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Quantification of KRAS inhibitor sotorasib in mouse plasma and tissue homogenates using liquid chromatography-tandem mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Apr 20;1174:122718. Epub 2021 Apr 20.

Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacology, Universiteitsweg 99, 3584 CG Utrecht, the Netherlands. Electronic address:

Sotorasib is a KRAS inhibitor with promising anticancer activity in phase I clinical studies. This compound is currently under further clinical evaluation as monotherapy and combination therapy against solid tumors. In this study, a liquid chromatography-tandem mass spectrometric method to quantify sotorasib in mouse plasma and eight tissue-related matrices (brain, liver, spleen, kidney, small intestine, small intestine content, lung, and testis homogenates) was developed and validated. Read More

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Exploring the Ion Channel TRPV2 and Testicular Macrophages in Mouse Testis.

Int J Mol Sci 2021 Apr 29;22(9). Epub 2021 Apr 29.

Cell Biology-Anatomy III, Biomedical Center Munich (BMC), Faculty of Medicine, Ludwig-Maximilian-University (LMU), D-82152 Planegg-Martinsried, Germany.

The cation channel TRPV2 is known to be expressed by murine macrophages and is crucially involved in their functionality. Macrophages are frequent cells of the mouse testis, an immune-privileged and steroid-producing organ. TRPV2 expression by testicular macrophages and possible changes associated with age or inflammation have not been investigated yet. Read More

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Alternative splicing during mammalian organ development.

Nat Genet 2021 May 3. Epub 2021 May 3.

Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Heidelberg, Germany.

Alternative splicing (AS) is pervasive in mammalian genomes, yet cross-species comparisons have been largely restricted to adult tissues and the functionality of most AS events remains unclear. We assessed AS patterns across pre- and postnatal development of seven organs in six mammals and a bird. Our analyses revealed that developmentally dynamic AS events, which are especially prevalent in the brain, are substantially more conserved than nondynamic ones. Read More

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Expression and Prognostic Significance of Cancer/Testis Antigens, MAGE-E1, GAGE, and SOX-6, in Glioblastoma: An Immunohistochemistry Evaluation.

Iran J Pathol 2021 20;16(2):128-136. Epub 2020 Dec 20.

Department of Medical Genetics, Mashhad University of Medical Sciences, Mashhad, Iran.

Background & Objective: Glioblastoma is the most common primary malignancy of the brain, the prognosis of which is poor. Immunotherapy with cancer/testis (CT) antigens is a novel therapeutic approach for glioblastoma. This study aimed to investigate the expression rate of MAGE-E1, GAGE, and SOX-6 in glioblastoma tumors using the method of immunohistochemistry (IHC). Read More

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December 2020

A transgenic reporter mouse model for assessment of retinoic acid receptor transcriptional activation.

Int J Vitam Nutr Res 2021 Apr 30:1-13. Epub 2021 Apr 30.

Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

Vitamin A is essential for a wide range of life processes throughout embryogenesis to adult life. With the aim of developing an model to monitor retinoic acid receptor (RAR) transactivation real-time in intact animals, we generated transgenic mice carrying a luciferase (luc) reporter gene under the control of retinoic acid response elements (RAREs) consisting of three copies of a direct repeat with five spacing nucleotides (DR5). : Transgenic mice carrying a RARE dependent luciferase reporter flanked with insulator sequence were generated by pronuclear injection. Read More

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Tissue Antioxidant Status and Lipid Peroxidation Are Related to Dietary Intake of n-3 Polyunsaturated Acids: A Rabbit Model.

Antioxidants (Basel) 2021 Apr 27;10(5). Epub 2021 Apr 27.

Department of Agricultural, Environmental and Food Science, University of Perugia, Borgo 20 Giugno, 74, 06123 Perugia, Italy.

Polyunsaturated fatty acid (PUFA) metabolism and tissue distribution is modulated by the oxidation of these molecules. This research aimed to investigate the implication of dietary n-3 PUFA supplementation (precursor and long-chain PUFA) on the PUFA profile and oxidative status of the liver, testis, and brain of adult rabbit bucks. Twenty New Zealand White rabbit bucks were divided into four experimental groups ( = 5 per group) and were fed different diets for 110 days: control (CNT), standard diet containing 50 mg/kg alpha-tocopheryl acetate (vitamin E); CNT+, standard diet + 200 mg/kg vitamin E; FLAX, standard diet + 10% flaxseed + 200 mg/kg vitamin E; or FISH, standard diet + 3. Read More

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Genomic Structure of the Porcine Locus and Expression of the Paralog.

Genes (Basel) 2021 Apr 6;12(4). Epub 2021 Apr 6.

Department of Animal Science, College of Agricultural and Environmental Sciences, University of California, Davis, CA 95616, USA.

Proper, tissue-specific regulation of , the gene encoding aromatase, the key enzyme of estrogen synthesis, is essential for reproductive processes. Here, we analyzed transcriptional regulation of the porcine in female and male gonads and brain by 5'RACE and RT-PCR and comprehensively mapped the pig locus by in silico analysis. Our data revealed that the complete locus, including three paralogous copies, , and , spans approximately 330 kb of the porcine chromosome 1. Read More

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Metallobiochemistry of ultratrace levels of bismuth in the rat II. Interaction of Bi with tissue, intracellular and molecular components.

J Trace Elem Med Biol 2021 Apr 20:126752. Epub 2021 Apr 20.

Department of Physics, Università Degli Studi di Milano, Via Celoria 16, Milano, I-20133, Italy; LASA, Department of Physics, Università Degli Studi di Milano and INFN-Milano, Via F.lli Cervi 201, Segrate, MI, I-20090, Italy. Electronic address:

Background: Knowledge on Bi metabolism in laboratory animals refers to studies at "extreme" exposures, i.e. pharmacologically relevant high-doses (mg kg b. Read More

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Detection of truncated isoforms of human neuroserpin lacking the reactive center loop: Implications in noninhibitory role.

IUBMB Life 2021 Apr 23. Epub 2021 Apr 23.

Department of Biosciences, Jamia Millia Islamia, New Delhi, India.

Neuroserpin is a serine protease inhibitor expressed mainly in the brain and at low levels in other tissues like the kidney, testis, heart, and spinal cord. It is involved in the inhibition of tissue plasminogen activator (tPA), plasmin, and to a lesser extent, urokinase-type plasminogen (uPA). Neuroserpin has also been shown to plays noninhibitory roles in the regulation of N-cadherin-mediated cell adhesion. Read More

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Effects of cadmium and high-fat diet on essential metal concentration in the mouse testis.

Toxicol Rep 2021 20;8:718-723. Epub 2021 Mar 20.

Department of Pharmacology and Toxicology, University of LouisvilleSchool of Medicine, University of Louisville, USA.

The effects of exposure to the environmental toxicant cadmium, in combination with obesity, on the metal content in mouse testis were evaluated. Starting in utero and continuing through to 10 or 24 weeks post-weaning, male mice were exposed to cadmium (0, 0.5 or 5 ppm), and fed either a low (LFD) or high fat diet (HFD) post-weaning. Read More

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The cocaine and oxycodone biobanks, two repositories from genetically diverse and behaviorally characterized rats for the study of addiction.

eNeuro 2021 Apr 15. Epub 2021 Apr 15.

Department of Psychiatry, University of California, San Diego, La Jolla CA 92093, USA

Substance use disorders are pervasive in our society and have substantial personal and socio-economical costs. A critical hurdle in identifying biomarkers and novel targets for medication development is the lack of resources for obtaining biological samples with a detailed behavioral characterization of substance use disorder. Moreover, it is nearly impossible to find longitudinal samples. Read More

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An In Vitro Assay to Monitor Sertoli Cell Blood-Testis Barrier (BTB) Integrity.

Methods Mol Biol 2021 Apr 9. Epub 2021 Apr 9.

The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.

In this chapter, we detail a reliable, effective, and easy to perform assay to monitor the Sertoli cell blood-testis barrier (BTB) integrity. While the BTB in the testis is composed of the tight junction (TJ) barrier and basal ES (ectoplasmic specialization, a testis-specific actin-rich adherens junction (AJ) type), this method is applicable to all other blood-tissue barrier in vitro, including endothelial TJ-barrier of the blood-brain barrier (BBB). Furthermore, this method does not require expensive set up, and can be rapidly performed by any standard biochemistry/cell biology/molecular biology laboratory. Read More

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Systemic dengue infection associated with a new dengue virus type 2 introduction in Brazil - a case report.

BMC Infect Dis 2021 Apr 1;21(1):311. Epub 2021 Apr 1.

Laboratory of Molecular Evolution and Bioinformatics, Department of Microbiology, Biomedical Sciences Institute, University of São Paulo, São Paulo, Brazil.

Background: Dengue infection is caused by an arbovirus with a wide range of presentations, varying from asymptomatic disease to unspecific febrile illness and haemorrhagic syndrome with shock, which can evolve to death. In Brazil, the virus circulates since the 1980s with many introductions of new serotypes, genotypes, and lineages since then. Here we report a fatal case of dengue associated with a Dengue virus (DENV) lineage not detected in the country until now. Read More

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ABCB1 and ABCG2 Restrict Brain and Testis Accumulation and, Alongside CYP3A, Limit Oral Availability of the Novel TRK Inhibitor Selitrectinib.

Mol Cancer Ther 2021 Mar 30. Epub 2021 Mar 30.

Division of Pharmacology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.

Selitrectinib (BAY2731954; LOXO-195) is a promising oral tropomyosin receptor kinase (TRK) inhibitor currently in phase I/II clinical trials for the treatment of histology-agnostic cancers positive for TRK fusions. With therapeutic resistance eventually developing with first-generation TRK inhibitors, selitrectinib was designed to overcome resistance mediated by acquired kinase domain mutations. Using genetically modified mouse models and pharmacological inhibitors, we investigated the roles of the multidrug efflux transporters ABCB1 and ABCG2, and the drug-metabolizing CYP3A enzyme complex in selitrectinib pharmacokinetics. Read More

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Molecular identification of an androgen receptor and the influence of long-term aggressive interaction on hypothalamic genes expression in black rockfish (Sebastes schlegelii).

J Comp Physiol A Neuroethol Sens Neural Behav Physiol 2021 May 27;207(3):401-413. Epub 2021 Mar 27.

Fisheries College, Zhejiang Ocean University, Zhoushan, 316022, China.

This study aims to explore the mechanism on how aggressive interaction alters reproductive physiology by testing whether aggressive interaction can activate the reproductive neuroendocrine function via the hypothalamus-pituitary-gonadal (HPG) axis in black rockfish (Sebastes schlegelii). The expressions of the androgen receptor gene (ar) and gonadotropin-releasing hormone genes (gnrhs), the concentration of plasma androgens, and GSI (the ratio of testes mass to body mass) were compared between the interaction group (dominant males or subordinate males) and the isolation group in male black rockfish after 3 weeks. A full-length cDNA encoding an androgen receptor (AR) of 766 amino acids was isolated. Read More

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Tight junctions and their regulation by non-coding RNAs.

Int J Biol Sci 2021 31;17(3):712-727. Epub 2021 Jan 31.

Department of Dermatology, Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, Hunan 410013, P.R. China.

Tight junction (TJ) is a "zippering up" junction structure located at the uppermost portion of adjacent epithelial/endothelial cells in organs and tissues. TJs maintain the relative stability of intracellular substances and functions by closing or opening intercellular pathways, coordinating the entry and exit of molecules of different sizes and charges, and regulating the permeability of paracellular barrier. TJs also prevent microbial invasion, maintain epithelial/endothelial cell polarity, and regulate cell proliferation. Read More

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January 2021

cDNA cloning, expression and bioinformatical analysis of Tssk genes in tree shrews.

Comput Biol Chem 2021 Mar 10;92:107474. Epub 2021 Mar 10.

Faculty of Animal Science and Technology, Yunnan Agricultural University, Kunming, 650201, China. Electronic address:

Tree shrews are more closely related to primate animals than rodents in many aspects. In addition, they also possess several advantageous characteristics including small body size, high brain-to-body mass ratio, low cost of feeding and maintenance, short reproductive cycle and life span, which make them promising novel laboratory animals to replace more precious larger primate animals. Testis-specific serine/threonine kinase (Tssk) plays important roles in spermatogenesis and/or the regulation of sperm function. Read More

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CTCFL expression is associated with cerebral vascular abnormalities.

Tissue Cell 2021 Mar 16;72:101528. Epub 2021 Mar 16.

Departments of Genetics and Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.

CTCFL is expressed in testis, oocytes and embryonic stem cells, and is aberrantly expressed in malignant cells, and is classified as a cancer-testis gene. We have previously shown by using a tetracycline-inducible Ctcfl transgene that inappropriate expression of Ctcfl negatively impacts fetal development and causes early postnatal lethality in the mouse. The affected pups displayed severe vascular abnormalities and localized hemorrhages in the brain evocative of cerebral cavernous malformations (CCM) and arteriovenous malformations (AVM) in humans. Read More

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Deposition and metabolism of dietary -3 very-long-chain PUFA in different organs of rat, mouse and Atlantic salmon.

Br J Nutr 2021 Mar 10:1-20. Epub 2021 Mar 10.

Nofima (Norwegian Institute of Food, Fisheries and Aquaculture Research), 1432 Ås, Norway.

There is limited knowledge about the metabolism and function of n-3 very-long-chain PUFA (n-3 VLC-PUFA) with chain lengths ≥ 24. They are known to be produced endogenously in certain tissues from EPA and DHA and not considered to originate directly from dietary sources. The aim of this study was to investigate whether n-3 VLC-PUFA from dietary sources are bio-available and deposited in tissues of rat, fish and mouse. Read More

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Molecular clues in the regulation of mini-puberty involve neuronal DNA binding transcription factor NHLH2.

Basic Clin Androl 2021 Mar 18;31(1). Epub 2021 Mar 18.

Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.

Gonadotropin releasing hormone agonist (GnRHa) treatment following surgery to correct cryptorchidism restores mini-puberty via endocrinological and transcriptional effects and prevents adult infertility in most cases. Several genes are important for central hypogonadotropic hypogonadism in mammals, including many that are transcribed in both the brain and testis. However, the expression of these genes in prepubertal gonads has not been studied systematically, and little is known about the effect of hormone therapy on their testicular and neuronal expression levels. Read More

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Identification and sequence analysis of prolactin receptor and its differential expression profile at various developmental stages in striped hamsters.

Braz J Med Biol Res 2021 15;54(5):e10274. Epub 2021 Mar 15.

College of Life Sciences, Qufu Normal University, Qufu, Shandong, China.

Prolactin (PRL) plays critical roles in regulation of biological functions with the binding of specific prolactin receptor (PRLR). Revealing the expression patterns of PRLR at different developmental stages is beneficial to better understand the role of PRL and its mechanism of action in striped hamsters. In this study, the cDNA sequence of PRLR (2866-base-pairs) was harvested from the pituitary of mature female striped hamsters (Cricetulus barabensis) that contains an 834-base-pair 5'-untranslated region (1-834 bp), a 1848-base-pair open reading frame (835-2682 bp), and a 184-base-pair 3'-untranslated region (2683-2866). Read More

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Expression of tyrosine pathway enzymes in mice demonstrates that homogentisate 1,2-dioxygenase deficiency in the liver is responsible for homogentisic acid-derived ochronotic pigmentation.

JIMD Rep 2021 Mar 12;58(1):52-60. Epub 2020 Nov 12.

Department of Musculoskeletal & Ageing Science, Institute of Life Course and Medical Science University of Liverpool Liverpool United Kingdom.

Alkaptonuria (AKU) is caused by homogentisate 1,2-dioxygenase (HGD) deficiency. This study aimed to determine if HGD and other enzymes related to tyrosine metabolism are associated with the location of ochronotic pigment. Liver, kidney, skin, bone, brain, eyes, spleen, intestine, lung, heart, cartilage, and muscle were harvested from 6 AKU BALB/c (3 females, 3 males) and 4 male C57BL/6 wild type (WT) mice. Read More

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The Role of Cold Inducible RNA-Binding Protein in Cardiac Physiology and Diseases.

Front Pharmacol 2021 24;12:610792. Epub 2021 Feb 24.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Cold-inducible RNA-binding protein (CIRP) is an intracellular stress-response protein that can respond to various stress conditions by changing its expression and regulating mRNA stability. As an RNA-binding protein, CIRP modulates gene expression at the post-transcriptional level, including those genes involved in DNA repair, cellular redox metabolism, circadian rhythms, telomere maintenance, and cell survival. CIRP is expressed in a large variety of tissues, including testis, brain, lung, kidney, liver, stomach, bone marrow, and heart. Read More

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February 2021

Structures of the germline-specific Deadhead and thioredoxin T proteins from reveal unique features among thioredoxins.

IUCrJ 2021 Mar 11;8(Pt 2):281-294. Epub 2021 Feb 11.

Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028 Barcelona, Spain.

Thioredoxins (Trxs) are ubiquitous enzymes that regulate the redox state in cells. In , there are two germline-specific Trxs, Deadhead (Dhd) and thioredoxin T (TrxT), that belong to the lethal(3)malignant brain tumor signature genes and to the 'survival network' of genes that mediate the cellular response to DNA damage. Dhd is a maternal protein required for early embryogenesis that promotes protamine-histone exchange in fertilized eggs and midblastula transition. Read More

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Investigating the acute and sub-acute toxicity of medicinal Cuscuta chinensis Lam plant.

J Ethnopharmacol 2021 Jun 8;273:114005. Epub 2021 Mar 8.

School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China. Electronic address:

Ethnopharmacology Relevance: Cuscuta chinensis Lam. (Convolvulaceae) had received growing attention as a traditional medicinal herb widely used for treating female impotence, abortion, male reproductive system disease and cardiovascular diseases, respectively.

Aim Of The Study: The present study investigated the acute and sub-acute toxicities of C. Read More

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Gonadal lipidomics profile of an ovoviviparity teleost, black rockfish, during gonadal development.

Fish Physiol Biochem 2021 Mar 10. Epub 2021 Mar 10.

Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, People's Republic of China.

In order to study the variation of gonad lipidomics during reproductive cycle, black rockfish was employed as the research model in the present study. Using histology, lipidomics, and qPCR, the profile of gonad lipidomics and the expression levels of related genes during different developmental stages were detected and analyzed to show the potential regulatory network of lipid metabolism. Based on Ultra High-Performance Liquid Tandem Chromatography Quadrupole Time of Flight Mass Spectrometry (UHPLC-QTOFMS), four significant differential glycerophospholipid metabolic pathways including phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidic acid (PA) were enriched by KEGG. Read More

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Toxicity assessment of watermelon seed supplemented diet in rats.

Drug Chem Toxicol 2021 Mar 7:1-8. Epub 2021 Mar 7.

Department of Anatomy, Bowen University, Iwo, Nigeria.

Health benefits have been attributed to the consumption of watermelon ( L.) seeds in sub-Saharan Africa and Asia but the potential toxicity especially on chronic use remains to be investigated. Here, diets containing watermelon seeds (WMSs) at 2. Read More

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Exploring the Stress Impact in the Paternal Germ Cells Epigenome: Can Catecholamines Induce Epigenetic Reprogramming?

Front Endocrinol (Lausanne) 2020 19;11:630948. Epub 2021 Feb 19.

Instituto de Investigaciones Farmacológicas (Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.

Spermatogenesis is characterized by unique epigenetic programs that enable chromatin remodeling and transcriptional regulation for proper meiotic divisions and germ cells maturation. Paternal lifestyle stressors such as diet, drug abuse, or psychological trauma can directly impact the germ cell epigenome and transmit phenotypes to the next generation, pointing to the importance of epigenetic regulation during spermatogenesis. It is established that environmental perturbations can affect the development and behavior of the offspring through epigenetic inheritance, including changes in small non-coding RNAs, DNA methylation, and histones post-translational modifications. Read More

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February 2021

Chronic exposure of bisphenol S (BPS) affect hypothalamic-pituitary-testicular activities in adult male rats: possible in estrogenic mode of action.

Environ Health Prev Med 2021 Mar 7;26(1):31. Epub 2021 Mar 7.

Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.

Background: The industrial revolution has resulted in increased synthesis and the introduction of a variety of compounds into the environment and their potentially hazardous effects have been observed in the biota. The present study was aimed to evaluate the potential endocrine-disrupting effects of chronic exposure to the low concentrations of bisphenol S (BPS) in male rats.

Methods: Weaning male Sprague-Dawley rats (22 days old) were either exposed to water containing 0. Read More

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Zika virus disrupts the barrier structure and Absorption/Secretion functions of the epididymis in mice.

PLoS Negl Trop Dis 2021 Mar 5;15(3):e0009211. Epub 2021 Mar 5.

Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

Several studies have demonstrated that Zika virus (ZIKV) damages testis and leads to infertility in mice; however, the infection in the epididymis, another important organ of male reproductive health, has gained less attention. Previously, we detected lesions in the epididymis in interferon type I and II receptor knockout male mice during ZIKV infection. Herein, the pathogenesis of ZIKV in the epididymis was further assessed in the infected mice after footpad inoculation. Read More

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