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) via aryl hydrocarbon receptors. We investigated the effects of this coplanar PCB on mammalian early spermatogenesis and steroidogenesis in a mouse neonatal testicular organ culture system. Testes collected from newborn mice were subjected to organ culture in medium containing 0, 10, 100 or 1000 nM PCB126. Histochemical analysis revealed that the BrdU-labeling indices of both spermatogenic cells and Sertoli cells were unchanged in all testis specimens exposed to the coplanar PCB. CYP1A1 and steroidogenic enzymes (P450scc, P450c17, 3beta-HSD and 17beta-HSD) mRNA levels were determined by semiquantitative RT-PCR. The CYP1A1 mRNA level in cultured testis was significantly increased by PCB126 in a dose-dependent manner. Although mRNA levels of 3beta-HSD and 17beta-HSD were unchanged, the P450scc mRNA level was significantly down-regulated by PCB126 in a dose-dependent manner. In contrast, the P450c17 mRNA level was significantly higher in 1000 nM PCB126-exposed testis than in control testis. These results suggest that the coplanar PCB does not alter the proliferative activity of spermatogenic cells and Sertoli cells in neonatal testis, but that it directly affects the expression of steroidogenic enzyme genes.

Animals↗
PubMed2003

Immunohistochemical investigations of the autonomous innervation of the cervine testis.

The innervation of the cervine testis was studied in 6 roe deers, 7 red deers and 14 fallow deers. The results for the three species are rather similar. With anti-sera to neurofilament (NF) and neuron specific enolase (NSE), all small and large nerve fascicles can be demonstrated, but single fibers are incompletely stained. Immunoreactions against protein gene product-9.5 (PGP-9.5) and GAP-43 (growth-associated protein-43) are better suited to depict the complete innervation pattern. Bundles of the superior spermatic and inferior spermatic nerves reach the testis via three access routes as funicular, mesorchial and caudal nerve contributions. We found no morphological evidence that the nerves in the cervine testis are directly involved in regulating Leydig cell function or seminiferous tubular motility. The majority of the testicular nerves are associated with the testicular arteries, but the musculature in the walls of the venous plexus pampiniformis is also innervated. All vascular nerve fibers represent postjunctional sympathetic axons displaying a strong dopamine-beta-hydroxylase (DBH) activity, mostly co-expressed with neuropeptide Y (NPY). The presence of cholinergic fibers in the testis of the deer is only sporadic and probably of no functional importance. In all three species of deer, a small quantity of myelinated nerve fibers is encountered in spermatic cord and tunica albuginea and regarded as afferent. The viscerosensory quality in the testicular intrinsic innervation is very likely mediated by the CGRP (calcitonin gene-related peptide)-positive fibers that run independently from the testicular vessels and end in the connective tissue of spermatic cord and tunica albuginea. The testis of the red deer contains significantly more VIP (vasoactive intestinal polypeptide)-positive axons than that of roe and fallow deer. The nerve density in the interior of the testicular lobules shows no regional differences, but there are age- and season-related changes that correlate with the developmental and functional state of the seminiferous tubules. Small testes with solid and narrow tubules, as seen in the prepuberal phase and during seasonal reproductive quiescence, are better innervated than large testes with expanded and spermatogenetically active seminiferous tubules.

Acetylcholinesterase↗
PubMed2003

Melatonin preserves arachidonic and docosapentaenoic acids during ascorbate-Fe2+ peroxidation of rat testis microsomes and mitochondria.

The pineal hormone melatonin (N-acetyl, 5-methoxytryptamine) was recently accepted to act as an antioxidant under both in vivo and in vitro conditions. In this study, we examined the possible preventive effect of melatonin on ascorbate-Fe(2+) lipid peroxidation of rat testis microsomes and mitochondria. Special attention was paid to the changes produced on the highly polyunsaturated fatty acids C20:4 n6 and C22:5 n6. The lipid peroxidation of testis microsomes or mitochondria produced a significant decrease of C20:4 n6 and C22:5 n6. The light emission (chemiluminescence) used as a marker of lipid peroxidation was similar in both kinds of organelles when the control and peroxidized groups were compared. Both long chain polyunsaturated fatty acids were protected when melatonin was incorporated either in microsomes or mitochondria. The melatonin concentration required to inhibit by 100% the lipid peroxidation process was 5.0 and 1.0mM in rat testis microsomes and mitochondria, respectively. IC 50 values calculated from the inhibition curve of melatonin on the chemiluminescence rates were higher in microsomes (4.98 mM) than in mitochondria (0.67 mM). The protective effect observed by melatonin in rat testis mitochondria was higher than that observed in microsomes which could be explained if we consider that the sum of C20:4 n6+C22:5 n6 in testis microsomes is two-fold greater than present in mitochondria.

Animals↗
PubMed2002

A novel structure-specific endonuclease activity associated with polypyrimidine-tract binding (PTB) related protein from rat testis.

Nucleases are involved in the processing of various intermediates generated during crucial DNA metabolic processes such as replication, repair, and recombination and also during maturation of RNA precursors. An endonuclease, degrading specifically single-stranded circular DNA, was identified earlier in rat testis nuclear extract while purifying a strand-transfer activity. We are now reporting the purification of this endonuclease, which is a monomeric 42 kDa protein, from rat testis to near-homogeneity. In addition to degrading single-stranded circular DNA, it nicks supercoiled plasmid DNA to generate relaxed DNA and does not act on linear single-stranded or double-stranded DNA. It also makes specific incisions at the single-strand/duplex junction of pseudo-Y, 3'- and 5'-overhangs and 3'- and 5'-flap structures. Other structures such as mismatch, insertion loop, and Holliday junction are not substrates for the testis endonuclease. In contrast to FEN1, the testis endonuclease makes asymmetric incisions on both strands of the branched structures, and free single-stranded ends are not necessary for the structure-specific incisions. Neither 5'-3' nor 3'-5' exonuclease activity is associated with the testis endonuclease. The amino acid sequences of tryptic peptides of the 42 kDa endonuclease show near-identity to polypyrimidine-tract binding protein (PTB) that is involved in the regulation of splicing of eukaryotic mRNA. The significance of the results on the association of structure-specific endonucleae activities with PTB-related protein is discussed.

Amino Acid Sequence↗
PubMed2003

Primary adenocarcinoma of the rete testis.

We report a case of adenocarcinoma of the rete testis in a 44-year-old man, presented intially with a hydrocele and later with signs of infection in the affected hemiscrotum. Multiple focal lesions within the testis appeared 6 months later in ultrasounds. After high inguinal orchiectomy, histology revealed a primary adenocarcinoma of the rete testis. Adenocarcinoma of the rete testis is a rare a highly malignant tumour originating in the mediastinum of the testis. Slightly over 40 cases have been reported in the literature. The treatment of choice is radical orchiectomy. Prognosis is poor; as mainly as 40% of patients die within the first year of diagnosis.

Adenocarcinoma↗
PubMed2003

Testis conserving chemotherapy in germ cell cancer: its potential to increase understanding of the biology and treatment of carcinoma-in-situ.

Prompted by recognition of the potential of chemotherapy to increase the success of testis conserving surgery in patients with germ cell cancer, background and outcome data are reviewed and their contribution to the ongoing debate about how germ cell cancer develops discussed. The review is based on three previous studies of: a) time trends in tumour size in 578 personal series of all stages of testis cancer treated since 1978; b) impact of chemotherapy on actuarial risk of tumours in contralateral testis examined on 1221 patients treated in trials through the Anglian Germ Cell Cancer Consortium; and c) testes conservation attempted using chemotherapy in 78 patients. Since 1978 tumour size has decreased from 4.8 to 3.0 cms while cure has gone from 77 to 97%. There was no overall long term reduction in second cancers beyond 10 years in stage 1 patients after orchidectomy alone compared to stage 1 or metastatic disease patients receiving chemotherapy though the incidence was non significantly lower up to 10 years particularly in those patients receiving etoposide based combination. Testis conservation was initially successful in 28 of 78 (36%). An additional 25 (32%) had no viable cancer in orchidectomy specimen. In the 28 primary tumours cured by chemotherapy there was a 26% late relapse rate between 5 and 10 years (all cured by orchidectomy) compared to less than 5% in those cured with established metastases. In conclusion, testis conservation with chemotherapy is safe and feasible, though relapse is too frequent for routine service use. Confirmation of the high frequency of late relapse by others has raised the question whether these recurrences are due to post pubertal events reinducing CIS in intrauterine oestrogen primed germ cells and highlights the potential of testes conservation studies to better understand germ cell cancer development.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Endocrine function in patients treated for carcinoma in situ in the testis with irradiation.

CIS is found in the contralateral testis in 5% of the patients with testicular germ cell cancer. The management of CIS in the contralateral testis is important because the majority - if not all - cases of CIS will progress to invasive disease without treatment. It is well documented that testicular irradiation with a total dose of 14-20 Gy (2 Gy x 7-10) is an effective and safe treatment for CIS in the contralateral testis in patients with unilateral testicular germ cell cancer. However few relapses of testicular cancer have been observed in testis treated with these regimens and the data on 14 Gy are sparse. One study has indicated that more radiotherapy with lower doses per fraction could be useful, but more data are needed to confirm this. Endocrine testicular function has been shown to be impaired already before treatment in patients with CIS and is further impaired after testicular irradiation with 14-20 Gy (2 Gy x 7-10) and only minor dose dependency is seen in the impairment of Leydig cell function. The optimal treatment of CIS in the contralateral testicle in patients orchidectomised for testicular cancer seems to be local radiotherapy of the testis with CIS in order to preserve at least a part of the Leydig cell function. However, the optimal dose level has to be defined.

Carcinoma in Situ↗