SEARCH · PubMed Health

Results for “testis development”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 487 records · Page 27Linked to original sources

PubMed2003

Medaka dmY/dmrt1Y is not the universal primary sex-determining gene in fish.

An outstanding candidate for a primary male-determining gene equivalent to Sry of mammals has been recently described from a non-mammalian vertebrate, the medaka fish (Oryzias latipes). However, the universality of dmY/dmrt1Y as the master sex-determining gene in fish is questionable. Phylogenetic analysis shows that dmY/dmrt1Y is an evolutionarily young Y chromosome-specific duplicate of a gene involved in testis development in vertebrates, and that this duplicate cannot be the primary sex-determining gene in most other fish species. Study of alternative fish models will probably uncover new genetic strategies controlling sexual dimorphism in vertebrates.

Animals↗

PubMed2002

The marsupial model for male phenotypic development.

In all mammals, androgen formed in the developing testes is responsible for the aspects of male development in which the Wolffian ducts, urogenital sinus and urogenital tubercle are transformed into the epididymis/vas deferens, prostate and penis. That these events take place after birth in the marsupial makes it possible to examine male phenotypic development during pouch life. In the tammar wallaby, Macropus eugenii, the testicular androgen 5 alpha-androstane-3 alpha,17 beta-diol (5 alpha-adiol) is formed in the developing testis, is secreted into plasma and has the capacity to virilize female young pouch when administered exogenously. 5 alpha-Adiol is formed by immature testes in many species and appears to act in target tissues once it has been converted to dihydrotestosterone.

Animals↗

PubMedDate not supplied

Testicular microlithiasis: a review and its association with testicular cancer.

Testicular microlithiasis (TM) is an entity of unknown etiology that results in the formation of intratubular calcifications. It is of concern to the urologist because of its possible association with intratubular germ cell neoplasia and testicular germ cell cancer. Although commonly present in patients with germ cell tumors, there appears to be no definitive association with TM and cancer. Therefore, follow-up at this time should be dictated based on risk factors for developing testis cancer more than on the presence of TM.

Humans↗

PubMed2004

Regulation of human SRY subcellular distribution by its acetylation/deacetylation.

SRY, a Y chromosome-encoded DNA-binding protein, is required for testis organogenesis in mammals. Expression of the SRY gene in the genital ridge is followed by diverse early cell events leading to Sertoli cell determination/differentiation and subsequent sex cord formation. Little is known about SRY regulation and its mode of action during testis development, and direct gene targets for SRY are still lacking. In this study, we demonstrate that interaction of the human SRY with histone acetyltransferase p300 induces the acetylation of SRY both in vitro and in vivo at a single conserved lysine residue. We show that acetylation participates in the nuclear localisation of SRY by increasing SRY interaction with importin beta, while specific deacetylation by HDAC3 induces a cytoplasmic delocalisation of SRY. Finally, by analysing p300 and HDAC3 expression profiles during both human or mouse gonadal development, we suggest that acetylation and deacetylation of SRY may be important mechanisms for regulating SRY activity during mammalian sex determination.

Acetylation↗

PubMed1993

Leydig cell neoplasia in a patient with Reifenstein syndrome.

We present the rare coincidence of a Leydig cell tumor in both testicles of a patient with partial androgen insensitivity syndrome (PAIS). The clinical picture with perineoscrotal hypospadia, micropenis, gynecomastia and delayed puberty and the serum hormone levels with elevated concentrations of testosterone, luteinising hormone (LH) and follicle-stimulating hormone were entirely consistent with PAIS. Ultimately, the diagnosis was confirmed by determination of genital skin fibroblast androgen receptor binding capacity for 5 beta-dihydrotestosterone, which demonstrated a qualitatively abnormal androgen receptor. At 44 years of age, a nodule in the left testis led to orchidectomy. At that time, the right testis was inconspicuous sonographically. But 3 years later the right testis developed nodules and was removed. Review of testicular histology revealed the presence of Leydig cell hyperplasia (LCH), multifocal nodular hyperplasia and Leydig cell neoplasia (LCN) in both testes. Many micronodules of Leydig cells in transition from hyperplasia to neoplasia were also identified. The simultaneous development of histologically identical nodes of LCN independently from each other and a different sites of both tests indicates the presence of a tumorigenic factor acting on the Leydig cells. Furthermore, the observation of multiple foci of cells in all stages of transition from hyperplasia to neoplasia demonstrates the persistent process of transformation. We speculate, that in this patient the grossly elevated LH levels present over 30 years have enhanced, if not provoked, the formation of LCN. In addition, the defective androgen receptor might have prevented suppressive effects of androgens on the Leydig cells.

Disorders of Sex Development↗

PubMed1995

The genes for a spliceosome protein (SAP62) and the anti-Müllerian hormone (AMH) are contiguous.

During an investigation of the regulatory potential of a region 5' of the mouse anti-müllerian hormone (Amh) gene, we identified a region of homology with the known cDNA sequence of a human spliceosome gene (SAP62). In mouse, the Sap62 termination codon (TGA) is just 434 bp 5' of the Amh start of translation (ATG); in the human the equivalent distance is 789 bp. RNase protection analysis shows the majority of Sap62 transcripts use an uncommon polyadenylation signal (ATTAAA) lying in the intragenic region, 87 bp 3' of the TGA. This analysis also shows that Sap62 is transcribed in all tissues examined, whereas specific Amh transcription initiating 10 bp 5' of the ATG is limited to the developing testis of the fetus from 11.5 days post coitum and in the ovary from 3 days post partum. However, in all tissues a significant number of Sap62 transcripts fail to polyadenylate in the intragenic region and continue through the Amh locus. This implies that the Amh locus is in an open chromatin state in all tissues despite a requirement for precise regulation. Human SAP62 can now be mapped to HSA19p and mouse Sap62 to MMU10.

Amino Acid Sequence↗

PubMed2003

Loss of DNA-dependent dimerization of the transcription factor SOX9 as a cause for campomelic dysplasia.

Campomelic dysplasia (CD) is a semilethal osteochondrodysplasia, characterized by skeletal anomalies that include bending of the long bones, and by XY sex reversal. CD results from haploinsufficiency for the transcription factor SOX9, a key regulator at various steps of cartilage differentiation and of early testis development. Two functional domains are so far recognized for SOX9, a high-mobility group (HMG) DNA-binding domain and a C-terminal transactivation domain. We present two CD patients with de novo mutations in a conserved region preceding the HMG domain. A long-term survivor with the acampomelic form of CD has an A76E amino acid substitution, while a severely affected CD patient had an in-frame deletion of amino acid residues 66-75. The conserved domain has been shown to function in the related transcription factor SOX10 as a DNA-dependent dimerization domain. We show that, like SOX10, SOX9 also binds cooperatively as a dimer to response elements in regulatory regions of some target genes such as the cartilage genes Col11a2 and CD-Rap. Dimerization and the resulting capacity to activate promoters via dimeric binding sites is lost in both mutant SOX9 proteins while other features involved in SOX9 function remained unaltered. These findings establish the dimerization domain as the third domain essential for SOX9 function during chondrogenesis.

Amino Acid Sequence↗

PubMed2003

Cellular and subcellular localization of the ARPKD protein; fibrocystin is expressed on primary cilia.

Autosomal recessive polycystic kidney disease (ARPKD) is an infantile form of PKD characterized by fusiform dilation of collecting ducts and congenital hepatic fibrosis. The ARPKD gene, PKHD1, is large (approximately 470 kb; 67 exons) with a 12222 bp longest open reading frame, although multiple different splice forms may be generated. The predicted full-length ARPKD protein, fibrocystin, is membrane bound with 4074 amino acids (447 kDa molecular weight). To characterize the pattern of fibrocystin expression we have generated four monoclonal antibodies (mAb) to the cytoplasmic tail of the protein. Western analysis of human kidney membrane protein showed an identical pattern with each mAb; a strongly expressing large product (>450 kDa), consistent with the predicted protein size, and a weaker approximately 220 kDa band. The same large product was detected in rat and mouse kidney with lower level expression in liver. To further show that these mAbs recognize fibrocystin, tissue from ARPKD patients was analyzed and no fibrocystin products were detected. Immunohistochemical analysis of the developing kidney showed expression in the branching ureteric bud and collecting ducts, expression that persisted into adulthood. Biliary duct staining was found in the liver, plus staining in the pancreas and developing testis. Immunofluorescence analysis of MDCK cells showed a major site of expression in the primary cilia. Recent studies have associated the disease protein in various human and animal forms of PKD with cilia. The localization of fibrocystin to cilia further strengthens that correlation and indicates that the primary defect in ARPKD may be linked to ciliary dysfunction.

Animals↗

PubMed1999

Expression specificity of the mouse exonuclease 1 (mExo1) gene.

Genetic recombination involves either the homo-logous exchange of nearly identical chromosome regions or the direct alignment, annealing and ligation of processed DNA ends. These mechanisms are involved in repairing potentially lethal or mutagenic DNA damage and generating genetic diversity within the meiotic cell population and antibody repertoire. We report here the identification of a mouse gene, termed mExo1 for mouse exonuclease 1, which encodes a approximately 92 kDa protein that shares homology to proteins of the RAD2 nuclease family, most notably human 5' to 3' exonuclease Hex1/hExo1, yeast exonuclease 1 (Exo1) proteins and Drosophila melanogaster Tosca. The mExo1 gene maps to distal chromosome 1, consistent with the recent mapping of the orthologous HEX1 / hEXO1 gene to chromosome 1q42-q43. mExo1 is expressed prominently in testis, an area of active homologous recombination, and spleen, a prominent lymphoid tissue. An increased level of mExo1 mRNA was observed during a stage of testis development where cells that are actively involved in meiotic recombination arise first and represent a significant proportion of the germ cell population. Comparative evaluation of the expression patterns of the human and mouse genes, combined with previous biochemical and yeast genetic studies, indicate that the Exo1-like proteins are important contributors to chromosome processing during mammalian DNA repair and recombination.

Amino Acid Sequence↗

PubMed2004

Peroxisome proliferator-activated receptors: mediators of phthalate ester-induced effects in the male reproductive tract?

Many phthalate ester plasticizers are classified as peroxisome proliferators (PP), a large group of industrial and pharmaceutical chemicals. Like PP, exposure to some phthalates increases hepatocyte peroxisome and cellular proliferation, as well as the incidence of hepatocellular adenomas in mice and rats. Most effects of PP are mediated by three nuclear receptors called peroxisome proliferator-activated receptors (PPARalpha,beta,gamma). An obligate role for PPARalpha in PP-induced events leading to liver cancer is well-established. Exposure of rats in utero or in the neonate to a subset of phthalate esters causes profound, sometimes irreversible malformations in the male reproductive tract. We review here the data that supports or discounts roles for PPARs in phthalate-induced testis toxicity including (1) toxic effects of phthalates on the male reproductive tract, (2) expression of PPARs in the testis, (3) activation of PPARs by phthalates, (4) role of PPARalpha in testis toxicity, (5) gene targets of phthalates involved in steroid biosynthesis and catabolism, and (6) interactions between PPARs and other nuclear receptors that play roles in testis development and homeostasis. Critical research needs are identified that will help determine the significance of PPARs in phthalate-induced effects in the rat male reproductive tract and the relevance of toxicity to humans.

Animals↗

PubMed1995

Hormonal regulation of urokinase- and tissue- type plasminogen activator in rat Sertoli cells.

Tissue type (t) and urokinase type (u) plasminogen activators (PA) have been shown to be secreted by Sertoli cells in the seminiferous tubules in a cyclic fashion and to be dependent upon hormonal stimulation or the presence of adjacent spermatogenic cells. Furthermore, in cultured Sertoli cells, tPA has been shown to respond to FSH induction whereas uPA appears to be nonresponsive to gonadotropins. In the present study we analyzed the production of PA by Sertoli cells and regulation of this production by FSH during puberty. Cultured Sertoli cells under basal conditions secreted predominantly uPA. This production was high in 10-day-old animals and gradually decreased in older animals. The treatment of cultures with FSH or dibutyl cAMP induced production of tPA by Sertoli cells but at the same time produced a decrease in uPA activity. Northern blot analysis revealed that the control of PA synthesis is at the steady-state level of their mRNAs. Moreover, the use of cycloheximide, a protein synthesis inhibitor, showed that while tPA stimulation did not require intermediary protein synthesis, the decrease in uPA production was dependent upon protein synthesis. The differences in PA production by Sertoli cells obtained after FSH stimulation could explain the cyclic production of the two enzymes during the spermatogenic cycle and reinforce the hypothesis that different roles are played by the two enzymes in the several events occurring in testis development.

1-Methyl-3-isobutylxanthine↗

PubMed1999

Fertility of Y(TIR).B6 sex-reversal females with XX orthotopic ovarian transplants.

When the Y chromosome of Mus musculus domesticus (Y(TIR)) was introduced onto the C57BL/6J (B6) mouse background, testis development was impaired and half of the XY progeny (Y(TIR).B6) developed a female phenotype. Y(TIR).B6 fetal ovaries showed massive death of medullary oocytes and, after birth, produced abnormal levels of steroid hormones, exhibited irregular estrous cycles, and failed to become fertile. In this study we examined whether alterations during perinatal development observed in Y(TIR).B6 ovaries permanently impaired the establishment of the hypothalamus-pituitary-ovary axis (HPOa). B6 fetal and postnatal ovaries at different stages (fetal, infantile, or adult) were transplanted orthotopically (to the ovarian bursa) to either ovariectomized B6 normal females or Y(TIR).B6 sex-reversal females. Percentage of pregnancy, litter size, and capacity to feed pups were recorded. Reciprocally, XY(TIR).B6 ovaries were orthotopically transplanted into B6 females. After crossing with fertile males, several Y(TIR).B6 sex-reversal females with B6 ovarian transplants at all ages became pregnant, had offspring, and fed their pups. On the other hand, none of the B6 female hosts with XY(TIR) ovaries became pregnant. Results demonstrated that Y(TIR).B6 sex-reversal females maintain a functional HPOa and that their failure to reproduce is primarily due to an ovarian defect.

Animals↗

PubMed1995

Germ cell cancer of the testes.

New insights into the etiology and specifically the role of atrophy in generating increased gonadotropin drive have come from a case-control study of 794 patients. This study demonstrated possible evidence for trauma and infection-related atrophy, although of most interest from the point of view of the gonadotropin drive hypothesis is the observation that, as with breast cancer, exercise may reduce the risk and early onset of puberty may increase the risk. The value of self-examination education as a way of reducing delay in diagnosis was debated from the viewpoint of general practice. This provided a timely reminder that, in a rare tumor with a more than 95% cure rate, such education might generate more anxiety about the disease than it would early diagnoses. The total absence of carcinoma in situ at the time of orchidectomy in a series of cryptorchidic patients who subsequently developed testis cancer after orchidopexy provides a good reason for not performing a biopsy. The late nongerm cancers at 15 to 20 years after radiation therapy have provoked reexamination of priorities for stage I seminoma. New data from two centers that have used a single course of carboplatin as adjuvant therapy with no relapses in 104 patients are of considerable interest in providing an alternative to radiation therapy.

Germinoma↗

PubMed1981

Age dependent changes in FSH responsive adenylyl cyclase and FSH binding in rat testes.

FSH responsive adenylyl cyclase (AC) activities were examined in both homogenates and membrane particles from 9-71 days old rat testes, and FSH binding was determined in membrane particles from the same animals. FSH responsive AC was measured in the presence of either GTP (0.04 mM) or the non-metabolizable GTP analogue, GMP-P(NH)P (0.04 mM). From days 9 and 11 there was a gradual decrease in both basal and FSH stimulated AC activities and a very similar decrease in FSH binding. The relative stimulation by FSH, however, was fairly constant (2-3 fold stimulation). The excellent correlation between specific FSH binding and FSH responsive AC activities during sexual maturation does not support the notion that uncoupling of the FSH receptors from the AC is a primary reason for the attenuated FSH response during pubertal development. The age dependent decrease in both basal and FSH stimulated AC activities during sexual maturation is a reflection of the relative increase in germ cells (containing no FSH receptors and FSH responsive AC). The LH/hCG responsive AC in membrane particles from the same ages showed an age dependent increase in both absolute activities and relative responses, probably indicating the increased number of Leydig cells in the developing testis.

Adenylyl Cyclases↗

PubMed1993

The effect of two-stage orchiopexy on testicular growth.

Testicular growth was measured in 33 males who had undergone 2 orchiopexies on the developing testis. Multiple surgery on the abdominal or canalicular testis was associated with a high rate of testicular atrophy (40%) and a 46% decrease in testicular volume. A similar decrease (43%) in testicular volume was noted in those patients with an infracanalicular testis but no testis atrophied in this group. The results suggest that primary orchiectomy be considered in the high testis provided the contralateral testis is normal, or alternatively a Fowler-Stephens or microvascular transplant if it is not. Patients with an infracanalicular testis may undergo a careful second-stage orchiopexy. All patients with retarded testicular growth should perform routine self-examination.

Atrophy↗

PubMed2002

Germline stem cell transplantation and transgenesis.

The recently developed testis cell transplantation method provides a powerful approach to studying the biology of the male germline stem cell and its microenvironment, the stem cell niche. The technique also is being used to examine spermatogenic defects, correct male infertility, and generate transgenic animals.

Animals↗

PubMed1991

A DNA polymorphism from five inbred strains of the mouse identifies a functional class of domesticus-type Y chromosome that produces the same phenotypic distribution of gonadal hermaphrodites.

The wild-derived CLA inbred strain of the house mouse contains a domesticus-type Y chromosome that lacks a 2.3-kb TaqI band with fragment 1 of the AC11 probe. The CLA Y chromosome also causes a low frequency of XY gonadal hermaphrodites when backcrossed to the C57BL/6J strain (F. G. Biddle and Y. Nishioka, 1988. Genome, 30:870-878). A similar domesticus-type Y chromosome, lacking the 2.3-kb TaqI band has now been found in the four historical inbred strains AKR/J, MA/MyJ, PL/J, and RF/J. When backcrossed to C57BL/6J, these four Y chromosomes cause low frequencies of gonadal hermaphrodites similar to the CLA Y and phenotypic distribution of types of gonad are indistinguishable from that with the CLA Y. The absence of the 2.3-kb TaqI band appears to be a polymorphism among domesticus-type Y chromosomes that identifies one of the three functional classes that, so far, can be distinguished only by their effects on testis differentiation in backcross test fetuses with the C57BL/6J strain. Three other historical inbred strains, BUB/BnJ, ST/bJ, and SWR/J, with a domesticus-type Y chromosome but containing the 2.3-kb TaqI band, were also assayed. They permit normal testis development in backcross test fetuses with C57BL/6J.

Animals↗

PubMed2002

Z and W chromosomes of chickens: studies on their gene functions in sex determination and sex differentiation.

Since the discovery of SRY/SRY as a testis-determining gene on the mammalian Y chromosome in 1990, extensive studies have been carried out on the immediate target of SRY/SRY and genes functioning in the course of testis development. Comparative studies in non-mammalian vertebrates including birds have failed to find a gene equivalent to SRY/SRY, whereas they have suggested that most of the downstream factors found in mammals including SOX9 are also involved in the process of gonadal differentiation. Although a gene whose function is to trigger the cascade of gene expression toward gonadal differentiation has not been identified yet on either W or Z chromosomes of birds, a few interesting genes have been found recently on the sex chromosomes of chickens and their possible roles in sex determination or sex differentiation are being investigated. It is the purpose of this review to summarize the present knowledge of these sex chromosome-linked genes in chickens and to give perspectives and point out questions concerning the mechanisms of avian sex determination.

Animals↗