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Seyededeh Sedigheh Hosseini,1,2 Hamidreza Joshaghani,3 Tahereh Shokohi,4 Alireza Ahmadi,1 Zahra Mehrbakhsh5 1Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran; 2Department of Laboratory Sciences, Faculty of Paramedicine, Gorgan University of Medical Sciences, Gorgan, Iran; 3Department of Clinical Biochemistry, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran; 4Department of Medical Mycology and Parasitology, Mazandaran University of Medical Sciences, Sari, Iran; 5Department of Biostatistics and Epidemiology, School of Health, Golestan University of Medical Sciences, Gorgan, IranCorrespondence: Seyededeh Sedigheh HosseiniLaboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan 4934174515, IranTel +9891137571228Fax +9832423630Email Hosseini.s@goums.ac.irPurpose: Antifungal resistance and virulence properties of Candida albicans (C. albicans) are growing health problems worldwide. The present study aims to investigate the effect of Zinc Oxide (ZnO) nanoparticles and Nystatin on SAP1-3 genes expression in C. albicans isolates of females with Vulvovaginal Candidiasis (VVC) isolated from Sayad Shirazi Obstetrics and Gynecology Hospital in Northeastern Iran during 2017– 2018.Patients and Methods: In this descriptive-analytic study, vaginal samples were collected from 280 VVC women. 196 (70%) of C. albicans isolates were identified by phenotypic and ITS genotypic methods. Susceptibility to Fluconazole C. albicans isolates was determined by the disk diffusion method. Detection of ERG11 gene was done by RT-PCR technique.Results: It was revealed that PCR amplified the ERG11 gene in all of the Fluconazole-resistant isolates. Real-time PCR was used to survey the effects of 3± 1.7μg/mL concentrations of ZnO nanoparticles and Nystatin on expression of SAP1-3 genes before and after treatment. 186 (95%) susceptible C. albicans and 10 (5%) Fluconazole-resistant C. albicans isolates from VVC were exposed to sub-minimum inhibitory concentrations (Sub-MIC) of ZnO-np (range=0.02– 12 μg/mL). Sub-MIC concentration was used for each strain, which reduced the expression of SAP1-3 genes to 1.8 MIC in the vaginal swabs. The observed reduction in gene expression was significant for both ZnO nanoparticles and Nystatin (P=0.01 and P=0.07, respectively).Conclusion: ZnO as antifungal agent can well reduce the growth and gene expression of SAP1-3 in the pathogenesis of VVC.Keywords: ZnO, gene expression, pathogenesis, vulvovaginal candidiasis