Browsing by Subject "Testis"

Now showing 1 - 9 of 9
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    Analysis of Uncharacterized mKiaa1211 Expression during Mouse Development and Cardiovascular Morphogenesis
    (MDPI, 2019-06-22) Snider, Paige L.; Snider, Elizabeth; Simmons, Olga; Conway, Simon J.; Pediatrics, IU School of Medicine
    Mammalian Kiaa1211 and Kiaa1211-like are a homologous pair of uncharacterized, highly conserved genes cloned from fetal and adult brain cDNA libraries. Herein we map the in utero spatiotemporal expression of mKiaa1211 and mKiaa1211L mRNA and their expression patterns in postnatal testis, skin, gastrointestinal, and adipose progenitor tissues. Significantly, mKiaa1211 is present throughout the early stages of mouse heart development, particularly in the second heart field (SHF) lineage as it differentiates from mesenchymal cells into cardiomyocytes. We also show that mKiaa1211 is expressed within several early neuronal tissues destined to give rise to central, peripheral, and sympathetic nervous system structures. Expression profiling revealed that the paralog mKiaa1211L is not expressed during the normal developmental process and that mKiaa1211 expression was noticeably absent from most adult terminally differentiated tissues. Finally, we confirm that a previously uncharacterized CRISPR/CAS-generated mKiaa1211 mouse mutant allele is hypomorphic.
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    CHAPTER 12 - Non-neoplastic diseases of the testis
    (Elsevier, 2020-06-22) Nistal, Manuel; Paniagua, Ricardo; Bostwick, David G.; Cheng, Liang; Pathology and Laboratory Medicine, School of Medicine
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    Emerging Prognostic Biomarkers in Testicular Germ Cell Tumors: Looking Beyond Established Practice
    (Frontiers, 2018-11-28) Chovanec, Michal; Albany, Constantine; Mego, Michal; Montironi, Rodolfo; Cimadamore, Alessia; Cheng, Liang; Pathology and Laboratory Medicine, School of Medicine
    Testicular germ cell tumors are unique among solid cancers. Historically, this disease was deadly if progressed beyond the stage I. The implementation of cisplatin-based chemotherapy regimens has drastically changed the clinical outcome of metastatic testicular cancer. Several biomarkers were established to refine the prognosis by International Germ Cell Collaborative Group in 1997. Among these, the most significant were primary tumor site; metastatic sites, such as non-pulmonary visceral metastases; and the amplitude of serum tumor markers α-fetoprotein, β-chorionic gonadotropin, and lactate dehydrogenase. Since then, oncology has experienced discoveries of various molecular biomarkers to further refine the prognosis and treatment of malignancies. However, the ability to predict the prognosis and treatment response in germ cell tumors did not improve for many years. Clinical trials with novel targeting agents that were conducted in refractory germ cell tumor patients have proven to have negative outcomes. With the recent advances and developments, novel biomarkers emerge in the field of germ cell tumor oncology. This review article aims to summarize the current knowledge in the research of novel prognostic biomarkers in testicular germ cell tumors.
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    Handling and reporting of orchidectomy specimens with testicular cancer: areas of consensus and variation among 25 experts and 225 European pathologists
    (Wiley, 2015-09) Berney, Daniel M.; Algaba, Ferran; Amin, Mahul; Delahunt, Brett; Compérat, Eva; Epstein, Jonathan I.; Humphrey, Peter; Idrees, Mohammed; Lopez-Beltran, Antonio; Magi-Galluzzi, Cristina; Mikuz, Gregor; Montironi, Rodolfo; Oliva, Esther; Srigley, John; Reuter, Victor E.; Trpkov, Kiril; Ulbright, Thomas M.; Varma, Murali; Verrill, Clare; Young, Robert H.; Zhou, Ming; Egevad, Lars; Department of Pathology and Laboratory Medicine, IU School of Medicine
    The handling and reporting of testicular tumours is difficult due to their rarity. METHODS AND RESULTS: A survey developed by the European Network of Uro-Pathology (ENUP) and sent to its members and experts to assess the evaluation of testicular germ cell tumours. Twenty-five experts and 225 ENUP members replied. Areas of disagreement included immaturity in teratomas, reported by 32% of experts but 68% of ENUP. Although the presence of rete testis invasion was reported widely, the distinction between pagetoid and stromal invasion was made by 96% of experts but only 63% of ENUP. Immunohistochemistry was used in more than 50% of cases by 68% of ENUP and 12% of experts. Staging revealed the greatest areas of disagreement. Invasion of the tunica vaginalis without vascular invasion was interpreted as T1 by 52% of experts and 67% of ENUP, but T2 by the remainder. Tumour invading the hilar adipose tissue adjacent to the epididymis without vascular invasion was interpreted as T1: 40% of experts, 43% of ENUP; T2: 36% of experts, 30% of ENUP; and T3: 24% of experts, 27% of ENUP. CONCLUSIONS: There is remarkable consensus in many areas of testicular pathology. Significant areas of disagreement included staging and reporting of histological types, both of which have the potential to impact on therapy
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    Oncological Follow-up Strategies for Testicular Germ Cell Tumours: A Narrative Review
    (Elsevier, 2022-09-07) Kaufmann, Ernest; Antonelli, Luca; Albers, Peter; Cary, Clint; Gillessen Sommer, Silke; Heidenreich, Axel; Oing, Christoph; Oldenburg, Jan; Pierorazio, Phillip Martin; Stephenson, Andrew J.; Fankhauser, Christian Daniel; Urology, School of Medicine
    Context: The aim of this review is to describe the proportion of testicular germ cell tumours (tGCTs) with recurrence, and the timing and anatomical sites of relapse across different disease stages and after different treatment options. We summarise published follow-up protocols and discuss current and future developments to personalise follow-up for patients with tGCT. Evidence acquisition: A systematic literature search was conducted and current guidelines and selected institutional follow-up protocols were reviewed. Evidence synthesis: Of 302 publications, we screened 68 full texts and included 29 studies; 22 of these were retrospective and seven were prospective in nature, contributing data for 20 570 patients. The number of patients included per study ranged from 119 to 2483. We compared the guideline follow-up protocols of the European Society for Medical Oncology, European Association of Urology, National Comprehensive Cancer Network, and American Urological Association, as well as institutional follow-up protocols. The protocols differed in terms of the number, time points, and type of follow-up investigations. Conclusions: Future research should assess how tGCT can be followed to ensure high adherence, define the role of miR-371a-3p microRNA during follow-up, and develop follow-up protocols after curative treatment in the metastatic setting. Patient summary: In this review of follow-up protocols for men with testis cancer, we observed different recommendations and discuss future research areas to improve follow-up for these patients.
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    Phosphatase of regenerating liver 2 (PRL2) deficiency impairs Kit signaling and spermatogenesis
    (ASBMB, 2014-02-07) Dong, Yuanshu; Zhang, Lujuan; Bai, Yunpeng; Zhou, Hong-Ming; Campbell, Amanda M.; Chen, Hanying; Yong, Weidong; Zhang, Wenjun; Zeng, Qi; Shou, Weinian; Zhang, Zhong-Yin; Department of Biochemistry & Molecular Biology, IU School of Medicine
    The Phosphatase of Regenerating Liver (PRL) proteins promote cell signaling and are oncogenic when overexpressed. However, our understanding of PRL function came primarily from studies with cultured cell lines aberrantly or ectopically expressing PRLs. To define the physiological roles of the PRLs, we generated PRL2 knock-out mice to study the effects of PRL deletion in a genetically controlled, organismal model. PRL2-deficient male mice exhibit testicular hypotrophy and impaired spermatogenesis, leading to decreased reproductive capacity. Mechanistically, PRL2 deficiency results in elevated PTEN level in the testis, which attenuates the Kit-PI3K-Akt pathway, resulting in increased germ cell apoptosis. Conversely, increased PRL2 expression in GC-1 cells reduces PTEN level and promotes Akt activation. Our analyses of PRL2-deficient animals suggest that PRL2 is required for spermatogenesis during testis development. The study also reveals that PRL2 promotes Kit-mediated PI3K/Akt signaling by reducing the level of PTEN that normally antagonizes the pathway. Given the strong cancer susceptibility to subtle variations in PTEN level, the ability of PRL2 to repress PTEN expression qualifies it as an oncogene and a novel target for developing anti-cancer agents.
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    Resumption of Puberty in Girls and Boys Following Removal of the Histrelin Implant
    (Elsevier, 2014) Fisher, Marisa M.; Lemay, Deborah; Eugster, Erica A.; Pediatrics, School of Medicine
    Objectives: To determine time to menarche in girls and testicular volume increase in boys after removal of a histrelin implant, which causes profound hypothalamic-pituitary-gonadal axis suppression. Study design: Medical records of patients treated with a histrelin implant were reviewed. Seventy-one patients (56 girls) treated with the histrelin implant were identified, of these patients, 37 explanted girls (68% naïve) and 6 explanted boys (83% naïve) were included in the analysis. Time to menarche after explantation in girls and time to testicular volume increase after explantation in boys were determined. Additional variables investigated included indication for and duration of treatment, history of menarche (girls), previous therapy, and age at beginning and end of histrelin treatment. Results: Of the girls, 30 were treated for central precocious puberty (CPP), 26 had menarche at an average of 12.75 months after explantation. Of the 30, 7 were treated for other indications, of whom 6 had reached menarche. In girls with CPP, older age at explantation correlated with sooner menarche (P = .04). All boys achieved spontaneous testicular enlargement within 1 year of explantation. Conclusions: This study documented resumption of puberty after histrelin explantation in treatment naïve and non-naïve boys and girls with and without CPP. Menarche in girls with CPP occurs within a similar timeframe to that observed after other treatment approaches.
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    The Loss of Tafazzin Transacetylase Activity Is Sufficient to Drive Testicular Infertility
    (MDPI, 2024-11-26) Snider, Paige L.; Sierra Potchanant, Elizabeth A.; Matias, Catalina; Edwards, Donna M.; Brault, Jeffrey J.; Conway, Simon J.; Pediatrics, School of Medicine
    Barth syndrome (BTHS) is a rare, infantile-onset, X-linked mitochondriopathy exhibiting a variable presentation of failure to thrive, growth insufficiency, skeletal myopathy, neutropenia, and heart anomalies due to mitochondrial dysfunction secondary to inherited TAFAZZIN transacetylase mutations. Although not reported in BTHS patients, male infertility is observed in several Tafazzin (Taz) mouse alleles and in a Drosophila mutant. Herein, we examined the male infertility phenotype in a BTHS-patient-derived D75H point-mutant knockin mouse (TazPM) allele that expresses a mutant protein lacking transacetylase activity. Neonatal and adult TazPM testes were hypoplastic, and their epididymis lacked sperm. Histology and biomarker analysis revealed TazPM spermatogenesis is arrested prior to sexual maturation due to an inability to undergo meiosis and the generation of haploid spermatids. Moreover, TazPM testicular mitochondria were found to be structurally abnormal, and there was an elevation of p53-dependent apoptosis within TazPM seminiferous tubules. Immunoblot analysis revealed that TazPM gamete genome integrity was compromised, and both histone γ-H2Ax and Nucleoside diphosphate kinase-5 protein expression were absent in juvenile TazPM testes when compared to controls. We demonstrate that Taz-mediated transacetylase activity is required within mitochondria for normal spermatogenesis, and its absence results in meiotic arrest. We hypothesize that elevated TazPM spermatogonial apoptosis causes azoospermia and complete infertility.