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PubMed2000

Life expectancy, antagonistic pleiotropy, and the testis of dogs and men.

BACKGROUND: Prostate cancer and benign prostatic hyperplasia are important age-related prostatic diseases that are under the influence of testicular hormones. However, the disparity between male and female life expectancy within the human population cannot be explained solely by the prevalence of prostatic disease-related mortality. The purpose of this paper is to explore the possibility that the testis exerts a detrimental effect on life span. METHODS: First, we review previously published and unpublished data on the influence of the testis on the life span of dogs and men. Aging in pet dogs and men is then discussed in terms of evolutionary theory, emphasizing the significance of a prolonged postreproductive life span and possible consequences of late-acting deleterious genes in these two species. Finally, we present preliminary data that orchiectomy can reduce DNA damage within the brain of elderly male dogs. RESULTS AND CONCLUSIONS Taken together, these observations raise the intriguing possibility that interventions to antagonize the testis might have much broader therapeutic applications that will extend well beyond the treatment of prostate cancer.

Adolescent↗
PubMed2001

Cellular expression of retinal dehydrogenase types 1 and 2: effects of vitamin A status on testis mRNA.

We examined expression of retinal dehydrogenase (RALDH) types 1 and 2 in liver and lung, and the effect of vitamin A status on testis expression by in situ hybridization. Liver expressed RALDH1 and RALDH2 only in stellate cells and hepatocytes, respectively. Lung expressed RALDH1 and RALDH2 throughout the epithelia of the airways, from the principal bronchi to the respiratory bronchiole. Vitamin A-sufficient rats expressed RALDH1 in spermatocytes, with less intense expression in spermatogonia and spermatids, and expressed RALDH2 in interstitial cells, spermatogonia, and spermatocytes. Neither Sertoli nor peritubular cells showed detectable RALDH1 or RALDH2 mRNA. Vitamin A deficiency produced a sevenfold increase in RALDH1 and a 70-fold decrease in RALDH2 mRNA in testis. In each case, the net change reflected extensive loss of germ cells, increased intensity of expression in residual germ cells, and expression in Sertoli and peritubular cells. Low-dose RA relatively early during vitamin A depletion supported spermatogenesis and affected expression of both RALDHs, but did not reinstate "vitamin A normal" expression patterns. These results show that: RALDH1 and RALDH2 have distinct mRNA expression patterns in multiple cell types in three vitamin A target tissues; RALDH expression occurs in cell types that express cellular retinol-binding protein and retinol dehydrogenase isozymes (except stellate cells, for which retinol dehydrogenase expression remains unknown); vitamin A deficiency and RA supplementation affects the loci and intensity of RALDH mRNAs in testis; and low-dose RA does not substitute completely for retinol. Overall, these data provide insight into the unique functions of RALDH1 and RALDH2 in retinoid metabolism.

Aldehyde Oxidoreductases↗
PubMed2001

Heat-shock resistance in experimental cryptorchid testis of mice.

Cryptorchidism is commonly used for research on spermatogenesis. However, there are few comparative investigations about the strain differences in mice, especially in long-term experiments. In the present study, the authors demonstrate its specific dynamics in the MRL/MpJ mouse strain, and discuss the cause of strain differences. In the mouse strains A/J BALB/c, C3H/He, and C57BL/6, after 2 weeks of experimental cryptorchidism, the ratios of the cryptorchid testis weight against the intact one were 0.38+/-0.05, 0.43+/-0.05, 0.38+/- 0.02, and 0.44+/-0.14, respectively. On the other hand, in the MRL/MpJ strain it was shifted to 0.69+/-0.08. The details of this strain difference were compared by calculation of germ cells with the Sertoli cell index at 2 weeks after operation. The indices of spermatogonia in all strains were not significantly different; however, in MRL/MpJ mice remarkable numbers of late spermatocytes and round spermatids were detected. The decrease of the testis weight ratio was similar until 10 days in the C57BL/6 and MRL/MpJ strains, but continued in C57BL/6 until 21 days, whereas in MRL/MpJ mice it plateaued after 10 days. Northern blot analysis for heat shock protein 70-2 using total RNA prepared from the cryptorchid and intact testes at 2 weeks after operation revealed that the expression was decreased in the cryptorchid testis of C57BL/6, but not MRL/MpJ mice. The results suggested that heat-resistant germ cells were present in MRL/MpJ, originating possibly from the genetic background.

Animals↗
PubMed2001

Elevated levels of the polyadenylation factor CstF 64 enhance formation of the 1kB Testis brain RNA-binding protein (TB-RBP) mRNA in male germ cells.

The single copy mouse Testis Brain RNA-Binding Protein (TB-RBP) gene encodes three mRNAs of 3.0, 1.7, and 1.0 kb which only differ in their 3' UTRs. The 1 kb TB-RBP mRNA predominates in testis, while somatic cells preferentially express the 3.0 kb TB-RBP mRNA. Here we show that the 1 kb mRNA is translated several-fold more efficiently than the 3 kb TB-RBP in rabbit reticulocyte lysates and cells with elevated levels of the 1 kB TB-RBP mRNA express high levels of TB-RBP. To determine if the cleavage stimulatory factor CstF 64 can modulate the alternative splicing of the TB-RBP pre-mRNA and therefore TB-RBP expression, CstF 64 levels and binding to alternative polyadenylation sites were examined. CstF 64 is abundant in the testis and preferentially binds to a distal site in the TB-RBP pre-mRNA that produces the 3 kb TB-RBP. Moreover, upregulation or overexpression of CstF 64 increases the poly(A) site selection for the 1 kb TB-RBP mRNA. We propose that the level of the polyadenylation factor CstF 64 modulates the level of TB-RBP synthesis in male germ cells by an alternative processing of the TB-RBP pre-mRNA.

3' Untranslated Regions↗
PubMed1982

Microvasculature of the mouse testis and excurrent duct system.

The microvascular architecture of the mouse testis and excurrent duct system was examined by a casting method with the aid of scanning electron microscopy and by sectioning techniques for light and transmission electron microscopy. Two fundamental types of peritubular capillary arrangements were noted in relation to the tubules. The first type most typically appeared in the testis. In this type, peritubular capillaries interconnected intertubular blood vessels to form a rope-ladder-like structure. The length of the individual peritubular capillaries was short, and a number of the capillaries encircled each tubule. Adjacent tubules shared a single layer of capillaries. The vascular organization of the ductuli efferentes and of the middle segment of the epididymis was also of this type, but the number of peritubular capillaries was much fewer compared with that of the testis. In the second type, the peritubular capillaries formed a network encircling each tubule in its subepithelial layer. The capillary organization in the initial and terminal segments of the epididymis and the ductus deferens belonged to the second type. In the distal part of the ductus deferens, a prominent venous plexus was formed in the most peripheral subepithelial layer.

Animals↗
PubMed1982

The contribution of the mesonephros to the development of the sheep fetal testis.

In this study, which was performed on 52 sheep fetuses aged 24 to 85 days, we examined the relationship between testicular development and the "giant" mesonephric nephron, a peculiar structure consisting of a large glomerulus and multiple tubules. The development of the testis occurred in two phases. The preparatory phase began at day 24 of gestation, evolved simultaneously with the involution of the glomerulus of the giant nephron, and was characterized by mobilization of the glomerular cells and by their colonization of the genital ridge. By day 31, a prominent mass of migrating mesonephric cells had developed; it extended uninterrupted from the giant glomerulus into the gonad where the mesonephric cells associated with the germinal cells forming the cellular template from which the testicular cords later became assembled. At complete involution of the glomerulus (day 52), the migratory mass implanted on the tubules of the giant nephron, which thus became continuous with the gonad. During the organizational phase, which began at day 29 with the formation of the tunica albuginea, the various components of this continuum became progressively organized along a testis-to-mesonephros direction into seminiferous cords, tubuli recti, the cords of the rete testis, and the ductules efferentes. These observations show that, in the sheep, the precursors of the Sertoli cells are mesonephric in origin, and that the genital tract proximal to the epididymis differentiates from a single mesonephric nephron.

Animals↗
PubMed1986

Comparison of lectin-staining pattern in testis and epididymis of gerbil, guinea pig, mouse, and nutria.

The testis and epididymis of gerbil, guinea pig, nutria, and mouse were studied after staining with seven rhodamine-conjugated lectins to disclose the distribution of glycoproteins with different sugar residues. In the testis, the lectins showed a variable affinity for Leydig cells, tubular basement membrane, cytoplasm, acrosome, and plasma membrane of maturing spermatids as well as for Sertoli cell extensions. During acrosomal development, the staining pattern showed characteristic changes with different lectins indicating a gradual processing of the glycoprotein components. The staining in the Sertoli cell extensions displayed a cyclic change linked with the release of spermatozoa. A nuclear staining was prominent in zygotene and pachytene spermatocytes in the mouse, weak in the nutria, but absent in gerbil and guinea pig. The principal cells of epididymis showed a lectin-stained Golgi region as well as a similar staining in the apical surface, microvilli, and tubular contents. This staining was most prominent in the caput/corpus regions with some interspecies differences indicating the epididymal areas active in secretion. Narrow cells active in absorption of testis-derived material were lectin-positive in the initial segment of mouse, gerbil, and nutria epididymis. Large light cells with a strong affinity for some lectins were found in the proximal cauda of gerbil and guinea-pig epididymis. In the nutria, corresponding cells were arranged as islands within the low epithelium. The distal cauda of mouse, gerbil, and nutria was the site for lectin-stained light cells interspersed among the low principal cells. It is concluded that the high and low light cells may be active in the absorption and phagocytosis of residual bodies/cytoplasmic droplets and surplus epididymal secretory material, respectively. Thus, labeled lectins formed a useful tool in the analysis of glycoprotein distribution, processing, secretion, absorption, and degradation in the male reproductive tissues.

Animals↗
PubMed1990

Distribution of sodium-potassium ATPase in the rat testis and epididymis.

Sodium-potassium ATPase (Na+K(+)-ATPase) is a ubiquitous plasma membrane enzyme which uses the hydrolysis of ATP to regulate cellular Na+ and K+ levels and fluid volume. This ion pumping action is also thought to be involved in fluid movement across certain epithelia. There are several different genes for this enzyme, some of which are tissue specific. Using an antibody specific for the catalytic subunit of canine kidney Na+K(+)-ATPase, we have localized immunoreactivity in the seminiferous and epididymal epithelium of rats of various ages. There was no specific staining of 10-day-old rat testis. Faint staining was detected at 13 days and appeared to be associated with the borders of Sertoli cells. At 16 days prominent apical and lateral staining but no basal staining of Sertoli cell membranes was observed. This type of distribution continued until spermatids were present in the epithelium. In the adult rat testis, specific staining was detected in Sertoli cell crypts associated with elongating spermatids, and on the apical and lateral Sertoli cell membrane. In some instances immunoreactivity was concentrated at presumed sites of junctional specializations. In the excurrent ducts of immature and mature rats, Na+K(+)-ATPase staining was heavy in the efferent ducts and somewhat lighter in the epididymis. In all regions, the staining was basolateral although there were variations in intensity among the different parts of the epididymis. These results show 1) that rat testis and epididymal Na+K(+)-ATPase share some immunological determinants with the canine enzyme; 2) that the epididymal enzyme is located in the conventional basolateral position; and 3) that the distribution of Sertoli cell Na+K(+)-ATPase is probably apical and lateral rather than basal.

Aging↗
PubMed1975

An angiographic study of the fox testis in various stages of sexual activity.

The arteries and veins of the fox testis were studied using an angiographic technique. The postnatal development of the testis involved only minor modification of the vasculature. In the non-breeding season both the arteries and veins of the adult fox testis undergo extensive spiralization which completely disappears during the breeding season. When the sequence of morphological changes in blood vessels are related to available data on changes in testicular size, blood flow and connective tissue content, it is obvious that the vascular spiralization is passive and related to shrinkage of the organ and dose not primarily influence the testicular blood flow.

Angiography↗
PubMed1984

Endocytosis in epithelial cells lining the rete testis of the rat.

The endocytic activity of the low cuboidal cells lining the rete testis was analyzed by electron microscopy following injection of various tracers into the lumen of these anastomotic channels. At 1 and 5 minutes after injection, cationic ferritin (CF) and concanavalin A-ferritin (Con A) were seen bound to the apical plasma membrane and to the membrane of subjacent vesicles or invaginations connected to this apical membrane. At 30 and 60 minutes, these tracers were found in intracytoplasmic vesicles and in vesicles connected to the lateral or basal plasma membrane as well as in the lateral intercellular space and in the lamina lucida of basal lamina. At 30 minutes, CF and Con A also appeared in the matrix of pale multivesicular bodies while at 1 hour dense multivesicular bodies were labeled. At 2 hours and later time intervals, the tracers accumulated in dense granules identified as lysosomes. Native ferritin (NF), concanavalin A-ferritin in presence of alpha-methyl-D-mannoside, and horseradish peroxidase or albumin bound to colloidal gold were all to be incorporated by the lysosomal system of these epithelial cells, as just described for CF and Con A, but these various tracers were not bound to the apical plasma membrane or to the membrane of cytoplasmic vesicles, nor were they found in the intercellular spaces or the lamina lucida at the base of the cells. Thus, the epithelial cells of the rete testis do not appear to be only involved in the uptake of substances from the lumen and their disposal by the lysosomal system, but also appear to contribute to the transport of certain macromolecules from the lumen to the laterobasal surfaces of the cells. These cells may thus play a role in determining the composition of the rete testis fluid.

Albumins↗
PubMed1975

Surgical sterilization by vasectomy and its effects on the structure and function of the testis in man.

The early and late effects of vasectomy have been investigated in 40 men. Besides histopathological examination, the volume of the testis and its total content of testosterone-screting Leydig cells have been measured. The volume of the testis showed a wide normal variation (5-3-23-3 ml) but was not significantly changed by vasectomy. One month after vasectomy widespread degeneration of the germinal epithelium, thickening of the basement membrane and some intertubular fibrosis were observed. Spermatogenesis had ceased. However, cases examined 2-31/2 years later showed an essentially normal structure with active spermatogenesis. This indicates that regeneration does occur spontaneously, even without recanalization. Whether the sperms formed are functionally normal remains uncertain. The normal total Leydig cell volume was 2-2 plus or minus 0-4 ml/testis in young adults and showed a modest increase after vasectomy, rising to 2-5 plus or minus 0-5 ml after 1 month and 2-6 plus or minus 0-5 ml after 2-31/2 years. The findings have been discussed in the light of Steinach's (1927) original hypothesis that vasectomy can rejuvenate ageing males by improving the endocrine function of the testis.

Adult↗
PubMed1977

Torsion of the testis.

A series of 56 proved cases of torsion of the testis is reviewed. The condition is rare, only 2 patients per year being admitted to a large general hospital of 800 beds. The aim of this study was to assess the fate of testes in relation to the duration of symptoms: if less than 12 hours the outlook is good, between 12 and 24 hours survival of the testis is possible, over 24 hours the testis is most likely to be beyond salvage and beyond 48 hours there is virtually no hope of testicular survival and orchidectomy will be necessary.

Adolescent↗
PubMed2003

Regionally distinct potencies of mouse XY genital ridge to initiate testis differentiation dependent on anteroposterior axis.

In mouse gonadal differentiation, the center-to-pole Sry expression pattern suggests the regionally distinct potencies of the genital ridge, which induce testis differentiation. In this study, we examined the anteroposterior axis-dependent differences in testis-differentiation potencies by using cultures of anterior, middle, and posterior segments of the XY genital ridge. The inducible pattern of Sertoli cell differentiation showed a center-to-pole wave similar to the initial Sry expression pattern. In contrast, the ability to induce Leydig cell differentiation emanated from the anterior segment and then spread to the posterior side. These findings suggest the presence of two distinct dynamic waves in the capacity of the genital ridge to induce Sertoli or Leydig cell differentiation at early phases of testis differentiation.

Animals↗
PubMed1990

Micro two-dimensional gel electrophoresis of serum and testis esterases from different strains of mice.

Two-dimensional electrophoresis with time-dependent polyacrylamide gradient gel electrophoresis (PAGGE) in the second dimension was applied to the separation of native molecular forms of esterases from serum and testis of four strains of mice (C57BL/6J, Swiss OF1, F1 hybrid derived from these two populations and Tfm). In Phast System, a modified pH 3-9 gradient, a linear 8-25% gel gradient and a migration time corresponding to 300 Vh, were found to provide the best conditions for esterase analysis. About 70 esterase-active fractions could be separated with good reproducibility. The variants were characterized by their pI (3.9-7.35), their relative mobility and the visual estimation of their susceptibility towards neuraminidase and different esterase inhibitors. In the two tissues, the distribution of the esterase variants corresponded to a 50-500 kDa molecular mass range of calibration proteins, but most of the serum and testis-specific isoforms were confined to the 59-72 kDa range. All serum variants contained a terminal N-acetylneuraminic acid residue, whereas only the testicular esterases in common with those in serum appeared sensitive to neuraminidase. Cholinesterases with a low relative mobility and carboxylesterases with a high relative mobility were detected in serum, while carboxylesterases accounted for the greatest part in the testis which also contained cholinesterases and acetylesterases. Minor interspecies differences were found between C57BL/6J and Swiss OF1 esterases. The expression of two variants which differed between these two species seemed intermediate for the hybrid originating from these two populations. Two new spots were detected in the two-dimensional map of esterases from the strain bearing the Tfm mutation.

Animals↗
PubMed1987

Molecular characterization of the testis specific c-abl mRNA in mouse.

The c-abl gene encodes a protein tyrosine kinase and is transcribed from at least two promoters giving rise to transcripts of two size classes of approximately 5 and 6 kb in length. These mRNAs only differ in their most 5' exon and encode proteins of similar size but with different N-termini. In the mouse testis an additional abundant c-abl mRNA of 4 kb is detected. This mRNA was shown to be expressed in the haploid male germ cells of the adult mouse. Here we describe the cloning and molecular characterization of a cDNA representing the testis specific c-abl transcript. We show that the 4 kb c-abl mRNA arises from alternative polyadenylation of an RNA transcribed from the same promoter as the 5 kb mRNA. The site of polyadenylation is unusual in this shorter transcript as it is not preceded by the highly conserved hexanucleotide AAUAAA. The use of this polyadenylation site removes 1.2 kb of 3' sequences present in the somatic c-abl mRNAs, but does not affect the main open reading frame of the transcript. Using in situ hybridization on whole testis sections it is shown that the 4 kb c-abl mRNA is most abundant in the elongating spermatids.

Animals↗
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↗
PubMedDate not supplied

Androgens in various fluid compartments of the rat testis and epididymis after hypophysectomy and gonadotropin supplementation.

Hypophysectomized male rats were administered LH or LH + FSH for 14 days and subjected to in vivo micropuncture collection of reproductive tract fluids to determine if FSH alters the compartmentalization of testosterone in the rat testis or of 5 alpha-dihydrotestosterone (DHT) in the epididymis. Testosterone and DHT concentrations were determined in cardiac blood serum, testicular venous serum, testicular interstitial fluid, and seminiferous tubule fluid, and in intraluminal fluid and tissue extracts from the caput and cauda epididymidis. Testosterone is the predominant androgen in the testis, and compared with control values, concentrations in venous sera, interstitial fluid, and tubule fluid were returned to values indistinguishable from controls by supplementation with 24 micrograms LH/day. 24 micrograms LH + 24 micrograms FSH/day did not augment the intratubular partition of testosterone. Epididymal DHT values were returned to control levels by LH alone, but additional supplementation with FSH significantly increased DHT from the caput epididymidis even further. It is speculated that FSH does not alter the compartmentalization of androgens in the rat testis, but may play a role in retaining androgens in the epididymis.

Androgens↗
PubMedDate not supplied

Germ cell degeneration in the contralateral testis of the guinea pig with unilateral torsion of the spermatic cord. Quantitative and ultrastructural studies.

This study evaluated the long term effects of unilateral torsion of the spermatic cord on the contralateral testis of guinea pigs, employing both fine structural and quantitative studies. Young, adult Hartley strain guinea pigs were divided into six experimental groups (12 animals per group). The first three groups consisted of 36 animals in which unilateral torsion was surgically induced. In group I (torsion maintained), unilateral torsion of the spermatic cord was maintained until the day of sacrifice; in group II (torsion and untwist), torsion of the spermatic cord was maintained for 8 to 12 hours, then the spermatic cord was untwisted and the testis was retained until the day of sacrifice. In group III (torsion and orchiectomy), testes were removed after 8 to 12 hours of spermatic cord torsion. The second three groups consisted of 36 animals: group IV (unilateral orchiectomy), group V (unilateral sham operation), and group VI (pentobarbital injection alone), which served as controls. One half of the animals from each group were killed after 4 months and the other half were killed after 8 months. The most frequently observed histologic changes in the contralateral testes of the experimental animals were focal disorganization and exfoliation of immature germ cells into the lumen. Severe damage, with almost complete absence of germ cells, was noted only in an occasional tubule. Quantitative evaluation of the germ cells of the contralateral testis revealed significant loss of germ cells in groups I, II, and III after 4 months, and in groups I and II after 8 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗