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Abstract
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Recent studies have shown that several members of the G-protein-coupled receptors (GPCR) superfamily play
crucial roles in the maintenance of ion–water homeostasis of the sperm and Sertoli cells, development of the
germ cells, formation of the blood barrier, and maturation of sperm. The GPCR, guanyl-nucleotide exchange
factor, membrane traffic protein, and small GTPase genes were analyzed by microarray and bioinformatics
(3513 sperm and Sertoli cell genes). In the microarray analyses of three human cases with different nonobstructive
azoospermia sperm, the expression of GOLGA8IP, OR2AT4, PHKA1, A2M, OR56A1, SEMA3G,
LRRC17, APP, ARHGAP33, RABGEF1, NPY2R, GHRHR, LTB4R2, GRIK5, OR6K6, NAPG, OR6C65, VPS35,
FPR3, and ARL4A was upregulated, while expression of MARS, SIRPG, OGFR, GPR150, LRRK1, and NGEF
was downregulated. There was an increase in GBP3, GBP3, TNF, TGFB3, and CLTC expression in the Sertoli
cells of three human cases with NOA, whereas expression of PAQR4, RRAGD, RAC2, SERPINB8, IRPB1,
MRGPRF, RASA2, SIRPG, RGS2, RAP2A, RAB2B, ARL17, SERINC4, XIAP, DENND4C, ANKRA2, CSTA,
STX18, and SNAP23 were downregulated. A combined analysis of Enrich Shiny Gene Ontology (GO),
STRING, and Cytoscape was used to predict proteins’ molecular interactions and then to recognize master
pathways. Functional enrichment analysis showed that the biological process (BP), regulation of protein
metabolic process, regulation of small GTPase-mediated signal transduction were significantly expressed in
up-/downregulated differentially expressed genes (DEGs) in sperm. In molecular function (MF) experiments of
DEGs that were up-/downregulated, it was found that GPCR activity, guanyl ribonucleotide binding, GTPase
activity and nucleoside-triphosphatase activity were overexpressed. An analysis of GO enrichment findings of
Sertoli cells showed BP and MF to be common DEGs. When these gene mutations have been validated, they
can be used to create new GPCR antagonists or agonists that are receptor-
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