Review
Medicine, Research & Experimental
Waseem Ali, Kai Deng, Yusheng Bian, Zongping Liu, Hui Zou
Summary: The epididymis is responsible for sperm maturation by creating a favorable environment for spermatozoa. Recent evidence suggests that exosomes, which contain important bio-active cargo elements, facilitate communication between the epididymis and spermatozoa. Proteomic analysis of exosomes from the epididymis indicates their role in sperm motility, acrosomal reaction, and male infertility. This review highlights the distinctive characteristics and functions of nano-scale exosomes in the male reproductive tract, emphasizing their importance in male reproduction, fertility, and disease susceptibility.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemical Research Methods
Natalie A. Trigg, Simone J. Stanger, Wei Zhou, David A. Skerrett-Byrne, Petra Sipila, Matthew D. Dun, Andrew L. Eamens, Geoffry N. De Iuliis, Elizabeth G. Bromfield, Shaun D. Roman, Brett Nixon
Summary: The study identified the critical role of the MFGE8 protein in mediating efficient exchange of macromolecular cargo between sperm and extracellular vesicles, with the RGD domain of MFGE8 being particularly important. Through various strategies, significant inhibition of protein uptake and redistribution into immature sperm was observed, implicating the MFGE8 ligand and its integrin receptor in the interactions that support sperm maturation.
Article
Biochemistry & Molecular Biology
Guangxin Yao, Shengsong Xie, Xiaofeng Wan, Ling Zhang, Qiang Liu, Shuanggang Hu
Summary: The study identifies and characterizes rLcn13, a member of the rat epididymal lipocalin family. rLcn13 is found to be an epididymis-specific gene expressed predominantly in the initial segment and proximal caput epididymis, and influenced by androgen. The protein rLCN13 is modified by N-glycosylation, secreted into the epididymal lumen, and binds to the acrosome region of the sperm. The findings highlight the specific expression pattern and potential roles of rLcn13 in sperm maturation.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2023)
Article
Agriculture, Dairy & Animal Science
Ziqiang Ding, Lin Xiong, Xingdong Wang, Shaoke Guo, Mengli Cao, Yandong Kang, Yongfu La, Pengjia Bao, Jie Pei, Xian Guo
Summary: In this study, key genes regulating the development of the epididymal cauda and sperm maturation in yak were identified using RNA-seq and proteomics. These findings provide a theoretical basis for improving the reproductive potential of yak.
Article
Agriculture, Dairy & Animal Science
Katarzyna Dyrda, Aleksandra Orzolek, Joanna Ner-Kluza, Pawel Wysocki
Summary: Phosphorylation and dephosphorylation of proteins play crucial roles in sperm maturation during epididymal transit. Differences in phosphorylation status were observed in certain proteins, potentially impacting sperm maturation and fertilization capability.
Article
Andrology
Yoo-Jin Park, Byeong-Mu Lee, Won-Ki Pang, Do-Yeal Ryu, Md Saidur Rahman, Myung-Geol Pang
Summary: This study investigated the relationship between sequential changes in protein expression during epididymal sperm maturation and sperm motility and fertility in bovine. The study found that irregular modifications of mitochondrial proteins during epididymal sperm maturation may lead to excessive ROS production and premature activation of spermatozoa, resulting in a decline in sperm motility and bull fertility.
WORLD JOURNAL OF MENS HEALTH
(2022)
Article
Veterinary Sciences
Wangsheng Zhao, Siraj Ahmed, Junxia Liu, Saeed Ahmed, Eugene Quansah, Tajmal Hussain Solangi, Yitao Wu, Yueling Yangliu, Hongmei Wang, Jiangjiang Zhu, Xin Cai
Summary: This study utilized iTRAQ proteomics to analyze differentially abundant proteins in yak and cattleyak epididymis, revealing 151 up-regulated and 137 down-regulated proteins in cattleyak compared to yak. Gene Ontology analysis showed that down-regulated proteins in cattleyak were primarily enriched in protein component acetylation, as well as negative and positive regulatory activities.
BMC VETERINARY RESEARCH
(2021)
Article
Agriculture, Dairy & Animal Science
Cuiling Wu, Chunxin Wang, Bo Zhai, Yunhui Zhao, Zhuo Zhao, Zhiyu Yuan, Mingxin Zhang, Kechuan Tian, Xuefeng Fu
Summary: The study analyzed the miRNA expression profiles in different regions of ram epididymis, revealing important roles of multiple miRNAs in regulating sperm maturation in males. This provides valuable insights for studying the regulation mechanism of sperm maturation and improving reproductive performance.
REPRODUCTION IN DOMESTIC ANIMALS
(2021)
Article
Genetics & Heredity
Junjie Hu, Wenbo Ge, Longfei Xiao, Jianlin Zeng, Jianshu Lv, Ziqiang Ding, Wenjuan Wang, Hongwei Duan, Fadi Li
Summary: The study investigated the regulatory mechanism of progesterone on the secretion of dihydrotestosterone in sheep epididymis, revealing different synthesis abilities of P4 in different parts of the epididymis and higher PGR expression levels in the cauda. In vitro cell culture experiments showed that inhibition of DHT secretion and 5 alpha-reductase 1 and 2 expression by P4 could be partially mitigated by RU486.
Article
Biochemistry & Molecular Biology
Alessia Gloria, Alberto Contri, Elena Mele, Silvia Fasano, Riccardo Pierantoni, Rosaria Meccariello
Summary: The study found the presence of the Kisspeptin system in dog testis and spermatozoa, indicating a significant role of the system in sperm maturation and storage. The trafficking of Kiss1R towards the plasma membrane along the length of the epididymis and the presence of Kiss1 in epididymal fluid suggest a new functional role of the Kisspeptin system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Felipe Couto-Santos, Arabela Guedes de Azevedo Viana, Ana Claudia Ferreira Souza, Alexandre Augusto de Assis Dutra, Tiago Antonio de Oliveira Mendes, Andre Teixeira da Silva Ferreira, Jonas Enrique Perales Aguilar, Leandro Licursi Oliveira, Mariana Machado-Neves
Summary: Arsenic exposure during prepubertal stage reduces sperm production, epididymal sperm count, motility, and quality in sexually mature rats, leading to low fertility potential and high preimplantation loss. Proteomic and phosphoproteomic analysis revealed alterations in protein expression and phosphorylation patterns, indicating potential pathways involved in the deleterious effects of arsenic on male fertility.
Article
Biochemical Research Methods
Jess E. Mulhall, Natalie A. Trigg, Ilana R. Bernstein, Amanda L. Anderson, Heather C. Murray, Petra Sipila, Tessa Lord, John E. Schjenken, Brett Nixon, David A. Skerrett-Byrne
Summary: The testes and vas deferens are separated by the epididymis, a tubule with a unique microenvironment that is crucial for sperm maturation. The epididymal epithelium creates this microenvironment through the release of extracellular vesicles and small non-coding RNAs. In this study, the authors used mass spectrometry to compare the protein profiles of an immortalized mouse epididymal epithelial cell line to native mouse epididymal epithelial cells. They found that many proteins identified in the cell line were also present in native cells, supporting the use of this cell line as an in vitro model for studying epididymal epithelial cell function.
Article
Obstetrics & Gynecology
F. Barrachina, M. A. Battistone, J. Castillo, C. Mallofre, M. Jodar, S. Breton, R. Oliva
Summary: The study demonstrates that sperm acquire proteins from epididymosomes during post-testicular maturation, providing insights into the mechanisms of sperm maturation and potential therapeutic strategies for male infertility. The results highlight the novel role of epididymal clear cells in producing epididymosomes, contributing to a better understanding of male reproductive health.
HUMAN REPRODUCTION
(2022)
Review
Andrology
Nilendu Paul, Thirumala Rao Talluri, Pradeep Nag, Arumugam Kumaresan
Summary: Epididymosomes play a crucial role in the maturation and fertilizing ability of sperm by transferring proteins, RNA, and lipids from the epididymis to sperm cells. Research on epididymosomes has gained increasing attention in recent years and has the potential to be utilized as a tool for male fertility assessment.
Article
Developmental Biology
Brett Nixon, Amanda L. Anderson, Elizabeth G. Bromfield, Jacinta H. Martin, Shenae L. Cafe, David A. Skerrett-Byrne, Matthew D. Dun, Andrew L. Eamens, Geoffry N. De Iuliis, Stephen D. Johnston
Summary: Research focused on the physiology of saltwater crocodile sperm, showing an increasing gradient of sperm motility as they transit the male reproductive tract, and that increasing intracellular cAMP levels significantly enhance sperm motility. This study paves the way for developing artificial reproductive technologies and opportunistic recovery, storage, and potential utilization of post-mortem spermatozoa from genetically valuable animals.
REPRODUCTION FERTILITY AND DEVELOPMENT
(2021)
Article
Oncology
Dana Messinger, Micah K. Harris, Jessica R. Cummings, Chase Thomas, Tao Yang, Stefan R. Sweha, Rinette Woo, Robert Siddaway, Martin Burkert, Stefanie Stallard, Tingting Qin, Brendan Mullan, Ruby Siada, Ramya Ravindran, Michael Niculcea, Abigail Dowling, Joshua Bradin, Kevin F. Ginn, Melissa A. H. Gener, Kathleen Dorris, Nicholas A. Vitanza, Susanne Schmidt, Jasper Spitzer, Li Jiang, Mariella G. Filbin, Xuhong Cao, Maria G. Castro, Pedro R. Lowenstein, Rajen Mody, Arul Chinnaiyan, Pierre-Yves Desprez, Sean McAllister, Matthew D. Dun, Cynthia Hawkins, Sebastian M. Waszak, Sriram Venneti, Carl Koschmann, Viveka Nand Yadav
Summary: This study found that upregulation of the protein ID1 is associated with H3K27M and ACVR1 mutations in diffuse midline gliomas (DMG). Experimental evidence shows that ID1 plays a role in tumor growth and invasion, and inhibition of ID1 with cannabidiol (CBD) can decrease invasion and growth of DMG tumors. This discovery may provide new possibilities for the treatment of DMG.
Article
Oncology
Nicholas A. Vitanza, Ashley L. Wilson, Wenjun Huang, Kristy Seidel, Christopher Brown, Joshua A. Gustafson, Jason K. Yokoyama, Adam J. Johnson, Blake A. Baxter, Ryan W. Koning, Aquene N. Reid, Michael Meechan, Matthew C. Biery, Carrie Myers, Stephanie D. Rawlings-Rhea, Catherine M. Albert, Samuel R. Browd, Jason S. Hauptman, Amy Lee, Jeffrey G. Ojemann, Michael E. Berens, Matthew D. Dun, Jessica B. Foster, Erin E. Crotty, Sarah E. S. Leary, Bonnie L. Cole, Francisco A. Perez, Jason N. Wright, Rimas J. Orentas, Tony Chour, Evan W. Newell, Jeffrey R. Whiteaker, Lei Zhao, Amanda G. Paulovich, Navin Pinto, Juliane Gust, Rebecca A. Gardner, Michael C. Jensen, Julie R. Park
Summary: This study reports the first administration of repeatedly dosed intracranial B7-H3 CAR T cells for patients with DIPG, indicating tolerability, detection of CAR T cells in the CSF, elevation of CSF cytokines supporting locoregional immune activation, and the feasibility of serial mass spectrometry from both serum and CSF.
Article
Biochemical Research Methods
Heather C. Murray, Kasey Miller, Joshua S. Brzozowski, Richard G. S. Kahl, Nathan D. Smith, Sean J. Humphrey, Matthew D. Dun, Nicole M. Verrills
Summary: Acute myeloid leukemia (AML) is a highly aggressive form of leukemia with a poor prognosis. Mutations in kinases, such as FLT3 and KIT, are common in AML patients and are associated with treatment resistance. This study identified DNA-PK as a potential therapeutic target in AML and demonstrated that DNA-PK inhibition sensitizes AML cells with FLT3 and KIT mutations to standard treatments. The findings suggest that targeting DNA-PK could improve the outcomes of AML patients with these mutations.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Oncology
Claire Xin Sun, Paul Daniel, Gabrielle Bradshaw, Hui Shi, Melissa Loi, Nicole Chew, Sarah Parackal, Vanessa Tsui, Yuqing Liang, Mateusz Koptyra, Shazia Adjumain, Christie Sun, Wai Chin Chong, Dasun Fernando, Caroline Drinkwater, Motahhareh Tourchi, Dilru Habarakada, Dhanya Sooraj, Diana Carvalho, Phillip B. Storm, Valerie Baubet, Leanne C. Sayles, Elisabet Fernandez, Thy Nguyen, Mia Poerksen, Anh Doan, Duncan E. Crombie, Monty Panday, Nataliya Zhukova, Matthew D. Dun, Louise E. Ludlow, Bryan Day, Brett W. Stringer, Naama Neeman, Jeffrey A. Rubens, Eric H. Raabe, Maria Vinci, Vanessa Tyrrell, Jamie I. Fletcher, Paul G. Ekert, Biljana Dumevska, David S. Ziegler, Maria Tsoli, Nur Farhana Syed Sulaiman, Amos Hong Pheng Loh, Sharon Yin Yee Low, E. Alejandro Sweet-Cordero, Michelle Monje, Adam Resnick, Chris Jones, Peter Downie, Bryan Williams, Joseph Rosenbluh, Daniel Gough, Jason E. Cain, Ron Firestein
Summary: The study establishes a pediatric cancer model resource with 261 cell lines, including 224 representing childhood tumor types. Through multi-omics analysis and genetic screening, specific treatment opportunities and biomarkers in pediatric tumor classes are identified. The findings are of great significance in improving the clinical relevance of pediatric cancer treatment.
Article
Oncology
Evangeline R. Jackson, Ryan J. Duchatel, Dilana E. Staudt, Mika L. Persson, Abdul Mannan, Sridevi Yadavilli, Sarah Parackal, Shaye Game, Wai Chin Chong, W. Samantha N. Jayasekara, Marion Le Grand, Padraic S. Kearney, Alicia M. Douglas, Izac J. Findlay, Zacary P. Germon, Holly P. McEwen, Tyrone S. Beitaki, Adjanie Patabendige, David A. Skerrett-Byrne, Brett Nixon, Nathan D. Smith, Bryan Day, Neevika Manoharan, Sumanth Nagabushan, Jordan R. Hansford, Dinisha Govender, Geoff B. McCowage, Ron Firestein, Meegan Howlett, Raelene Endersby, Nicholas G. Gottardo, Frank Alvaro, Sebastian M. Waszak, Martin R. Larsen, Yolanda Colino-Sanguino, Fatima Valdes-Mora, Andria Rakotomalala, Samuel Meignan, Eddy Pasquier, Nicolas Andre, Esther Hulleman, David D. Eisenstat, Nicholas A. Vitanza, Javad Nazarian, Carl Koschmann, Sabine Mueller, Jason E. Cain, Matthew D. Dun
Summary: Diffuse midline gliomas are highly lethal childhood cancers. Palliative radiotherapy is the only established treatment with limited survival benefits. ONC201, a combination of a DRD2 antagonist and ClpP agonist, has shown promising preclinical and emerging clinical efficacy in treating diffuse intrinsic pontine gliomas. Further research is needed to understand the mechanisms of response, the impact of recurring genomic features, and the potential combination therapy with a brain penetrant PI3K/Akt inhibitor, paxalisib.
Editorial Material
Oncology
Nicolas Andre, Guy Buyens, Eric Bouffet, David Walker, Matthew D. Dun
Article
Developmental Biology
Siena Barton, Wei Zhou, Leilani L. Santos, Ellen Menkhorst, Guannan Yang, Wan Tinn Teh, Catarina Ang, Tarana Lucky, Evdokia Dimitriadis
Summary: miR-23b-3p expression is increased in the fertile endometrium during receptivity. This study investigates its role in endometrial adhesion and its downstream targets.
Article
Biochemistry & Molecular Biology
Zacary P. Germon, Jonathan R. Sillar, Abdul Mannan, Ryan J. Duchatel, Dilana Staudt, Heather C. Murray, Izac J. Findlay, Evangeline R. Jackson, Holly P. McEwen, Alicia M. Douglas, Tabitha McLachlan, John E. Schjenken, David A. Skerrett-Byrne, Honggang Huang, Marcella N. Melo-Braga, Maximilian W. Plank, Frank Alvaro, Janis Chamberlain, Geoff De Iuliis, R. John Aitken, Brett Nixon, Andrew H. Wei, Anoop K. Enjeti, Yizhou Huang, Richard B. Lock, Martin R. Larsen, Heather Lee, Vijesh Vaghjiani, Jason E. Cain, Charles E. de Bock, Nicole M. Verrills, Matthew D. Dun
Summary: Mutations in FLT3 gene are common in AML patients and associated with poor prognosis. This study found that oxidative stress affects growth and proliferation signaling pathways in FLT3 mutant AML. Inhibition of NOX2, an ROS-producing complex, increased apoptosis of FLT3-mutant AML cells. In mouse models, NOX2 inhibition reduced circulating cancer cells and combined treatment with NOX2 and FLT3 inhibitors improved survival.
Correction
Biochemical Research Methods
Dilana E. Staudt, Heather C. Murray, David A. Skerrett-Byrne, Nathan D. Smith, M. Fairuz B. Jamaluddin, Richard G. S. Kahl, Ryan J. Duchatel, Zacary P. Germon, Tabitha McLachlan, Evangeline R. Jackson, Izac J. Findlay, Padraic S. Kearney, Abdul Mannan, Holly P. McEwen, Alicia M. Douglas, Brett Nixon, Nicole M. Verrills, Matthew D. Dun
CLINICAL PROTEOMICS
(2023)
Review
Endocrinology & Metabolism
Brett Nixon, John E. Schjenken, Nathan D. Burke, David A. Skerrett-Byrne, Hanah M. Hart, Geoffry N. De Iuliis, Jacinta H. Martin, Tessa Lord, Elizabeth G. Bromfield
Summary: Male infertility is a common issue, which affects about 50% of couples seeking assisted reproductive technologies. Traditional diagnostic methods have limitations, and there is a growing focus on assessing sperm quality to accurately predict male fertility. Recent advances in sperm biology and function have provided innovative approaches for diagnosing and treating male infertility.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Editorial Material
Health Care Sciences & Services
Santosh Valvi, Matthew D. Dun, Jordan R. Hansford
LANCET REGIONAL HEALTH-WESTERN PACIFIC
(2023)
Article
Biochemistry & Molecular Biology
Juha Saarikettu, Saara Lehmusvaara, Marko Pesu, Ilkka Junttila, Juha Partanen, Petra Sipila, Matti Poutanen, Jie Yang, Teemu Haikarainen, Olli Silvennoinen
Summary: Snd1 is an RNA-binding protein that plays important roles in gene expression. Deletion of Snd1 in mice leads to decreased fertility, organ and body size, and reduced number of myeloid cells with decreased expression of granule protein genes. Moreover, the deletion of Snd1 affects a relatively small number of gene expressions in the spleen and liver, and reveals its function in hypoxia adaptation through negatively regulating hypoxia-related miRNAs and hypoxia-induced transcription.
Review
Oncology
Sam Humphries, Danielle R. Bond, Zacary P. Germon, Simon Keely, Anoop K. Enjeti, Matthew D. Dun, Heather J. Lee
Summary: Hypoxia plays a role in influencing AML progression through interactions with DNA methylation, limiting the efficacy of hypomethylating agents within the hypoxic bone marrow. Co-treatments that promote cycling of AML cells within the bone marrow or encourage their dissociation from the bone marrow may be necessary for optimal outcomes in AML patients.
CLINICAL EPIGENETICS
(2023)
Review
Oncology
Bryce C. Thomas, Dilana E. Staudt, Alicia M. Douglas, Michelle Monje, Nicholas A. Vitanza, Matthew D. Dun
Summary: Diffuse midline glioma (DMG) is a fatal pediatric cancer that is difficult to treat due to its location and infiltrative nature. Current treatment options have limited effectiveness, and the tumor immune microenvironment (TIME) further reduces the response to therapy. However, chimeric antigen receptor (CAR) T cell therapy shows promise in improving outcomes for DMG patients, and strategies to overcome treatment obstacles are being explored.