World Journal of Advanced Research and Reviews, 2020, 07(02), 075081 World Journal of Advanced Research and Reviews e-ISSN: 2581-9615, Cross Ref DOI: 10.30574/wjarr Journal homepage: https://www.wjarr.com Corresponding author: Ahmed Ibrahim Younus Copyright © 2020 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. (R ESEARCH A RTICLE ) Reproductive toxicity of iron oxide nanoparticles, silver nanoparticles and their mixture in male rats: Effects on testicular gene expression Ahmed Ibrahim Younus 1, * , Mokhtar Ibrahim Yousef 2 , Kamel Maher Abdel-Nabi 3 , Mohammed Ibrahim Younus 4 and Jubran Mohammed Abdulrahman 5 1 Ministry of Health, Iraq. 2 Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Egypt. 3 Department of Biochemistry, Medical Research Institute, Alexandria University, Egypt. 4 College of Medicine, University of Anbar, Ministry of Higher Education and Scientific Research, Iraq. 5 Center of Research and Educational Studies, Ministry of Education, Iraq. Publication history: Received on 25 July 2020; revised on 08 August 2020; accepted on 10 August 2020 Article DOI: https://doi.org/10.30574/wjarr.2020.7.2.0278 Abstract Iron oxide nanoparticles (Fe2O3NPs) have shown wide biological applications in magnetic resonance imaging (MRI), drug delivery, gene therapy, cancer treatments, in vitro diagnostics (IVD), and vaccine and antibody production. Although Fe2O3NPs have a variety of applications, few studies have demonstrated that exposure to Fe2O3NPs may lead to adverse effects, such as reproductive toxicity. Silver nanoparticles (AgNPs) are widely used in products across industries; they are often used for their antimicrobial activity in medicine and are also often found in detergents. Few studies have demonstrated that exposure to AgNPs may lead to adverse effects, such as reproductive toxicity. There is no enough results on the reproductive toxicity induced by Fe2O3NPs and AgNPs, especially in combination. Therefore, the present study aimed to investigate the reproductive toxicity of iron oxide nanoparticles, silver nanoparticles and their combination in male rats. In the present study Wistar male rats were used. Animals were divided into 4 equal groups, 10 rats each. Group 1 served as control, group 2 was administered orally with Fe2O3NPs (5 mg/kg BW; >50 nm), group 3 was treated intraperitoneally with AgNPs (50 mg/kg BW; >100 nm) and group 4 was administered with the mixture of Fe2O3NPs with AgNPs. Animals were treated with doses every day for 79 days. Treatment with Fe2O3NPs, AgNPs and their combination caused significant (P < 0.05) changed in gene expression of mitochondrial transcription factor-A (mtTFA) and uncoupling protein 2 (UCP 2) in testes compared to control group. Keywords: Iron oxide nanoparticles; Silver nanoparticles; Male rats; Gene expression 1. Introduction In recent years, reproductive and developmental toxicity has increasingly become recognized as an important part of overall toxicology. In fact, adverse effects of environmental chemicals on the reproductive success of wildlife populations have been noted [1]. It is reported that nanoparticles can pass through biological Membranes raising fears that they can affect the physiology of any cell in the body. The possibility of chemicals entering biological systems is of great concern to the public with regard to possible reproductive and developmental toxicity [2, 3]. Mitochondria contain their own genome. Mitochondrial DNA (mtDNA) is located in the mitochondrial matrix and is present in multiple copies per mitochondrion (4). It consists of a light strand, a heavy strand (rich in guanine) and a small fragment called the displacement loop or D-loop. mtDNA does not contain introns and both strands of circular mtDNA are transcribed as long primary transcripts corresponding to several genes. These primary transcripts are processed to release the individual tRNA, rRNA and mRNA [5]. The mitochondrial function and biogenesis is under the control of nuclear encoded proteins; mainly mitochondrial transcription factor A (mtTFA) and uncoupling proteins (UCPs) [6, 7]. Mitochondrial transcription factor A (mtTFA) gene is a single copy nuclear gene which encodes for an activator of