ORIGINAL ARTICLE Silymarin modulates cadmium-induced oxidative stress in human spermatozoa Tahereh Etemadi | Hamid Reza Momeni | Niloufar Darbandi | Mohammad Hussein Abnosi Biology Department, Faculty of Science, Arak University, Arak, Iran Correspondence Hamid Reza Momeni, Biology Department, Faculty of Science, Arak University, Arak, Iran. Email: h-momeni@araku.ac.ir Funding information Arak University Abstract Environmental pollutants such as cadmium can negatively affect sperm parameters and decrease male fertility by inducing oxidative stress. Antioxidants are considered a useful strategy for oxidative stress conditions to neutralize free radicals and strengthen the antioxidant defence system. In this study, the effects of the common application of silymarin, as a natural antioxidant, with cadmium were assessed on human sperm. The washed human sperm samples were divided into five groups: (1) spermatozoa at 0- hour; (2) spermatozoa at 3 h; (3) spermatozoa treated with cad- mium (20 μM) for 3 h; (4) spermatozoa treated with silymarin (2 μM) + cadmium (20 μM) for 3 h and (5) spermatozoa treated with silymarin (2 μM) for 3 h. Our results displayed that cadmium reduced sperm motility, viability, plasma membrane integrity and acrosome integrity by increasing malondialdehyde levels and decreasing the total antioxidant capacity and antioxidant enzymes activity. While silymarin attenuated oxidative stress biomarkers in human sperm treated with cadmium, and consequently improved the sperm quality. In summary, cadmium-induced oxidative stress impaired human sperm structures and silymarin with its antioxidant properties compensated for the adverse effects of oxidative stress on human spermatozoa. KEYWORDS antioxidant enzymes, cadmium chloride, male infertility, milk thistle plant 1 | INTRODUCTION Elevated levels of oxidative stress biomarkers in the semen 30–80% infertile men may suggest pivotal role of oxidative stress in the pathol- ogy of male infertility (Tremellen, 2008). Accordingly, numerous stud- ies have revealed that oxidative stress attenuates male fertility by affecting some sperm structures such as the membranes (Bisht et al., 2017; Saleh & HCLD, 2002). The fact that the plasma mem- brane plays critical roles in vital sperm parameters, such as sperm motility, viability, and acrosome reaction, the integrity of plasma mem- brane is a key factor for sperm physiological process, fertilization abil- ity, and consequently male fertility (Moskovtsev et al., 2005; Ramirez et al., 1992). Besides, the high content of poly-unsaturated fatty acids (PUFAs) in spermatozoa plasma membrane increases its vulnerability to oxidative stress (Wathes et al., 2007). In addition, due to the very little amount of the cytoplasm, spermatozoa suffer from insufficient antioxidant defence system (Agarwal & Prabakaran, 2005). Heavy metals are known to induce oxidative stress (Flora et al., 2008). Cadmium is a heavy metal and major environmental pol- lutant that is widely used in smelting, pigment, battery and plastic pro- duction, as well as in alloys, soldering and plating (Johri et al., 2010). Humans may therefore be exposed to cadmium through contaminated water and food, smoking and inhalation (Bernhoft, 2013). Cadmium is not a redox-active agent, acting differently from other toxic metals such as arsenic, lead, and mercury (Machado-Neves, 2022). This heavy metal with a long biological half-life (15–20 years) accumulates in the blood, kidneys, liver and reproductive organs over time (Goering et al., 1995). It was shown that exposure to cadmium causes poor Received: 24 March 2022 Revised: 28 April 2022 Accepted: 3 May 2022 DOI: 10.1111/and.14475 Andrologia. 2022;54:e14475. wileyonlinelibrary.com/journal/and © 2022 Wiley-VCH GMbH. 1 of 9 https://doi.org/10.1111/and.14475