Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE57924 | GEO | 2014/07/02
SECONDARY ACCESSION(S): PRJNA248430
REPOSITORIES: GEO
Similar Datasets
Project description:This study was designed to provide additional insight into testicular hormone production and responsiveness in the orl strain and complement ongoing efforts to characterize the genetic basis of cryptorchidism in this isolated rat colony. Gubernacula were harvested from Long Evans and ORL rat embryos at gestational day 17 and 19. RNA was purified from litter-based organ pools. 26 RNA samples were processed and hybridized to GeneChips. Please note that a mix-up of the samples gubernaculum-GD19-a and -b appears to have occurred as data from these samples clustered with the opposite strain than expected in hierarchical clustering analysis. Thus the strain information was annotated as 'unknown'.
2014-07-02 | E-GEOD-57924 | biostudies-arrayexpress
Project description:Cryptorchidism is the most common congenital defect in children's genitourinary system. It is one of the risk factors for male infertility and testicular tumors. The occurrence of cryptorchidism is closely related to many factors, and the alteration of genes plays an important role in the occurrence of cryptorchidism. A large number of studies have confirmed that the formation of cryptorchidism is related to the differential expression of genes. Therefore, exploring new differential expression genes of cryptorchidism from the transcriptome level and studying the relationship between susceptibility genes and children with cryptorchidism can provide a new direction for studying the pathogenesis of cryptorchidism.
2020-04-23 | GSE149084 | GEO
Project description:Cryptorchidism, or undescended testis, is a common male genital anomaly of unclear etiology. Hormonal stimulation of the developing fetal gubernaculum by testicular androgens and insulin-like 3 (INSL3) is required for testicular descent. In studies of the orl fetal rat, one of several reported strains with inherited cryptorchidism, we studied hormone levels, gene expression in intact and hormone-stimulated gubernaculum, and imaging of the developing cremaster muscle facilitated by a tissue clearing protocol to further characterize development of the orl gubernaculum. Abnormal localization of the inverted gubernaculum was visible soon after birth. In the orl fetus, testicular testosterone, gubernacular androgen-responsive transcript levels, and muscle-specific gene expression were reduced. However, the in vitro transcriptional response of the orl gubernaculum to androgen was largely comparable to wild type (wt). In contrast, increases in serum INSL3, gubernacular INSL3-responsive transcript levels, expression of the INSL3 receptor, Rxfp2, and the response of the orl gubernaculum to INSL3 in vitro all suggest enhanced activation of INSL3/RXFP2 signaling in the orl rat. However, DNA sequence analysis did not identify functional variants in orl Insl3. Finally, combined analysis of the present and previous studies of the orl transcriptome confirmed altered expression of muscle and cellular motility genes, and whole mount imaging revealed aberrant muscle pattern formation in the orl fetal gubernaculum. The nature and prevalence of developmental muscle defects in the orl gubernaculum are consistent with the cryptorchid phenotype in this strain. These data suggest impaired androgen and enhanced INSL3 signaling in the orl fetus accompanied by defective cremaster muscle development.
| S-EPMC4435416 | biostudies-literature
Project description:Despite timely and successful surgery, 32% of patients with bilateral and 10% with unilateral cryptorchidism will develop azoospermia. Cryptorchid boys at risk of azoospermia display a typical testicular histology of impaired mini-puberty at the time of the orchidopexy. During mini-puberty increased gonadotropin and testosterone secretion stimulate transformation of gonocytes into Ad spermatogonia. In azoospermia risk group this transformation is to a great extent impaired. This study aimed to analyze data on whole genome expression signatures of undescended testes at risk of developing azoospermia. Twenty-three testicular biopsies from 22 boys were analyzed (19 testes from 18 boys with cryptorchidism) and 4 contralateral descended testes from patients with testicular agenesis. Expression profiling identified 483 genes not or under-expressed in the azoospermia risk group compared with the control and LAZR groups. Annotated loci were associated with spermatogenesis. Other significant genes were cellular defense response genes and hormone controlled loci involved in spermatogenesis. Some genes transcribed in normal adult meiotic and post-meiotic germ cells are activated in healthy juvenile Ad spermatogonia. Thus, molecular events initiating the testicular expression program at the onset of puberty and maintaining it during adulthood occur very early in prepubertal testes. This molecular event is to a great extent impaired in HAZR group lacking Ad spermatogonia (stem cells for spermatozoa) indicating impaired mini puberty.
2010-11-23 | E-GEOD-25518 | biostudies-arrayexpress
Project description:During male development, the testes move from a high intraabdominal position and descend into the scrotum. The gubernaculum, an inguinoscrotal ligament connecting the testis to the lower abdomen, is believed to play a critical role in this process. The first stage of testicular descent is controlled by INSL3, insulin like3 hormone, produced in testicular Leydig cells. Deletion of Insl3 or its receptor, Rxfp2, in mice causes cryptorchidism. We produced Cre/loxP regulated shRNA transgenic mice targeting RXFP2 expression. We have shown that the transgene was able to reduce Rxfp2 gene expression and thus behaved as a hypomorphic allele of Rxfp2. Variable degrees of uni-and bilateral cryptorchidism was detected in males with the activated shRNA transgene on an Rxfp2+/- background. Conditional suppression of Rxfp2 in the gubernaculum led to cryptorchidism. Gene expression analysis of a mutant cremasteric sac using Illumina microarrays indicated abnormal expression of a significant number of genes in Wnt/β-catenin and Notch pathways. We have demonstrated profound changes in the expression pattern of β-catenin, Notch1, desmin, and androgen receptor (AR) in Rxfp2-/- male embryos, indicating the role of INSL3 in proliferation, differentiation, and survival of specific cellular components of the gubernaculum. We have shown that INSL3/RXFP2 signaling is essential for myogenic differentiation and maintenance of AR-positive cells in the gubernaculum. Males with the deletion of β-catenin or Notch1 in the gubernacular ligament demonstrated abnormal development. Our data indicates that β-catenin and Notch pathways are potential targets of INSL3 signaling during gubernacular development. Total RNA obtained from the cremasteric sac of cryptorchid Tg(shRxfp1) males compared to the wild-type control cremasteric sac.
2010-11-10 | E-GEOD-25222 | biostudies-arrayexpress
Project description:The Long Evans/orl (LE/orl) rat is an animal model of inherited undescended testis (UDT). To explore genetic mechanisms of UDT, we studied differential gene expression in LE/orl and LE wild type (LE/wt) fetal gubernaculum and testis. Analyses of differentially expressed probe sets linked below as supplementary files: Analysis_methods.txt [A description of the analysis] gub.txt [Genes differentially expressed in between wt and orl gubernacula] testes.txt [Genes differentially expressed between wt and orl testes] wt.txt [Genes differentially expressed in wt gubernacular development] Keywords: strain/condition predisposition, disease state analysis, developmental
2008-02-03 | GSE7755 | GEO
Project description:During male development, the testes move from a high intraabdominal position and descend into the scrotum. The gubernaculum, an inguinoscrotal ligament connecting the testis to the lower abdomen, is believed to play a critical role in this process. The first stage of testicular descent is controlled by INSL3, insulin like3 hormone, produced in testicular Leydig cells. Deletion of Insl3 or its receptor, Rxfp2, in mice causes cryptorchidism. We produced Cre/loxP regulated shRNA transgenic mice targeting RXFP2 expression. We have shown that the transgene was able to reduce Rxfp2 gene expression and thus behaved as a hypomorphic allele of Rxfp2. Variable degrees of uni-and bilateral cryptorchidism was detected in males with the activated shRNA transgene on an Rxfp2+/- background. Conditional suppression of Rxfp2 in the gubernaculum led to cryptorchidism. Gene expression analysis of a mutant cremasteric sac using Illumina microarrays indicated abnormal expression of a significant number of genes in Wnt/β-catenin and Notch pathways. We have demonstrated profound changes in the expression pattern of β-catenin, Notch1, desmin, and androgen receptor (AR) in Rxfp2-/- male embryos, indicating the role of INSL3 in proliferation, differentiation, and survival of specific cellular components of the gubernaculum. We have shown that INSL3/RXFP2 signaling is essential for myogenic differentiation and maintenance of AR-positive cells in the gubernaculum. Males with the deletion of β-catenin or Notch1 in the gubernacular ligament demonstrated abnormal development. Our data indicates that β-catenin and Notch pathways are potential targets of INSL3 signaling during gubernacular development.
2010-11-10 | GSE25222 | GEO
Project description:Central and peripheral hormone deficiencies have been documented during and after acute hantavirus infection. Thrombocytopenia and coagulation abnormalities are common findings in haemorrhagic fever with renal syndrome (HFRS). The associations between coagulation and hormonal abnormalities in HFRS have not been studied yet. Forty-two patients diagnosed with Puumala virus (PUUV) infection were examined during the acute phase and on a follow-up visit approximately one month later. Hormonal defects were common during acute PUUV infection. Overt (clinical) hypogonadism was identified in 80% of the men and approximately 20% of the patients had overt hypothyroidism. At the one-month follow-up visit, six patients had central hormone deficits. Acute peripheral hormone deficits associated with a more severe acute kidney injury (AKI), longer hospital stay and more severe thrombocytopenia. Half of the patients with bleeding symptoms had also peripheral hormonal deficiencies. Patients with free thyroxine levels below the reference range had higher D-dimer level than patients with normal thyroid function, but no thromboembolic events occurred. Acute phase hormonal abnormalities associate with severe disease and altered haemostasis in PUUV infection.
| S-EPMC8472102 | biostudies-literature
Project description:The Long Evans/orl (LE/orl) rat is an animal model of inherited undescended testis (UDT). To explore genetic mechanisms of UDT, we studied differential gene expression in LE/orl and LE wild type (LE/wt) fetal gubernaculum and testis. Analyses of differentially expressed probe sets linked below as supplementary files:; Analysis_methods.txt [A description of the analysis]; gub.txt [Genes differentially expressed in between wt and orl gubernacula]; testes.txt [Genes differentially expressed between wt and orl testes]; wt.txt [Genes differentially expressed in wt gubernacular development] Experiment Overall Design: Fetuses were harvested from timed matings of LE/wt and LE/orl rats at gestational day (GD) 17, 18, 19, and 20. Single gubernaculum and testis were removed from male fetuses and total RNA was isolated from each organ. Left organs were used, except for GD 20 fetuses where both right and left gubernacula were included. For female fetuses, the right and left gubernacula from a single fetus were pooled before RNA isolation. A total of 54 samples were hybridized to GeneChips; 34 gubernacular samples and 20 testes samples. There were 13 sample groups, each included biological replicate arrays. The sample groups were (1) female LE/wt GD18 gubernacula n=4, (2) male LE/wt GD18 left gubernacula n=4, (3) male LE/wt GD19 left gubernacula n=4, (4) male LE/wt GD20 left gubernacula n=4, (5) male LE/wt GD20 right gubernacula n=3, (6) male LE/orl GD18 left gubernacula n=4, (7) male LE/orl GD19 left gubernacula n=4, (8) male LE/orl GD20 left gubernacula n=4, (9) male LE/orl GD20 right gubernacula n=3, (10) male LE/wt GD17 left testes n=5, (11) male LE/wt GD19 left testes n=5, (12) male LE/orl GD17 left testes n=5, and (13) male LE/orl GD19 left testes n=5.
2008-06-15 | E-GEOD-7755 | biostudies-arrayexpress
Project description:Despite timely and successful surgery, 32% of patients with bilateral and 10% with unilateral cryptorchidism will develop azoospermia. Cryptorchid boys at risk of azoospermia display a typical testicular histology of impaired mini-puberty at the time of the orchidopexy. During mini-puberty increased gonadotropin and testosterone secretion stimulate transformation of gonocytes into Ad spermatogonia. In azoospermia risk group this transformation is to a great extent impaired. This study aimed to analyze data on whole genome expression signatures of undescended testes at risk of developing azoospermia.
2010-11-23 | GSE25518 | GEO