scholarly journals E2F1 regulates testicular descent and controls spermatogenesis by influencing WNT4 signaling

Development ◽  
2021 ◽  
Vol 148 (1) ◽  
pp. dev191189
Author(s):  
Carolina J. Jorgez ◽  
Abhishek Seth ◽  
Nathan Wilken ◽  
Juan C. Bournat ◽  
Ching H. Chen ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Copy Number Variations ◽  
Testicular Descent ◽  
Null Mouse ◽  
Testicular Tumors ◽  
Predisposing Factor ◽  
Novel Approach ◽  
Fertility Potential ◽  
Spermatogenic Failure

ABSTRACTCryptorchidism is the most common urologic birth defect in men and is a predisposing factor of male infertility and testicular cancer, yet the etiology remains largely unknown. E2F1 microdeletions and microduplications contribute to cryptorchidism, infertility and testicular tumors. Although E2f1 deletion or overexpression in mice causes spermatogenic failure, the mechanism by which E2f1 influences testicular function is unknown. This investigation revealed that E2f1-null mice develop cryptorchidism with severe gubernacular defects and progressive loss of germ cells resulting in infertility and, in rare cases, testicular tumors. It was hypothesized that germ cell depletion resulted from an increase in WNT4 levels. To test this hypothesis, the phenotype of a double-null mouse model lacking both Wnt4 and E2f1 in germ cells was analyzed. Double-null mice are fertile. This finding indicates that germ cell maintenance is dependent on E2f1 repression of Wnt4, supporting a role for Wnt4 in germ cell survival. In the future, modulation of WNT4 expression in men with cryptorchidism and spermatogenic failure due to E2F1 copy number variations may provide a novel approach to improve their spermatogenesis and perhaps their fertility potential after orchidopexy.

Evaluation of degenerating germ cells in normal juvenile mice

Genome ◽  
2009 ◽  
Vol 52 (10) ◽  
pp. 891-896 ◽  
Author(s):  
Anastassia Trifonova ◽  
Peter B. Moens
Keyword(s):  
Cell Death ◽  
Germ Cell ◽  
Germ Cells ◽  
Normal Component ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Electron Microscopic ◽  
Cell Degeneration ◽  
Novel Approach ◽  
Two Generations ◽  
Germ Cell Degeneration

Absence of spermiogenesis in mice with meiotic defects complicates the staging of meiotic arrest using light microscopy. Consequently, new methodologies are required to establish accurate relationships among germ cells. In this study, we utilized a novel approach to analyze germ cell degeneration in juvenile mice. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in combination with meiosis-specific antibodies. Germ cell degeneration is a normal component of early spermatogenesis in juvenile mice. The incidence of germ cell death was monitored at various postnatal ages of mice using the TUNEL assay to quantify the incidence of apoptosis. Cell death occurred predominantly at 15.5 days after birth. It was found that groups of apoptotic cells were apparent in tubules containing two generations of spermatocytes that form in two progressive cohorts. Electron microscopic observations further illustrated that the majority of cells in the first cohort are in late pachytene, while groups of cells in the second cohort can degenerate in early pachytene. The methodology utilized in this study is significant because it allows one to accurately determine the point at which germ cells arrest. Consequently, we believe that these methods can be applied to study animals with meiotic defects that prevent spermiogenesis.

GATA-like protein-1 (GLP-1) is required for normal germ cell development during embryonic oogenesis

Reproduction ◽  
2011 ◽  
Vol 141 (2) ◽  
pp. 173-181 ◽  
Author(s):  
Tamara J Strauss ◽  
Diego H Castrillon ◽  
Stephen R Hammes
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Germ Line ◽  
Primordial Follicle ◽  
Cell Loss ◽  
Basement Membranes ◽  
Cell Protein ◽  
Null Mouse ◽  
Cell Functions ◽  
Expression Of Genes

Oogenesis and primordial follicle formation are tightly linked processes, requiring organized and precisely timed communication between somatic and germ cells. Deviations in ovarian cell cross talk, or aberrant gene expression within one of the cell populations, can lead to follicle loss or dysfunction, resulting in infertility. Expression of GATA-like protein-1 (GLP-1) in ovarian somatic cells is required for normal fertility in female mice, as GLP-1 deficiency leads to the absence of oocytes at birth. However, the timing and nature of this germ cell loss is not well understood. In this study, we characterize the embryonic germ cell loss in GLP-1 null mice. Quantitative PCR demonstrates that ovarian Glp-1 mRNA is expressed in a bimodal pattern during embryogenesis, peaking at E13.5–14.5 and again at birth. In contrast, adult ovaries express low but detectable levels of Glp-1 mRNA. Analysis of developing GLP-1 null mouse ovaries shows that germ cells are appropriately specified and migrate normally to nascent gonads. Upon arrival at the gonad, precocious loss of germ cells begins at around E13.5. This loss is completed by birth and is accompanied by defects in the expression of genes associated with meiotic entry. Interestingly, somatic pregranulosa cells still form basement membranes surrounding germ line cysts and express mRNA encoding paracrine signaling molecules that communicate with oocytes, albeit at lower levels than normal. Together, these data imply that the somatic cell protein GLP-1 is not necessary for many pregranulosa cell functions but is required for germ cell survival.

scholarly journals Rescue of germ cells in dnd crispant embryos opens the possibility to produce inherited sterility in Atlantic salmon

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hilal Güralp ◽  
Kai O. Skaftnesmo ◽  
Erik Kjærner-Semb ◽  
Anne Hege Straume ◽  
Lene Kleppe ◽  
...  
Keyword(s):  
Atlantic Salmon ◽  
Germ Cell ◽  
Germ Cells ◽  
Large Scale ◽  
Environmental Concern ◽  
Scale Production ◽  
Genetic Introgression ◽  
Cell Stage ◽  
Novel Approach ◽  
Large Scale Production

Abstract Genetic introgression of escaped farmed Atlantic salmon (Salmo salar) into wild populations is a major environmental concern for the salmon aquaculture industry. Using sterile fish in commercial aquaculture operations is, therefore, a sustainable strategy for bio-containment. So far, the only commercially used methodology for producing sterile fish is triploidization. However, triploid fish are less robust. A novel approach in which to achieve sterility is to produce germ cell-free salmon, which can be accomplished by knocking out the dead-end (dnd) gene using CRISPR-Cas9. The lack of germ cells in the resulting dnd crispants, thus, prevents reproduction and inhibits subsequent large-scale production of sterile fish. Here, we report a rescue approach for producing germ cells in Atlantic salmon dnd crispants. To achieve this, we co-injected the wild-type (wt) variant of salmon dnd mRNA together with CRISPR-Cas9 constructs targeting dnd into 1-cell stage embryos. We found that rescued one-year-old fish contained germ cells, type A spermatogonia in males and previtellogenic primary oocytes in females. The method presented here opens a possibility for large-scale production of germ-cell free Atlantic salmon offspring through the genetically sterile broodstock which can pass the sterility trait on the next generation.

Electron microscope study of the effects of radiation on insect fertility

1990 ◽  
Vol 48 (3) ◽  
pp. 72-73
Author(s):  
Judy Ju-Hu Chiang ◽  
Robert Kuo-Cheng Chen
Keyword(s):  
Electron Microscopy ◽  
Germ Cell ◽  
Germ Cells ◽  
Electron Microscope Study ◽  
Radiation Treatment ◽  
Light And Electron Microscopy ◽  
Stem Borer ◽  
Metabolic Energy ◽  
Rice Stem Borer ◽  
Effects Of Radiation

Germ cells from the rice stem borer Chilo suppresalis, were examined by light and electron microscopy. Damages to organelles within the germ cells were observed. The mitochondria, which provide the cell with metabolic energy, were seen to disintegrate within the germ cell. Lysosomes within the germ cell were also seen to disintegrate. The subsequent release of hydrolytic enzymesmay be responsible for the destruction of organelles within the germ cell. Insect spermatozoa were seen to lose the ability to move because of radiation treatment. Damage to the centrioles, one of which is in contact with the tail, may be involved in causing sperm immobility.

Examination of the dynamics of global DNA methylation pattern establishment during spermatogenesiss

2007 ◽  
Vol 30 (4) ◽  
pp. 90
Author(s):  
Kirsten Niles ◽  
Sophie La Salle ◽  
Christopher Oakes ◽  
Jacquetta Trasler
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cells ◽  
Epigenetic Modification ◽  
Methylation Pattern ◽  
Chromosome 9 ◽  
Specific Gene ◽  
Global Methylation ◽  
Dna Methylation Pattern ◽  
Methylation Patterns

Background: DNA methylation is an epigenetic modification involved in gene expression, genome stability, and genomic imprinting. In the male, methylation patterns are initially erased in primordial germ cells (PGCs) as they enter the gonadal ridge; methylation patterns are then acquired on CpG dinucleotides during gametogenesis. Correct pattern establishment is essential for normal spermatogenesis. To date, the characterization and timing of methylation pattern acquisition in PGCs has been described using a limited number of specific gene loci. This study aimed to describe DNA methylation pattern establishment dynamics during male gametogenesis through global methylation profiling techniques in a mouse model. Methods: Using a chromosome based approach, primers were designed for 24 regions spanning chromosome 9; intergenic, non-repeat, non-CpG island sequences were chosen for study based on previous evidence that these types of sequences are targets for testis-specific methylation events. The percent methylation was determined in each region by quantitative analysis of DNA methylation using real-time PCR (qAMP). The germ cell-specific pattern was determined by comparing methylation between spermatozoa and liver. To examine methylation in developing germ cells, spermatogonia from 2 day- and 6 day-old Oct4-GFP (green fluorescent protein) mice were isolated using fluorescence activated cell sorting. Results: As compared to liver, four loci were hypomethylated and five loci were hypermethylated in spermatozoa, supporting previous results indicating a unique methylation pattern in male germ cells. Only one region was hypomethylated and no regions were hypermethylated in day 6 spermatogonia as compared to mature spermatozoa, signifying that the bulk of DNA methylation is established prior to type A spermatogonia. The methylation in day 2 spermatogonia, germ cells that are just commencing mitosis, revealed differences of 15-20% compared to day 6 spermatogonia at five regions indicating that the most crucial phase of DNA methylation acquisition occurs prenatally. Conclusion: Together, these studies provide further evidence that germ cell methylation patterns differ from those in somatic tissues and suggest that much of methylation at intergenic sites is acquired during prenatal germ cell development. (Supported by CIHR)

Sonographic Diagnosis of Unilateral Synchronous Testicular Tumors

2019 ◽  
Vol 2 ◽  
pp. 2
Author(s):  
Allison Forrest ◽  
Numbereye Numbere ◽  
Jerome Jean-Gilles ◽  
Thomas Frye ◽  
Vikram Dogra
Keyword(s):  
Testicular Cancer ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Histological Type ◽  
Synchronous Tumors ◽  
Testicular Tumors ◽  
Sonographic Diagnosis ◽  
Histological Types ◽  
Common Cancer

Testicular cancer accounts for 1% of all male cancers yet is the most common cancer affecting men aged 15–44 years. Most testicular cancers are seminomas or non-seminomatous germ cell tumors. Rarely, multiple testicular cancers may occur simultaneously, most often of the same histological type. However, synchronous tumors of different histological types may occur, although rarely. In this case study, we present the sonographic features with histopathologic correlation in a case of unilateral synchronous testicular tumors of discordant histology.

scholarly journals Characterization of Estrogenic Activity and Site-Specific Accumulation of Bisphenol-A in Epididymal Fat Pad: Interfering Effects on the Endocannabinoid System and Temporal Progression of Germ Cells

2021 ◽  
Vol 22 (5) ◽  
pp. 2540
Author(s):  
Teresa Chioccarelli ◽  
Marina Migliaccio ◽  
Antonio Suglia ◽  
Francesco Manfrevola ◽  
Veronica Porreca ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Germ Cell ◽  
Germ Cells ◽  
Estrogenic Activity ◽  
Endocannabinoid System ◽  
Perinatal Period ◽  
Cell Junction ◽  
Cell Content ◽  
Site Specific ◽  
Epididymal Fat

The objective of this work has been to characterize the estrogenic activity of bisphenol-A (BPA) and the adverse effects on the endocannabinoid system (ECS) in modulating germ cell progression. Male offspring exposed to BPA during the foetal-perinatal period at doses below the no-observed-adverse-effect-level were used to investigate the exposure effects in adulthood. Results showed that BPA accumulates specifically in epididymal fat rather than in abdominal fat and targets testicular expression of 3β-hydroxysteroid dehydrogenase and cytochrome P450 aromatase, thus promoting sustained increase of estrogens and a decrease of testosterone. The exposure to BPA affects the expression levels of some ECS components, namely type-1 (CB1) and type-2 cannabinoid (CB2) receptor and monoacylglycerol-lipase (MAGL). Furthermore, it affects the temporal progression of germ cells reported to be responsive to ECS and promotes epithelial germ cell exfoliation. In particular, it increases the germ cell content (i.e., spermatogonia while reducing spermatocytes and spermatids), accelerates progression of spermatocytes and spermatids, promotes epithelial detachment of round and condensed spermatids and interferes with expression of cell–cell junction genes (i.e., zonula occcludens protein-1, vimentin and β-catenin). Altogether, our study provides evidence that early exposure to BPA produces in adulthood sustained and site-specific BPA accumulation in epididymal fat, becoming a risk factor for the reproductive endocrine pathways associated to ECS.

scholarly journals Predictors of Venous Thromboembolism in Patients With Testicular Germ Cell Tumors: A Retrospective Study

2021 ◽  
Vol 27 ◽  
pp. 107602962110247
Author(s):  
Hikmat Abdel-Razeq ◽  
Faris Tamimi ◽  
Rashid Abdel-Razeq ◽  
Samer Salah ◽  
Zaid Omari ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Germ Cell ◽  
Metastatic Disease ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Tumor Burden ◽  
Testicular Tumors ◽  
Testicular Germ Cell ◽  
Node Positive ◽  
Age Range

Malignancy, including testicular tumors, significantly increases the risk of venous thromboembolism (VTE). In this study, we search for predictors that may help identify subgroups of patients at higher risk of VTE. Patients with confirmed diagnosis of testicular germ cell tumor and proven VTE were identified. Clinical and pathological features possibly associated with VTE were reviewed. A total of 322 patients, median age (range) 31 (18-76) years were identified. Tumors were mostly non-seminoma (n = 194, 60.2%), node-positive (n = 130, 40.4%) and 58 (18.0%) had metastatic disease at diagnosis. Venous thromboembolism were confirmed in 27 (8.4%) patients; however, rates were significantly higher ( P < 0.001) in patients with node-positive (18.5%), metastatic disease (22.4%), and those with high lactate dehydrogenase (LDH) (21.3%). Rates were also significantly higher among those who received multiple lines of chemotherapy (27.5%) compared to those who received one line (13.8%) or none (<1.0%), P < 0.001. Patients with testicular tumors and high tumor burden, including nodal involvement, high LDH or metastatic disease, and those treated with multiple lines of chemotherapy have significantly higher rates of VTE.

Analysis of the CAG tract length in the Androgen Receptor gene in Mexican patients with nonsyndromic cryptorchidism

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Daniel A. Landero-Huerta ◽  
Rosa M. Vigueras-Villaseñor ◽  
Lucía Taja-Chayeb ◽  
Fabiola García-Andrade ◽  
Elena Aréchaga-Ocampo ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Germ Cell ◽  
Receptor Gene ◽  
Germ Cell Tumors ◽  
Androgen Receptor Gene ◽  
Testicular Descent ◽  
Healthy Individuals ◽  
Testicular Germ Cell ◽  
Molecular Alteration ◽  
Mexican Patients

Abstract Objectives Cryptorchidism is the most common genitourinary birth defect in live newborn males and is considered as an important risk factor for testicular germ cell tumors and infertility. The Androgen Receptor gene is important in this pathology due to its participation, mainly, in the inguinoscrotal phase of testicular descent. We determine the length of the CAG tract in the Androgen Receptor (AR) gene in Mexican patients with nonsyndromic cryptorchidism. Methods One hundred and 15 males were included; of these, 62 had nonsyndromic cryptorchidism and 53 were healthy volunteers. DNA was extracted from a peripheral blood samples, subsequently, the CAG tract in exon 1 of AR gene was amplified by PCR and sequenced. Results Mexican patients with nonsyndromic cryptorchidism presented 25.03 ± 2.58 repeats of CAG tract in the AR gene compared to 22.72 ± 3.17 repeats of CAG tract in Mexican healthy individuals (p≤0.0001; t value of 4.3). Furthermore, the deletion of codon 57 that corresponds to the deletion of a leucine residue at position 57 (Del L57) in the AR gene was found for the first time in a nonsyndromic cryptorchidism patient. This molecular alteration has been related previously to testicular germ cell tumor (TGCT). Conclusions The CAG tract in the AR gene is longer in patients with nonsyndromic cryptorchidism than in healthy individuals, supporting the association between this polymorphism of the AR gene and nonsyndromic cryptorchidism in the Mexican population.

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