AUTHOR=Xie Shi-Ming , Lai Jia-Xuan , Liu Chu-Qiao , Zhang Xi-Xing , Lin Yong-Miao , Lan Qi-Wen , Hong De-Yao , Chen Xiao-Chuan , Qiao Jing-Da , Mao Yu-Ling 

TITLE=UBR4 deficiency causes male sterility and testis abnormal in Drosophila

JOURNAL=Frontiers in Endocrinology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1165825

DOI=10.3389/fendo.2023.1165825

ISSN=1664-2392

ABSTRACT=<sec><title>Introduction</title><p>It has been established that <italic>UBR4</italic> encodes E3 ubiquitin ligase, which determines the specificity of substrate binding during protein ubiquitination and has been associated with various functions of the nervous system but not the reproductive system. Herein, we explored the role of <italic>UBR4</italic> on fertility with a <italic>Drosophila model</italic>.</p></sec><sec><title>Methods</title><p>Different <italic>Ubr4</italic> knockdown flies were established using the UAS/GAL4 activating sequence system. Fertility, hatchability, and testis morphology were studied, and bioinformatics analyses were conducted. Our results indicated that <italic>UBR4</italic> deficiency could induce male sterility and influent egg hatchability in <italic>Drosophila</italic>.</p></sec><sec><title>Results</title><p>We found that <italic>Ubr4</italic> deficiency affected the testis during morphological analysis. Proteomics analysis indicated 188 upregulated proteins and 175 downregulated proteins in the testis of <italic>Ubr4</italic> knockdown flies. Gene Ontology analysis revealed significant upregulation of <italic>CG11598</italic> and <italic>Sfp65A</italic>, and downregulation of <italic>Pelota</italic> in <italic>Ubr4</italic> knockdown flies. These proteins were involved in the biometabolic or reproductive process in <italic>Drosophila</italic>. These regulated proteins are important in testis generation and sperm storage promotion. Bioinformatics analysis verified that <italic>UBR4</italic> was low expressed in cryptorchidism patients, which further supported the important role of <italic>UBR4</italic> in male fertility.</p></sec><sec><title>Discussion</title><p>Overall, our findings suggest that <italic>UBR4</italic> deficiency could promote male infertility and may be involved in the protein modification of <italic>UBR4</italic> by upregulating <italic>Sfp65A</italic> and <italic>CG11598</italic>, whereas downregulating Pelota protein expression.</p></sec>