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At least 325 records · Page 18Linked to original sources

PubMed1995

Thyroid hormone receptor beta mRNA expression in Sertoli cells isolated from prepubertal testis.

A polymerase chain reaction (PCR)-based assay was used to evaluate the expression of thyroid hormone receptor beta mRNA in Sertoli cells isolated from both prepubertal rat and piglet testes. The expression of an mRNA coding for the functional thyroid hormone receptor beta isoform, as established by the PCR assay, agrees with the presence of specific tri-iodothyronine (T3) -binding sites in the Sertoli cell nuclei of both species, as previously evaluated by displacement analysis. The results ratify the existence of a functional T3 receptor in the prepubertal testis and confirm the Sertoli cell as a specific target for thyroid hormone action on the developing testis.

Animals↗

PubMed2000

Temperature-dependent sex determination in the American alligator: expression of SF1, WT1 and DAX1 during gonadogenesis.

Sex determination in mammals and birds is chromosomal, while in many reptiles sex determination is temperature dependent. Morphological development of the gonads in these systems is conserved, suggesting that many of the genes involved in gonad development are also conserved. The genes SF1, WT1 and DAX1 play various roles in the mammalian testis-determining pathway. SF1 and WT1 are thought to interact to cause male-specific gene expression during testis development, while DAX1 is believed to inhibit this male-specific gene expression. We have cloned SF1 and DAX1 from the American alligator, a species with temperature-dependent sex determination (TSD). SF1, DAX1 and WT1 are expressed in the urogenital system/gonad throughout the period of alligator gonadogenesis which is temperature sensitive. SF1 appears to be expressed at a higher level in females than in males. This SF1 expression pattern is concordant with the observed pattern during chicken gonadogenesis, but opposite to that observed during mouse gonadogenesis. Although the observed sexual dimorphism of gonadal SF1 expression in alligators and chickens is opposite that observed in the mouse, it is probable that SF1 is involved in control of gonadal steroidogenesis in all these vertebrates. DAX1 and WT1 are both expressed during stages 22-25 of both males and females. However, there appear to be no sex differences in the expression patterns of these genes. We conclude that DAX1, WT1 and SF1 may be involved in gonadal development of the alligator. These genes may form part of a gonadal-development pathway which has been conserved through vertebrate evolution.

Alligators and Crocodiles↗

PubMed2004

Stimulation of TM3 Leydig cell proliferation via GABA(A) receptors: a new role for testicular GABA.

The neurotransmitter gamma-aminobutyric acid (GABA) and subtypes of GABA receptors were recently identified in adult testes. Since adult Leydig cells possess both the GABA biosynthetic enzyme glutamate decarboxylase (GAD), as well as GABA(A) and GABA(B) receptors, it is possible that GABA may act as auto-/paracrine molecule to regulate Leydig cell function. The present study was aimed to examine effects of GABA, which may include trophic action. This assumption is based on reports pinpointing GABA as regulator of proliferation and differentiation of developing neurons via GABA(A) receptors. Assuming such a role for the developing testis, we studied whether GABA synthesis and GABA receptors are already present in the postnatal testis, where fetal Leydig cells and, to a much greater extend, cells of the adult Leydig cell lineage proliferate. Immunohistochemistry, RT-PCR, Western blotting and a radioactive enzymatic GAD assay evidenced that fetal Leydig cells of five-six days old rats possess active GAD protein, and that both fetal Leydig cells and cells of the adult Leydig cell lineage possess GABA(A) receptor subunits. TM3 cells, a proliferating mouse Leydig cell line, which we showed to possess GABA(A) receptor subunits by RT-PCR, served to study effects of GABA on proliferation. Using a colorimetric proliferation assay and Western Blotting for proliferating cell nuclear antigen (PCNA) we demonstrated that GABA or the GABA(A) agonist isoguvacine significantly increased TM3 cell number and PCNA content in TM3 cells. These effects were blocked by the GABA(A) antagonist bicuculline, implying a role for GABA(A) receptors. In conclusion, GABA increases proliferation of TM3 Leydig cells via GABA(A) receptor activation and proliferating Leydig cells in the postnatal rodent testis bear a GABAergic system. Thus testicular GABA may play an as yet unrecognized role in the development of Leydig cells during the differentiation of the testicular interstitial compartment.

Animals↗

PubMed1991

Cell-cell interactions and the regulation of testis function.

Regulatory interactions have been shown to occur between all the testicular cell types considered. The paracrine factors mediating these interactions generally influence either cellular growth or differentiation. The regulation of cellular growth is essential in the developing testis and is required for the maintenance of spermatogenesis in the adult testis. The rapid rate of germinal cell proliferation and the continuous but slowed growth of the peritubular cells and Leydig cells requires the presence of specific growth factors in the adult. Therefore, cell-cell interactions have evolved that involve growth factors such as IGF, TGF-alpha, TGF-beta and NGF. Other growth factors such as FGF or less characterized components like the seminiferous growth factor (SGF) also may be involved in the paracrine regulation of testis cell growth. An alternate cellular parameter to cell growth to consider is the regulation of cellular function and differentiation. A number of endocrine agents and locally produced paracrine factors have been shown to control and maintain testis cell function and differentiation. Cell-cell interactions mediated by factors such as androgens, POMC peptides, and PModS are all primarily directed at the regulation of cellular differentiation. Therefore, the agents which mediate cell-cell interactions in the testis can generally be categorized into factors that regulate cell growth or those which influence cellular differentiation. The specific cell-cell interactions identified will likely be the first of a large number of cellular interactions yet to be investigated. Although a number of potentially important cell-cell interactions have been identified, future research will require the elucidation of the in vivo physiological significance of these interactions. The existence of different cell types and potential cell-cell interactions in a tissue implies that the actions of an endocrine agent on a tissue will not simply involve a single hormone and single cell. The endocrine regulation of testis function will have effects on cell-cell interactions and be affected by local cell-cell interactions. The ability of LH to influence Leydig cell androgen production promotes a cascade of interactions mediated through several cell types to maintain the process of spermatogenesis. FSH actions on Sertoli cells also promote cell-cell interactions that influence germinal cell development, peritubular myoid cell differentiation and Leydig cell function. Therefore, elucidation of the endocrine regulation of testis function requires an understanding of the local cell-cell interactions in the testis.

Animals↗

PubMed2006

Screening for Y microdeletions in men with testicular cancer and undescended testis.

PURPOSE: To investigate a possible association between testicular cancer or undescended testis and Y microdeletions. METHODS: It was designed as a retrospective clinical study. A total of 225 men with testicular cancer or undescended testis were included to study. Fertile men (n = 200) were investigated as a control. Genomic DNA, which was extracted from blood samples were investigated with a fluorescent multiplex PCR protocol for screening for Y microdeletions. RESULTS: A single STS missing was found in eight men; one from the control group (sY153), seven from the patients group. The positive cases showed a single STS missing of marker sY153 and sY139 in testicular cancer (6/185) and undescended testis (1/40) patients, respectively. CONCLUSIONS: Since no contiguous, real Y microdeletions were found in the study population, it seems that Y microdeletions are not a likely common etiological cause of poor spermatogenesis in testicular cancer and undescended testis. However, it remains to be determined whether men having a single STS missing have a risk of developing testis cancer or having undescended testis.

Adult↗

PubMed1998

Candidate genes in complete and partial XY sex reversal: mutation analysis of SRY, SRY-related genes and FTZ-F1.

The sexual phenotype is established in three steps: (1) the sex chromosome constitution; (2) the differentiation of the gonads; and (3) the response of the internal and external genitalia to the hormones produced by the differentiated gonads. Errors that occur at any of these stages can result in defective sexual differentiation. Therefore the investigation of patients with abnormalities of testis development will help elucidate the mechanisms of sex determination and gonadal differentiation. It was in this way that SRY. the primary testis determining gene was identified. De novo mutations in SRY, result in gonadal dysgenesis by disrupting the DNA-binding activity of the SRY protein. However, only 20% of cases of gonadal dysgenesis, are explained by mutations in SRY or its flanking sequences. Therefore, there are several pieces to this puzzle yet to be discovered and it is hoped that mutation analysis of other genes implicated in gonadal development and differentiation may shed some light on aetiology of gonadal dysgenesis in the remaining 80% of cases.

Animals↗

PubMed1996

Three daily melatonin infusions alter gonadal development but not GnRH neuron number in the medial preoptic area or diagonal band of Broca in Siberian hamsters.

Among juvenile Siberian hamsters reproductive development is associated with an increased number of unipolar GnRH-immunoreactive neurons in the diagonal band of Broca and medial preoptic area. In the present study, GnRH neuron morphology was assessed in male juvenile hamsters which were treated with three daily melatonin (MEL) infusions to initiate or delay gonadal development. Hamsters gestated in short days were transferred to constant light (LL) at day 14 of age and infused on days 18-20 with MEL for 6 h/day. This treatment stimulated testis development compared to that in saline-infused controls. By contrast, testis growth was suppressed by three 12 h MEL infusions in long-day gestated hamsters in LL from day 14. The number of unipolar and bipolar GnRH neuron subtypes was the same irrespective of MEL infusion or preweaning photoperiod. Thus, gonadal response to three MEL infusions is independent of changes in GnRH neuron number.

Animals↗

PubMed2001

Testis determination in mammals: more questions than answers.

In humans, testis development depends on a regulated genetic hierarchy initiated by the Y-linked SRY gene. Failure of testicular determination results in the condition termed 46,XY gonadal dysgenesis (GD). Several components of the testis determining pathway have recently been identified though it has been difficult to articulate a cascade with the known elements of the system. It seems, however, that early gonadal development is the result of a network of interactions instead of the outcome of a linear cascade. Accumulating evidence shows that testis formation in man is sensitive to gene dosage. Haploinsufficiency of SF1, WT1 and SOX9 is responsible for 46,XY gonadal dysgenesis. Besides, data on SRY is consistent with possible dosage anomalies in certain cases of male to female sex reversal. 46,XY GD due to monosomy of distal 9p and 10q might also be associated with an insufficient gene dosage effect. Duplications of the locus DSS can lead to a failure of testicular development and a duplication of the region containing SOX9 has been implicated in XX sex reversal. Transgenic studies in mouse have shown, however, that this mammal is less sensitive to gene dosage than man. Here, we will try to put in place the known pieces of the jigsaw puzzle that is sex determination in mammals, as far as current knowledge obtained from man and animal models allows. We are certain that from this attempt more questions than answers will arise.

Animals↗

PubMed2005

Ontogeny and cellular localization of SRY transcripts in the human testes and its detection in spermatozoa.

The sex-determining region on the Y (SRY) gene is unequivocally designated as the testis-determining factor in mammals; however, its roles beyond sex determination, if any, have been hitherto unknown. To determine whether SRY has any roles beyond sex determination, herein the expression of SRY mRNA was investigated in the midtrimester human fetal, infantile and adult testes as well as in ejaculated spermatozoa. High levels of SRY transcripts were in situ localized to the Sertoli cells of the developing testis at 9 weeks of gestation, and the expression persisted at comparable levels throughout the midtrimester (until 22 weeks) and also in the testis of an infant at 3 months of age. The germ cells and other somatic cells in the testes of fetuses and the infant were negative for SRY expression. The mRNA for SRY was detected in the spermatogenic cells, particularly the spermatogonia and the round spermatids; the expression was negligible in the meiotic stages. A single transcript of approximately 1.2 kb was detected in the adult testes and isolated spermatogonial cells. In the adult testis, in situ hybridization (ISH) studies revealed a switch in the cellular localization of SRY transcripts. SRY transcripts were also demonstrable by RT-PCR of RNA from ejaculated human spermatozoa. ISH revealed the presence of SRY transcripts in the midpiece of 50% of ejaculated sperm. These results suggest that SRY may have extensive roles in male reproductive physiology, such as maturation of fetal testis, spermatogenesis, sperm maturation and early embryonic development.

Adolescent↗

PubMed2007

Germ cell depletion does not alter the morphogenesis of the fetal testis or ovary in the red-eared slider turtle (Trachemys scripta).

In the red-eared slider turtle, Trachemys scripta, both prospective male and female gonads contain primitive cord structures at the time when the gonad first forms. Primordial germ cells arrive in the gonad and accumulate on the coelomic surface. If testis development is initiated, these cords develop further at the same time that germ cells migrate from the coelomic surface and become sequestered in the interior of the cords. In contrast, in the developing ovary germ cells proliferate in a defined cortical domain, while the primitive cords regress and form flattened lacunae in the medulla. Because of their intimate association with these developmental processes, we investigated whether germ cells were required in turtles to establish the morphology of the fetal testis and ovary. We present evidence that normal morphological development of the fetal gonad occurs in both sexes in T. scripta after germ cell depletion, suggesting a conservation of developmental mechanisms across vertebrates.

Animals↗

PubMed2005

Sexually dimorphic expression of the novel germ cell antigen TEX101 during mouse gonad development.

Prospermatogonia, or gonocytes, are the cells that differentiate from primordial germ cells to the first mature type of spermatogonia in the developing testis. Although prospermatogonia play a central role in this stage (i.e., prespermatogenesis), the details regarding their characterization have not been fully elucidated. Recently, we identified a novel mouse testicular germ cell-specific antigen, TES101 reactive protein (TES101RP), in the adult mouse testis. The protein TES101RP is also designated as protein TEX101. In the present study, we investigated the expression of TEX101 on germ cells in developing mouse gonads using histochemical techniques (i.e., immunohistochemistry, BrdU labeling, and TUNEL staining) and reverse transcription-polymerase chain reaction. TEX101 appeared on germ cells in both male and female gonads after the pregonadal period. In the testis, TEX101 was expressed constitutively on surviving prospermatogonia during prespermatogenesis. After the initiation of spermatogenesis, the prospermatogonia differentiated into spermatogonia. TEX101 expression disappeared from the spermatogonia, but reappeared on spermatocytes and spermatids. In the ovary, TEX101 was expressed on germ cells until the start of folliculogenesis; TEX101 was not detected on oocytes that were surrounded by follicular cells. These findings indicate that TEX101 is a specific marker for both male and female germ cells during gonadal development. Because the on and off switching of TEX101 expression in germ cells almost parallels the kinetics of gametogenesis, TEX101 may play an important physiological role in germ cell development.

Animals↗

PubMed2001

From brain determination to testis determination: evolution of the mammalian sex-determining gene.

In mammals, sex is determined by an XY male:XX female sex chromosome system in which a male-dominant gene on the Y chromosome (SRY) determines testis formation. Sex chromosomes evolved from an ordinary autosome pair as the Y chromosome was progressively degraded. The Y chromosome has lost nearly all of its 1500 original genes, and those that survived did so because they evolved a critical role in male determination or differentiation. SRY is typical of Y-borne genes. Comparative gene mapping and sequencing shows that SRY arose quite recently as a degraded version of the SOX3 gene on the X chromosome. SOX3 is expressed predominantly in brain, and so is more likely to be a brain-determining than a testis-determining gene. The male-dominant action of SRYmay be an illusion, as its structure suggests that it works by interfering with the action of a related gene, which in turn inhibits testis development. This hypothesis can give a good account of how a brain-determining gene acquired a role in testis determination via differential dosage of SOX3. SRYhas no central role in sex determination and it can be replaced as a trigger and loft, as have many other Y-borne genes in recent evolutionary history. The absence of SRY in two species of the mole vole (Ellobius) suggests that its useful life is already running out.

Animals↗

PubMed2003

Chemotactic role of neurotropin 3 in the embryonic testis that facilitates male sex determination.

The first morphological event after initiation of male sex determination is seminiferous cord formation in the embryonic testis. Cord formation requires migration of pre-peritubular myoid cells from the adjacent mesonephros. The embryonic Sertoli cells are the first testicular cells to differentiate and have been shown to express neurotropin-3 (NT3), which can act on high-affinity trkC receptors expressed on migrating mesonephros cells. NT3 expression is elevated in the embryonic testis during the time of seminiferous cord formation. A trkC receptor tyrophostin inhibitor, AG879, was found to inhibit seminiferous cord formation and mesonephros cell migration. Beads containing NT3 were found to directly promote mesonephros cell migration into the gonad. Beads containing other growth factors such as epidermal growth factor (EGF) did not influence cell migration. At male sex determination the SRY gene promotes testis development and the expression of downstream sex differentiation genes such as SOX-9. Inhibition of NT3 actions caused a reduction in the expression of SOX-9. Combined observations suggest that when male sex determination is initiated, the developing Sertoli cells express NT3 as a chemotactic agent for migrating mesonephros cells, which are essential to promote embryonic testis cord formation and influence downstream male sex differentiation.

Animals↗

PubMed1996

A male-specific role for SOX9 in vertebrate sex determination.

Mutation analyses of patients with campomelic dysplasia, a bone dysmorphology and XY sex reversal syndrome, indicate that the SRY-related gene SOX9 is involved in both skeletal development and sex determination. To clarify the role SOX9 plays in vertebrate sex determination, we have investigated its expression during gonad development in mouse and chicken embryos. In the mouse, high levels of Sox9 mRNA were found in male (XY) but not female (XX) genital ridges, and were localised to the sex cords of the developing testis. Purified fetal germ cells lacked Sox9 expression, indicating that Sox9 expression is specific to the Sertoli cell lineage. Sex specificity of SOX9 protein expression was confirmed using a polyclonal antiserum. The timing and cell-type specificity of Sox9 expression suggests that Sox9 may be directly regulated by SRY. Male-specific expression of cSOX9 mRNA during the sex determination period was also observed in chicken genital ridges. The conservation of sexually dimorphic expression in two vertebrate classes which have significant differences in their sex determination mechanisms, points to a fundamental role for SOX9 in testis determination in vertebrates. Sox9 expression was maintained in the mouse testis during fetal and adult life, but no expression was seen at any stage by in situ hybridisation in the developing ovary. Male-specific expression was also observed in the cells surrounding the Müllerian ducts and in the epididymis, and expression in both sexes was detected in the developing collecting ducts of the metanephric kidney. These results suggest that SOX9 may have a wider role in the development of the genitourinary system.

Animals↗

PubMed1988

H-Y antigen and sex determination.

The primary development of a male rather than a female gonad in mammals is determined by the presence of a Y chromosome. The other property unique to the Y chromosome is the occurrence of a cell-surface antigen (designated H-Y) which distinguishes male from female. Thus it was determined that male grafts were rejected by otherwise histocompatible females of the same inbred strain and later that H-Y-specific cytolytic T cells were produced by these grafted mice. When it was determined that females grafted with male skin produced antibody defining a serologically detectable male antigen (which may or may not be the same as H-Y), further immunogenetic analysis of this antigenic system became possible in terms of humoral and cellular factors. By using this assay it was demonstrated that the antigen was phylogenetically conserved and that it was expressed in the male mouse embryo as early as the 8-cell stage of development. The notion that H-Y was a single molecular species responsible for triggering the indifferent gonad to differentiate into the testis became a widely accepted hypothesis. In this report the H-Y antigenic system is traced historically from its original description to the role played in testis development. Data are presented which suggest that although H-Y is a male-specific factor and may play a role in male sex determination, it is unlikely that it is the primary inducer of testis differentiation.

Animals↗

PubMed1992

Cloning and mutational analysis of SRY.

A candidate for the male sex-determining gene has recently been isolated. This sex-determining gene (SRY) has been found to be mutated in some individuals with failed testis development, and, in mouse transgenesis, the SRY murine homologue (Sry) causes female-to-male sex reversal. The cloning of SRY should facilitate the characterisation of other genes in the testis-determining pathway and provide information on the mechanism of mammalian developmental decisions.

Animals↗

PubMed1995

Transcriptional regulation of Sertoli cell differentiation (transferrin promoter activation) during testicular development.

Previously testicular peritubular cells have been shown to produce a paracrine factor PModS that promotes Sertoli cell differentiation. This mesenchymal-epithelial cell interaction appears to regulate a number of Sertoli cell differentiated functions including transferrin gene expression. The current study was designed to identify PModS-activated response elements in the transferrin promoter and correlate this with Sertoli cell differentiation that occurs during testis development. The 3-kb transferrin promoter was digested down to approximately 200-bp fragments. Nuclear extracts from Sertoli cells stimulated with PModS were used in gel mobility shift assays. Two promoter regions located at -2.4 kb and -1.9 kb were designated SE1 and SE2. PModS promoted the presence of factors in Sertoli cell nuclear extracts that bind SE1 and SE2. Displacement studies demonstrated that SE1 and SE2 are distinct. A transferrin promoter-reporter construct containing these apparent response elements was activated by PModS, while a minimal transferrin promoter by 600bp excluding SE1 and SE2 was only partially stimulated by PModS. Therefore, PModS appears to in part activate the transferrin promoter through SE1 and/or SE2. Gel shift assays with Sertoli cell nuclear extracts and 20-day-old testis extracts were the same. Interestingly, the nuclear extract from a newborn testis also had a gel shift. Therefore, some of the nuclear factors stimulated by PModS in Sertoli cells and present in mid-pubertal testis were also present at birth upon completion of embryonic development. Previously transferrin expression has been shown to increase significantly at the onset of puberty.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2000

Influence of castration on development of the thymus in neonatal male rats.

The influence of castration on the development of the thymus in neonatal rats was studied to elucidate when after birth the thymus comes under inhibitory regulation by the testis in rats. The relative and absolute weights of the thymus were measured five days after castration these cases. No excessive changes in the weights of the thymus with castration were observed by 31 days after birth. Significant changes in the thymus appeared in the relative weight at 36-day-castration. The absolute weight of the thymus was also significantly increased after 41-day-castration. These findings suggest that in rats the inhibitory regulation of the thymus by testis development does not appear before at least 31 days of age.

Aging↗