A major public health issue that affects millions of people worldwide is infertility [1]. It is estimated that approximately 40–50 % of this condition is caused by the male gender [2]. Furthermore, DNA fragmentation is linked to infertility and impacts implantation, rates of in vitro and in vivo fertilization, pregnancy, embryonic development, and sperm [3]. However, one of the most important features of apoptosis is DNA fragmentation [4]. During spermatogenesis, apoptosis is a crucial regulator of germ cell growth [5]. Additionally, DNA fragmentation occurs in sperm during apoptosis caused by oxidative stress [6]. In male gender, age, lifestyle, genetic, and pathological variables, environmental toxins and some types of cancer may cause DNA fragmentation in sperm [7], [8]. Infertility is one of the many diseases that can be brought on by environmental toxins. Cadmium (Cd) is a toxic heavy metal. Particularly in terms of reproductive toxicity, Cd presents a serious risk to the public's health [9]. Many studies have disclosed that male reproductive organs are hypersensitive to Cd due to metabolism and active cell division. The sperm must overcome several obstacles during activation to reach fertilization competence before fusion with the oocyte [10]. Ion channels on the sperm membrane are typically what trigger these physiological processes leading to fertilization. Sperm-specific calcium and potassium channels (CatSper - KSper) are important in regulating the physiological functions of sperm and thus, male fertility. However, Cd concentrations that cause male infertility impair the functional activity of these channels, resulting in decreased sperm viability and motility [11]. According to epidemiological studies, Cd and male infertility are positively associated [8]. For example, in a meta-analysis of 11 studies (1093 infertile and 614 controls), it was declared that a high Cd level in semen caused male infertility [12].

Monoterpenes are a subgroup of terpenes and are isoprene derivatives that are responsible for the aromatic character of plants [13]. Linalool (Lnl) is a monoterpene that is a component of various essential oils derived from many plants, such as lavender, cardamom, etc. Additionally, Lnl can also be produced synthetically [14]. These compounds may cross the blood-brain barrier due to their low molecular weight and high lipophilicity. Therefore, they can be used in the pharmaceutical treatment of behavioral and cognitive changes [15]. On the other hand, it has been documented that Lnl increases the anti-inflammatory capacity by inhibiting inflammatory signals generated by Nuclear factor kappa B (NF-κB). Furthermore, Lnl lowers nitric oxide, reactive oxygen species (ROS), and cytokine production [13], [16]. Research showed that Lnl has a therapeutic and protective effect against doxorubicin-induced cardiotoxicity, an antineoplastic agent [17]. According to a different study, Lnl can suppress liver inflammation in response to CCl4-induced hepatotoxicity by lowering pro-inflammatory cytokines and controlling anti-inflammatory cytokines [18]. However, Lnl showed anti-inflammatory and anti-oxidant effects in a streptozotocin-induced experimental diabetic nephropathy model [19]. In addition to these effects, Lnl also has anti-cancer, sedative, anxiolytic, and anticonvulsant effects [20], [21].

To the best of our knowledge, no prior research has been done on the therapeutic potential of Lnl against testicular tissue damage caused by Cd. Thus, the purpose of this investigation was to ascertain whether Lnl protects against testicular toxicity caused by Cd. Additionally, the aim is to determine how Otulin, a new deubiquitinase known to play a role in the regulation of the NF-κB pathway and Tumor necrosis factor (TNF-α) signaling [22], is affected by Lnl application against Cd-induced testicular toxicity.