Development of enzyme activity in the Leydig cells of the mouse testis.
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Animals↗
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Development of Sertoli cell populations in organ culture of immature pig testis.
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Animals↗
The genetic control and germ cell kinetics of the female and male germ line in mammals including man.
The female germ line (germ cell lineage, Keimbahn) is provided with only one proliferation wave, the oogenic, whereas male gametogenesis involves two successive waves: prespermatogenic, which corresponds to the female proliferation wave, and spermatogenesis, which is responsible for the immense number of male gametes produced in mature testes. Both male proliferation systems are linked by the transitional or T prospermatogonia. Using the reverse percentage of labelled metaphases method, it has been shown that the first differences between female and male germ cells can be identified by the end of the first wave, when oogonia and multiplying or M prospermatogonia are proliferating. This prenatal first wave of proliferation of male germ cells was also demonstrated in man and ceases around the 22nd week of pregnancy. Spermatogenesis involves a stock of stem cells (stem spermatogonia), a flexibly reacting pool of undifferentiated spermatogonia and several generations of differentiating spermatogonia, which proliferate almost exponentially. Furthermore, it consists of spermatocytes and haploid spermatids transforming into spermatozoa. The oocytes pass through the preleptotene stage, synthesizing DNA, and thereafter traverse the meiotic prophase up to the diplotene stage. In mammals they act as 'pre-embryos' in a similar but to a lesser degree than oocytes of amphibia and insects. The maternal chromosomes are largely responsible for the development of the embryo, the paternal genome for the development of the extra-embryonic tissue. The synthesis of transgenic animals is a powerful weapon in the armoury of geneticists, as has recently been demonstrated: a 14 kb genomic DNA fragment (Sry) is sufficient to induce testis differentiation and subsequent male development when introduced into chromosomally female mouse embryos.
Animals↗
Impaired spermatogenesis and male fertility defects in CIZ/Nmp4-disrupted mice.
CIZ (Cas interacting zinc finger protein), also called Nmp4 (nuclear matrix protein 4), is a nucleo-cytoplasmic shuttling transcription factor that regulates the expression of collagen and matrix metalloproteinases. CIZ/Nmp4 was originally cloned by its binding to p130(Cas), a focal adhesion protein, and was recently shown to suppress BMP2 (bone mophogenetic protein 2) signalling. To explore the physiological role of CIZ/Nmp4, we disrupted CIZ/Nmp4-gene by inserting beta-galactosidase and neomycin resistance genes into the 2nd exon of CIZ/Nmp4-gene, which is utilized by all the sequenced alternative forms. CIZ-/- mice were born and grew to adulthood. Although they tend to be smaller than wild-type mice, no pathological abnormality was observed except in the testis. Histological analysis of the testes revealed variable degrees of spermatogenic cell degeneration within the seminiferous tubules of CIZ-/- mice, resembling the histology of the 'Germinal-cell aplasia with focal spermatogenesis'. Some of the CIZ-/- male mice developed infertility. TUNEL assay on testis sections revealed an increased occurrence of apoptosis of spermatogenic cells in the testes of CIZ-/- mice. CIZ/Nmp4 was co-localized with Smad1 in the testis, suggesting that a disregulation of BMP signalling could cause these phenotypes. These results suggest that CIZ/Nmp4 plays roles in the progress and the maintenance of spermatogenesis.
Aging↗
Spontaneous development of organ-specific autoimmune lesions in aged C57BL/6 mice.
We have shown that spontaneously occurring, organ-specific autoimmune lesions develop in aged C57BL/6 mice of both sexes, especially in 24-month-old senescent mice. The inflammatory lesions were found in the multiple organs such as salivary gland, kidney, pancreas, lung, and liver, associated with ageing process. Organ-specific autoimmune lesions first appeared in 6-month-old C57BL/6 mice, and were aggravated with advancing age. In contrast, significant inflammatory changes did not develop in the thyroid, stomach, testis, ovary, and prostate in aged C57BL/6 mice. The incidence and severity of organ-specific autoimmune lesions in this strain of non-autoimmune mice increase with advance of age. The most severely affected lesion was sialadenitis developed in the submandibular salivary gland of aged mice, and a significant difference between male and female mice was noted only in the salivary gland. The infiltrating cells within the lesions of multiple organs consisted mainly of Thy 1.2+ and L3T4+ cells. Autoantibodies were detected in the sera of the mice with each corresponding organ-specific autoimmune lesions.
Aging↗
Differential methylation in steroid 5 alpha-reductase isozyme genes in epididymis, testis, and liver of the adult rat.
DNA methylation has been largely involved in the regulation of tissue-specific gene expression. The aim of the study was to determine the methylation pattern of steroid 5 alpha-reductase genes 1 and 2 in two reproductive tissues (testis and epididymis) and a nonreproductive tissue (liver) that exhibit different contents of steroid 5 alpha-reductase isozymes. These isozymes induce the bioconversion of testosterone to dihydrotestosterone that in mammals is a key molecule for external genitalia development. Genomic DNA from the testis, the epididymis, and the liver from normal adult rats was used to determine cytosine and adenine methylation pattern of steroid 5 alpha-reductase genes 1 and 2 by restriction fragment length polymorphism (RFLP) analysis using restriction enzymes sensitive to adenine (Mbo I and Sau3A I) and cytosine (Hpa II and MSP I) methylation. We also evaluated the expression of both steroid 5 alpha-reductase genes by northern blot. When genomic DNA was digested with Hpa II or Msp I, we found that steroid 5 alpha-reductase gene 2 was less cytosine methylated in the epididymis and in the testis than in the liver. In contrast, when genomic DNA was digested with Mbo I or Sau3A I, we observed that gene 2 was more adenine methylated in the epididymis and in the testis than in the liver. 5 alpha-Reductase gene 1 presented the same adenine- and cytosine-methylation pattern in the studied tissues. We also found a differential expression of steroid 5 alpha-reductase genes. Gene 2 was expressed both in the testis and the epididymis but not in the liver; whereas gene 1 was only expressed in the latter. Our results suggest that the differential methylation pattern in 5 alpha-reductase gene 2 in reproductive and nonreproductive tissues should be involved in the regulation of its expression.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
Impact of ivermectin on the ultrastructure of the testis of Argas (Persicargas) persicus (Ixodoidea: Argasidae).
Mated male Argas persicus were dissected 1 and 2 weeks after feeding on untreated and ivermectin (IVM)-treated pigeons. One week after feeding, testes of untreated ticks were filled with rounded spermatids with subplasmalemmal vesicles and cytoplasmic organelles, but lacking in treated ticks. Two weeks after feeding, testes were crowded with elongated spermatozoa supported by double-walled cisternal tubes. The tubes consisted of two opposite walls, each with outer-fringed processes and inner elongated cisternae. Both were supported with electron dense striated plates in the middle of the spermatozoon. Internally, the cisternal tubes contained mitochondria and vacuoles. The nuclei were elongated dense masses between the tubes and the cell membranes. Subcutaneous inoculation of IVM at the dose 400 microg/kg pigeon resulted in extensive alterations in the testis of A. persicus. IVM prevented the development of new spermatids. There was a break down of cell membranes and cytoplasmic organelles of spermatozoa. Multivesicular bodies and numerous vacuoles were noticed in their cytoplasm. Double membranes of elongated cisternae and striation of electron dense plates became indistinct. IVM caused granulation and vacuolization of the nucleus as well as injury of mitochondrial cristae. The results suggest that IVM may bind to the neurotransmitter or the hormone involved in the process of sperm development or may be toxic to the germinal cells of A. persicus testis.
Animals↗
Sexual development and the effects of active immunization against GnRH in Chinese Tanyang ram lambs.
Tanyang is one of the most important sheep breeds in the northwest of China. However, there is no detailed data on sexual development and timing of puberty/sexual maturity of this breed. This experiment was designed to study the relationships between growth rate and sexual development by measuring body weight, testis diameter, and plasma testosterone concentrations, and observing sexual behavior through puberty from 3 to 8 months old of entire Tanyang ram lambs. At same time, to assess the potential efficacy and welfare benefits of non-surgical castration, the effect of active immunization against gonadotrophin-releasing hormone (GnRH) on sexual development and growth rate on ram lambs was evaluated, and compared with surgically castrated and entire lambs. The results showed that body weight increased at a constant rate from 3 to 8 months old of age. Testis diameter increased rapidly between 3 and 5 months, followed by a period of slow growth. Plasma testosterone concentrations increased sharply from 3 to 6 months of age (P<0.05), after which there were no significant changes from 6 to 8 months of age. Sexual behavior started from 5 months of age. After ram lambs were immunized against GnRH at 3 months of age, there was no increase in testis diameter in the first 4 months after immunization. Plasma testosterone concentrations remained at similar levels to surgically castrated lambs until 6 months of age, and the onset of sexual behavior was delayed, compared with entire ram lambs. GnRH immunization and surgical castration had no significant effect on the body weight by the end of this experiment. These results suggest that 4-5 months of age is a critical period for pubertal changes and testosterone plays an important role in the initiation of puberty and sexual maturity of Tanyang ram lambs in China. In addition, a single shot GnRH immunization at 3 months, acting as an alternative to surgical castration, is a practical method for Chinese Tanyang ram lambs, and provides animal welfare benefits.
Aging↗
Sex determination: a 'window' of DAX1 activity.
Traditionally, DAX1 was considered an 'anti-testis' gene because DAX1 duplications in XY individuals cause male-to-female sex reversal: dosage-sensitive sex reversal (DSS). In DSS, two active DAX1 genes on one X chromosome can abrogate testis formation. By contrast, mutations and deletions of DAX1 cause adrenal hypoplasia congenita (AHC). Although AHC patients develop testes, gonadal defects include disorganized testis cords and hypogonadotropic hypogonadism, which is not completely restored with gonadotropin or androgen therapy. Recent evidence of XY sex reversal in Dax1-deficient mice strongly supports a role for Dax1 as a 'pro-testis' gene. Therefore, perhaps DAX1/Dax1 acts within a 'window' of activity, outside of which testis formation does not occur. Here, we discuss the function and possible mechanisms of DAX1 action in male gonadogenesis.
Animals↗
Familial tumor of the testis.
A survey of the literature since 1928 yields reports on 100 patients with testicular tumor occurring in families. From our own case material we present clinical data on 11 additional patients. Non-twin brothers are most often involved. Presently available data are too limited to assess the impact of a possible genetic disposition on the development of malignoma of the testis. Additional case reports and register studies are needed. Equally undecided is the question if sperm banking of testicular tumor patients prior to therapy carries any genetic risk to the progeny.
Adult↗
Tissue specificity of calspermin: a heat-stable Mr 32,000 calmodulin-binding protein.
We previously reported that rat testis and porcine testis contain a physicochemically indistinguishable Mr 32,000 calmodulin-binding protein, which we named "calspermin." In this study, antiserum against calspermin from porcine testis was raised in a rabbit, and a radioimmunoassay was developed. The antiserum reacted with calspermin from porcine testis but possessed little cross-reactivity against calspermin from rat testis. Among various porcine tissues, this protein was found primarily in testis, sperm, and brain. Its concentration in the cytosol was higher than that in the particular fraction in testis, but the reverse was found in brain. In brain, its concentration was highest in gray matter of cortex and in cerebellum, and became lower in tectum, white matter of cortex, hypothalamus, midbrain, and pons, in this order, and was nondetectable in medulla oblongata.
Animals↗
History, chemistry and pharmacodynamics of anabolic-androgenic steroids.
It had been known for centuries that castration resulted in the loss of certain secondary male sex characteristics. The first inkling as to the cause of these changes were provided in 1849 by a prevention of the regression of the comb and wattles of capons by implantation of testis into the abdominal cavity of the castrated rooster. The results were correctly interpreted that the testis secreted a substance into the blood to regulate the development and maintenance of the male characteristics. The first active extract of testis, however, was not prepared until 1927. Shortly thereafter (1929), a similar type of activity was found in men's urine which was followed (1931) by the isolation of a pure substance, androsterone. A substance with the properties of the testis extract was quickly (1935) synthesized and proved to be identical to a pure substance, testosterone, obtained almost simultaneously from testis extract. Testosterone influences the growth, development, and function of practically every organ in the body. The chemically and endogenously modified steroids do not have parallel effects on the different biological properties of testosterone. Furthermore animal species and dose of steroid affect the response of the different organs. Many chemically modified steroids and some endogenous steroids of both the C19 and C21 series exhibit definite separation of undesirable biological effects.
Anabolic Agents↗
[Sex hormone changes during the prepubertal and pubertal development of healthy boy].
The size of testis, testosterone, LH, FSH were measured in 463 healthy boys, ages 5-18 years old. Our results showed that the values of the developmental indices increased with the age, and abruptly elevated at 13 years old indicating the beginning of puberty. At 17, all has indices had achieved the level of adulthood and did not further increase. It suggested the maturity of sex development at 17. The linear correlation analysis revealed a positive correlation between LH, FSH and testosterone (P less than 0.001, P less than 0.05-0.01, separately). The kinetic curves of LH and testosterone were also similar. The rise of LH preceded one age group than that of testosterone. The correlation between LH, FSH and testis size were positive correlation (before 14, P less than 0.001, P less than 0.01, separately; after 14, no significant difference in P values) and LH was positive correlation since 5 years old, but FSH was positive correlation since 7 years old. These finding suggest that the prepubertal testicular enlargement is primarily due to the action of LH and afterwards, FSH and testosterone combined with LH also contribute to the enlargement of testes. The clinical significance of sex hormone measurement was discussed.
Adolescent↗
[Autoimmune nature of spermatogenesis disorders in varicocele models in rats].
Partial decrease of venous drainage from the left testis in male rats induced development of destructive changes in the seminiferous epithelium at the site of operation and in the contralateral organ. Spermatogenesis disturbances in the rat testes (focal desquamation of seminiferous epithelium, disorganization and degeneration of germ cells, devastation of seminiferous tubules) resembles the lesion in men with varicocele. These data permit to consider the results of present experiment as varicocele modelling. Disturbance of permeability and of the fine blood-testis barrier structure in both testes was observed in experimental rats; the picture of morphological changes was similar to that of autoimmune orchitis; lymphocytes sensitized to spermatozoa antigens were revealed in the lymphoid organs of experimental rats. The results obtained permit to suggest the involvement of immunological mechanisms in the development of pathological changes in the testes affected with varicocele.
Animals↗
Viability under the testis capsule of inner cell masses isolated from TOr/TOr mouse embryos.
Single inner cell masses (ICM) isolated by immunosurgery from late blastocysts were able to develop into benign teratomas under the testis capsule after 1 month with a frequency of 76%. This technique was used to examine viability and developmental potency of embryos homozygous for the TOr mutation. The number of teratomas formed by the ICMs derived from TOr/+ X TOr/+ crosses was consistent with what is expected if TOr/TOr ICMs did not produce them. After ectopic culture for a short period, presumed TOr/TOr ICMs gave rise to abnormal spherical structures resembling embryonic parts of the mutant embryos at the egg cylinder stage. These results suggest that TOr/TOr ICMs have greatly decreased competency for developmental potency.
Animals↗
A genuine organ specific alcohol dehydrogenase from hamster testes: isolation, characterization and developmental changes.
Testes of golden hamsters (Mesocricetus auratus) contain a unique form of alcohol dehydrogenase. The enzyme purified to homogeneity is a dimer composed of two identical 41000 dalton subunits and was inhibited by 4-methylpyrazole and 1, 10-phenanthroline. The enzyme prefers primary over secondary alcohol substrates and oxidizes vitamin A (retinol) most efficiently. Its activity in the testis increases during the prepubertal development and such increase is concomitant with, but preceding slightly, the increase in testicular weight and plasma testosterone. These results may implicate the involvement of this enzyme in the development of male hamsters' reproductive system.
Aging↗
[A case of malignant mesothelioma associated intrascrotal mass].
A 70-year-old male was hospitalized for right scrotal mass without pain in October 1991. Right orchiectomy was performed under a diagnosis of right epididymal tumor. Histopathological diagnosis was testicular adenomatoid tumor. In June 1992, he was admitted with a mass in the right inguinal region and a tumor was resected. Histopathological diagnosis was malignant testicular mesothelioma. Therefore, retroperitoneal lymphadenectomy was performed as additional therapy. One year after surgery he showed signs of recurrence and was admitted for treatment and further examination. Computed tomography demonstrated right inguinal and femoral mass. Thus he underwent total penectomy and radical ilioinguinal lymphadenectomy under a diagnosis of metastatic and recurrent mesothelioma of the testis. Three months postoperatively he developed a recurrence in the skin and lung field. After combination chemotherapy, the metastatic skin lesion was in remission but the lung lesion did not respond. Metastatic lung tumor grew rapidly and the patient died. The incidence of malignant mesothelioma of the tunica vaginalis testis is rare and 48 cases have been reported in the literature.
Aged↗
Mice with a targeted mutation of patched2 are viable but develop alopecia and epidermal hyperplasia.
Hedgehog (Hh) signaling plays pivotal roles in tissue patterning and development in Drosophila melanogaster and vertebrates. The Patched1 (Ptc1) gene, encoding the Hh receptor, is mutated in nevoid basal cell carcinoma syndrome, a human genetic disorder associated with developmental abnormalities and increased incidences of basal cell carcinoma (BCC) and medulloblastoma (MB). Ptc1 mutations also occur in sporadic forms of BCC and MB. Mutational studies with mice have verified that Ptc1 is a tumor suppressor. We previously identified a second mammalian Patched gene, Ptc2, and demonstrated its distinct expression pattern during embryogenesis, suggesting a unique role in development. Most notably, Ptc2 is expressed in an overlapping pattern with Shh in the epidermal compartment of developing hair follicles and is highly expressed in the developing limb bud, cerebellum, and testis. Here, we describe the generation and phenotypic analysis of Ptc2(tm1/tm1) mice. Our molecular analysis suggests that Ptc2(tm1) likely represents a hypomorphic allele. Despite the dynamic expression of Ptc2 during embryogenesis, Ptc2(tm1/tm1) mice are viable, fertile, and apparently normal. Interestingly, adult Ptc2(tm1/tm1) male animals develop skin lesions consisting of alopecia, ulceration, and epidermal hyperplasia. While functional compensation by Ptc1 might account for the lack of a strong mutant phenotype in Ptc2-deficient mice, our results suggest that normal Ptc2 function is required for adult skin homeostasis.
Alopecia↗