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PubMed1979

Orchidopexy in cryptorchidism assessed by clinical, histologic and sperm examinations.

A study was undertaken of 187 patients with unilateral and 41 patients with bilateral cryptorchidism before and after orchidopexy. The mean tubular diameter and the mean tubular fertility index were used as quantitative criteria for assessment of the development of the testes. Before orchidopexy, no significant differences were found between scrotal and cryptorchid testes in patients up to six years of age. Thereafter, the scrotal testis showed marked development in distinction to the cryptorchid testis. After orchidopexy, follow-up examinations were carried out when the patients had reached the age, at least, 18 years. Based on the results of the mean tubular diameter and the mean tubular fertility index, a reasonable degree of fertility would be expected in both the unilateral and the bilateral cryptorchid testes. However, histologic assessment of spermatogenesis in the unilateral cryptorchid testes after orchidopexy showed spermatogenic arrest in 81 per cent and in all patients with bilateral cryptorchid testes after orchidopexy. In the unilateral orchidopexy patients, in distinction to the histologic assesment of spermatogenesis, sperm counts gave good results in 80 per cent; evidently, in these patients, the source of the spermatozoa was the contralateral scrotal testis. That spermatogenesis was defective in 20 per cent of the patients after unilateral orchidopexy suggests and underlying systemic factor affecting both testes.

Adolescent↗
PubMed2003

Dax1 regulates testis cord organization during gonadal differentiation.

Mutations of the DAX1 nuclear receptor gene cause adrenal hypoplasia congenita, an X-linked disorder characterized by adrenal insufficiency and hypogonadotropic hypogonadism. Targeted deletion of Dax1 in mice also reveals primary testicular dysgenesis, which is manifest by obstruction of the rete testis by Sertoli cells and hyperplastic Leydig cells, leading to seminiferous tubule dilation and degeneration of germ cells. Because Dax1 is expressed early in gonadal development, and because Sertoli and Leydig cells are located ectopically in the adult, we hypothesized that these testis abnormalities are the result of an early defect in testis development. In Dax1(-/Y) males, the gonad develops normally until 12.5 dpc. However, by 13.5 dpc, the testis cords are disorganized and incompletely formed in Dax1-deficient mice. The number of germ and Sertoli cells is unchanged, and the expression of Sertoli-specific markers appears to be normal. However, the number of peritubular myoid cells, which normally surround the testis cords, is reduced. BrdU labeling of peritubular myoid cells is low, consistent with decreased proliferation. The basal lamina produced by peritubular myoid and Sertoli cells is disrupted, leading to open and incompletely formed testis cords. Leydig cells, which normally reside in the peritubular space and extend from the coelomic surface to the dorsal surface of the gonad, are restricted to the coelomic surface of Dax1-deficient testis. We conclude that Dax1 plays a crucial role in testis differentiation by regulating the development of peritubular myoid cells and the formation of intact testis cords. The developmental abnormalities in the Dax1-deficient testis lay the foundation for gonadal dysgenesis and infertility in adult mice and, potentially in humans with DAX1 mutations.

Animals↗
PubMed2004

Bilateral testicular teratoma in infancy: report of a rare case treated by testis-sparing surgery.

Testicular tumors are rarely seen in childhood, with germ-cell tumors as the most common type. Teratoma is second only to yolk sac tumor in frequency. Bilateral testicular teratoma is extremely rare. Orchiectomy has been the standard treatment for most tumors of the testes in the past. However, in children, testis-sparing surgery has become the treatment of choice for benign lesions including teratoma. A 10-month-old infant with synchronous bilateral testicular teratomas, one of which was disclosed by ultrasonography, is presented here. While the larger teratoma required unilateral orchiectomy, the smaller tumor in the contralateral testicle was enucleated by testis-sparing surgery. The follow-up at three years was uneventful with normal development of the testis and the boy. Testicular teratoma may reside in both testicles without clinical symptoms. Ultrasound of both testes provides coherent preoperative diagnosis, allowing the surgeon to consider testicular-sparing procedures, thus preventing anorchia in these rare occurrences.

Humans↗
PubMed1984

The retractile testis.

One hundred boys who had a retractile testis on one side were followed up for five years. The position of the retractile testis became higher (in some, it left the scrotum) in 42 boys and the development of this testis was adversely affected in 49. Because of this, regular review of boys with retractile testes should be continued as long as retraction persists.

Child↗
PubMed1988

Developmental and hormonal regulation of cholesterol side chain cleavage cytochrome P-450 in the fetal rabbit testis.

Male sexual differentiation is dependent upon the induction of testosterone synthesis by the fetal testis at a critical phase of development. In the rabbit, testosterone synthesis by the fetal testis is initiated after 17.5-18 days of gestation, reaches peak values by day 21 and subsequently declines. In the present study, we analyzed the specific activity and concentration of immunoreactive cholesterol side chain cleavage cytochrome P-450 (cytochrome P-450scc) in the fetal rabbit testis during development to assess its possible role as a key regulatory enzyme in fetal testicular steroidogenesis. The effects of human chorionic gonadotropin (hCG) and dibutyryl cyclic AMP on the specific activity and synthesis of cytochrome P-450scc in fetal rabbit testes in vitro also were evaluated. We observed that changes in cholesterol side chain cleavage activity paralleled the induction of testosterone synthesis; the specific activity of this enzyme which was approximately equal to 0.25 pmol min-1 mg-1 protein in testes from 19-day fetal rabbits was increased approximately equal to 10-fold in testes of 21-day fetuses and thereafter declined dramatically. Immunoreactive cytochrome P-450scc, which was first detectable in gonads of 19-day fetal rabbits, was induced markedly in 21-day fetal testes, reached maximum levels on day 24 and declined slightly thereafter. Incubation of testes from 19- and 21-day gestational age fetal rabbits with hCG or dibutyryl cyclic AMP for 24 h resulted in an induction of testosterone synthesis, cholesterol side chain cleavage activity and synthesis of cytochrome P-450scc. These findings are suggestive that androgen synthesis by the fetal Leydig cell is mediated by an induction of the synthesis and specific activity of cytochrome P-450scc. In addition, these data support the hypothesis that the developmental changes in the synthesis of cytochrome P-450scc are regulated by fetal gonadotropin and are mediated by cyclic AMP.

Animals↗
PubMed1995

Role of GnRH in the ontogeny and regulation of the fetal hypothalamo-pituitary-gonadal axis in sheep.

Adult reproductive ability is to a large extent determined by the appropriate development of the reproductive axis during fetal life. Studies have investigated the role of the fetal hypothalamus in the ontogeny and regulation of pituitary gonadal function during fetal development in sheep. Using immunocytochemistry, we examined the ontogeny of gonadotroph development in the pituitary of female sheep fetuses. At day 70 of gestation (term = 145 days), only immunopositive LH beta cells were present. The number and intensity of staining of these LH beta cells had increased by day 100 but had declined again by day 130. Immunopositive alpha-subunit and FSH beta cells appeared at day 100 of gestation and had further increased in number and staining intensity by day 130 of gestation. Treatment of fetuses with the GnRH agonist buserelin resulted in desensitization of the fetal pituitary gonadotrophs, inhibition of pituitary LH beta and FSH beta mRNA expression and a reduction in the number of immunopositive gonadotrophin-containing cells. Pulsatile GnRH treatment resulted in pituitary-gonadal activation and an increase in LH, FSH and testosterone secretion in males. Thus, the synthesis and secretion of the gonadotrophins during fetal development is critically dependent on the secretion of GnRH from the fetal hypothalamus. Inhibition of fetal gonadotrophins by buserelin treatment from day 70 of gestation resulted in a 40% reduction in the size of the fetal testis at birth, and there were no effects on the fetal ovaries. This reduction in testis size was due to a 45% reduction in the number of Sertoli cells. However, when buserelin was given between day 70 and day 110 of gestation, there were no effects on testis size or morphological development of the testis, suggesting that gonadotrophins regulate testicular development during a 'critical window' late in gestation. Taken together, these studies provide convincing evidence that GnRH plays a central role in the ontogeny and regulation of pituitary-gonadal function during fetal life.

Animals↗
PubMed1993

Early thyroid hormone treatment in rats increases testis size and germ cell number.

By means of in vivo and in vitro approaches, we studied the effect of thyroid hormone on postnatal development of rat testis. T3 treatment in neonatal rats is associated with an increase of testis size of about 60%, compared to coeval controls. Increased number of both Sertoli and germ cells and enlarged diameter of seminiferous cords were found in hyperplastic testes. In the T3-treated group, TSH serum levels were low and a slight increase of FSH was found. In vitro treatment of neonatal testis fragments by 10(-7) M T3 for 3 days increased the number of gonocytes (P < 0.001 vs control) and decreased the percentage of degenerating germ cells (P < 0.001 vs control). In the adult testis, both in vivo and in vitro treatments with thyroid hormone did not induce morphological modifications, thus demonstrating that the critical window of thyroid hormone effectiveness coincides with the prepuberal period. Since thyroid hormone stimulates Sertoli cells to secrete growth factors and nutrients for germ cell development, we suggest that the increased testicular size and germ cell number following the T3 treatment is mediated by a direct hormonal effect on the somatic cell of the seminiferous epithelium.

Animals↗
PubMed1981

Modulation of steroidogenic activities in testis Leydig cells.

Recent developments in the regulation of testicular Leydig-cell function support the following conclusions. (1) Enzymic activities involved in steroid production in the testis are mainly localized in Leydig cells. The aromatase enzyme complex for oestrogen production appears to be localized in Leydig cells as well as in Sertoli cells. (2) LH- (or hCG-) induced alterations of Leydig cells depend on dose and duration of exposure of the cell to the hormone. Locally produced oestradiol is probably involved in the inhibition of steroidogenesis. (3) The stimulatory action of LH on Leydig cells involves different proteins in concert with the activation of the cleavage activity of mitochondrial cholesterol side-chain. However, most of the functional properties of these proteins are yet unknown. (4) Different populations of Leydig cells are present in the testis. These different cell populations can be characterized by quantitatively and qualitatively different responses to hormones.

Aging↗
PubMed1980

Functional relationships of the mammalian testis and epididymis.

The development of knowledge in four areas of research in male reproductive physiology of particular interest is reviewed. The concept of the blood-testis barrier (BTB), which arose following dye exclusion from the seminiferous tubules, has now been established as the differential transfer from interstitial fluid to tubular and rete testis fluids of molecules of physiological importance. The composition of fluid collected mostly from the rete testis of several species, not only reflects the nature of the barrier, but also the secretory capacity of the Sertoli cell. The functional significance of the transfer of molecules into testicular fluid and the composition of the fluid flowing into the epididymis are discussed. Sertoli cells establish the structural basis of the BTB during puberty and divide the seminiferous epitheliuym into basal and adluminal compartments. The Sertoli cell is the prime target for follicle stimulating hormone (FSH). The responses evoked by FSH are discussed, including special mention of androgen binding protein (ABP) and the protein hormone, 'inhibin', with FSH-suppressing properties. The control of FSH in the lamb is mentioned including new evidence to support a tubular source of a feedback agent with significance during the impuberal stage. Finally, some of the biochemical properties of the epididymis and its fluid contents are reviewed and the epididymal sperm are identified as the site of the antifertility action of the 6-chloro-6-deoxy sugars.

Animals↗
PubMed2001

Developmental and hormonal regulation of type II DNA topoisomerase in rat testis.

Type II DNA topoisomerase (topo II) is required for diverse biological functions including DNA replication, maintenance of genome stability, chromosome segregation and chromosome condensation. While the identity of topo II in rodent testis has been established, the regulation of topo II expression during the development of the postnatal testis and gametogenesis is unclear. Here, we report that rat testis topo II is developmentally and hormonally regulated. Topo IIalpha mRNA levels peaked prior to the onset of puberty, declined sharply thereafter and stabilized in adult testis. In contrast, the topo II enzyme content was lower in prepubertal testis but increased after the onset of puberty. Topo II was expressed in a cell-specific manner within germ cells, being detected only in pachytene spermatocytes. While testosterone markedly increased topo IIalpha mRNA levels in prepubertal testis, continued treatment failed to enhance topo IIalpha mRNA above postpubertal control levels. The extent of topo II activity remained steady regardless of the testosterone-induced increase in topo IIalpha mRNA levels. Inhibition of testosterone function in postpubertal animals by ethanedimethane sulphonate (EDS) and flutamide resulted in a significant decrease in topo IIalpha gene expression and topo II activity. The administration of exogenous testosterone (T) to EDS- and flutamide-treated rats restored topo IIalpha mRNA levels and topo II activity similar to the levels seen in the testis of age-matched control animals. Histochemical analyses of testes indicated that the effect of T on spermatogenesis was separable from its effect on topo IIalpha expression. Our results reveal that testosterone acts as a positive regulator of topo IIalpha gene expression and is required for the maintenance of topo IIalpha expression during the development of the postnatal testis and spermatogenesis.

Animals↗
PubMedDate not supplied

Sequences homologous to ZFY, a candidate human sex-determining gene, are autosomal in marsupials.

Sexual differentiation in placental mammals results from the action of a testis-determining gene encoded by the Y chromosome. This gene causes the indifferent gonad to develop as a testis, thereby initiating a hormonal cascade which produces a male phenotype. Recently, a candidate for the testis-determining gene (ZFY, Y-borne zinc-finger protein) has been cloned. The ZFY probe detects a male-specific (Y-linked) sequence in DNA from a range of eutherian mammals, as well as an X-linked sequence (ZFX) which maps to the human X chromosome. In marsupials it is also the Y chromosome that seems to determine the fate of the gonad, but not all sexual dimorphisms. Using the ZFY probe we find, surprisingly, that the ZFY homologous sequences are not on either the X or the Y chromosome in marsupials, but map to the autosomes. This implies ZFY is not the primary sex-determining gene in marsupials. Either the genetic pathways of sex determination in marsupials and eutherians differ, or they are identical and ZFY is not the primary signal in human sex determination.

Animals↗
PubMed1991

Fine structural characteristics of testicular cord formation in the developing rabbit gonad.

This paper presents morphological (light- and electron-microscopical) evidence for the role of the mesonephros in contributing cells to the differentiating indifferent gonad and, after sexual differentiation, to the testis. A continuous process is revealed during which segregation of cells occurs from the developing and regressing mesonephros. Additionally, the complementary role of the coelomic epithelium in gonadal ridge and testis formation is demonstrated. The differentiation of testicular cords, their remodelling from a primary reticulum, and the composition and further change of the cellular content during the period after sexual differentiation is described using a computer-aided three-dimensional reconstruction system. Apart from these morphogenetic events, cytodifferentiation in the somatic cells of the indifferent gonad and of the early differentiated testis is demonstrated using indirect immunofluorescence in combination with monoclonal antibodies to the intermediate filament proteins keratin 8 and 18 and vimentin. The immunohistochemical results show that different forms of cytodifferentiation coexist among the somatic cells present in the indifferent gonad and in the testis early after sexual differentiation.

Animals↗