Citalopram Induces Reproductive Toxicity in Male Rats Sinem Ilgin * 1 , Gozde Kilic 2 , Merve Baysal 1 , Volkan Kilic 2 , Busra Korkut 1 , Seyda Ucarcan 2 , and Ozlem Atli 1 Background: Citalopram hydrobromide (CTL) has been shown to cause sexual dysfunction; however, its reproductive toxicity potential has not been sufficiently elucidated in men. Therefore, we aimed to clarify the toxic effects of CTL on the reproductive system of male rats. Methods: For this purpose, CTL was administered at 5, 10, and 20 mg/kg/day to rats orally for 28 days. Sperm concentration, motility, and morphology were investigated using a computer-assisted sperm analysis system, and sperm DNA damage was detected using a Comet assay. The testes were histopathologically examined. Serum follicle-stimulating hormone, luteinizing hormone, and testosterone levels were measured and the oxidative status of testes was investigated. Results: Our results showed that sperm concentration was reduced, and abnormal sperm morphology and sperm DNA damage were increased in CTL- administered groups. Additionally, histopathological changes were observed in the testes of CTL-administered rats. Luteinizing hormone levels were increased in CTL-administered groups, while testosterone levels were increased in the 5 and 10 mg/kg CTL-administered groups. Decreased glutathione signaled enhanced oxidative stress in the 10 and 20 mg/kg CTL- administered groups. Conclusion: Thus, we concluded that CT induced testicular damage in male rats; this testicular damage was accompanied by oxidative stress and hormonal changes, which are considered as the important causes of reproductive disorders. Birth Defects Research 00:000–000, 2017. V C 2017 Wiley Periodicals, Inc. Key words: citalopram; reproductive toxicity; oxidative stress; DNA damage Introduction Depression and anxiety are common public health problems that affect 5–10% of the world population (Mori et al., 2014; Wiegner et al., 2015). The World Health Organization notes that the annual prevalence of these diseases is between 4.6 and 26.4% (Verhaak et al., 2009). While the etiologies underlying depression and anxiety are still being researched, serotonin reuptake inhibitors (SSRI) are the most commonly prescribed drugs for treatment because of their efficacy, safety, and tolerability (Lee et al., 2011). Epi- demiological studies show that depression and anxiety often occur during the reproductive years, that is, ages between 20–60 (Wiegner et al., 2015). Thus, in the past decade, it has been hypothesized that drugs may have taken a role in the etiology of infertility, which affects 10 to 15% of the sexually active population, by affecting testicular functions in men (Alonso et al., 2009; Olayemi, 2010). It has been shown that SSRIs can cause sexually adverse effects, such as erectile dysfunction and low libido, and can affect emission and ejaculation in men (Tanrikut et al., 2010; Akasheh et al., 2014; Bijlsma et al., 2014). Studies have reported that SSRIs seem to have more of an effect on sperm transport rather than sperm production (Tanrikut and Schlegel, 2007; Attia and Bakheet, 2013). It has been observed in patients that sperm concentration, motility, and normal sperm morphology decrease and sperm DNA dam- age increases with SSRI treatment (Bataineh and Daradka, 2007; Tanrikut and Schlegel, 2007; Safarinejad, 2008; Tanrikut et al., 2010; Koyuncu et al., 2011, 2012; Relwani et al., 2011; Elnazer and Baldwin, 2014). Citalopram hydrobromide (CTL) is a commonly pre- scribed SSRI for the treatment of depression and anxiety, and according to 2011 data, it is the second most com- monly prescribed psychiatric medicine in the US, having been prescribed to 37.8 million people (Lindsley, 2012). Therefore, unlike the other studies performed previously, we evaluated sperm parameters, such as sperm DNA dam- age, sperm concentration, motility, and morphology, after CTL exposure at repeated pharmacological doses in the present study. In addition, a possible mechanism of action of the adverse reproductive effects was investigated by means of the determination of serum testosterone, follicle- stimulating hormone (FSH) and luteinizing hormone (LH) levels, which play roles in spermatogenesis process, and the determination of glutathione (GSH) and malondiald- hyde (MDA) levels for the oxidative status of testis tissue, which is extremely vulnerable to oxidative stress. Further- more, the dose-dependency of these possible toxic effects and the effects of biochemical alterations on testicular structure were evaluated. Materials and Methods MATERIALS CTL was a kind gift from IE Ulagay-Menarini Group, Istanbul, Turkey. Testosterone, FSH, LH, malondialdehyde (MDA), and glutathione (GSH) levels were determined using ELISA kits from Cusabio Biotech Co. Ltd. (Wuhan, China). 1 Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Eskisehir, Turkey 2 Anadolu University, Faculty of Science, Department of Biology, Eskisehir, Turkey *Correspondence to: Sinem Ilgin, Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Eskisehir, Turkey. E-mail: silgin@anadolu.edu.tr Published online 0 Month 2017 in Wiley Online Library (wileyonlinelibrary.com). Doi: 10.1002/bdr2.1010 V C 2017 Wiley Periodicals, Inc.