The role of antioxidant allagic acid in recovering spermatogenesis in a copper nanoparticles-injured rat model

Zahra Almasi,1,* Akbar vahdati,2 Mohsen forouzanfar,3 Mehrdad shariati,4

1. Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran
2. Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran
3. Department of Biology, Shiraz Branch, Islamic Azad University, Shiraz, Iran
4. Department of Biology, Kazeroon Branch, Islamic Azad University, Kazeroon, Iran



The fertility science has faced with major challenges for management of sperm disorder. nowadays, many water pollutants affect the male reproductive system, and common therapeutic methods often results in unsatisfactory results. there is an increasing interest in this topic (nanoreprotoxicity), due to the overall fertility decrease in industrialized countries, but there is still much to know concerning the effect of water pollutants on the reproductive system. nanoparticles (nps) are defined as particles between 1 and 100 nm in size (astm international), with unique size-dependent physical and chemical properties, compared with their larger counterparts (suh et al. 2009). metal nps play an increasing role in consumer products, biomedical applications and in the work environment (taylor et al. 2012). nps are capable of binding to cells as well as macromolecules like proteins and dna (asharani et al., 2009), subsequently, leading to alterations in dna integrity or affecting its synthesis and finally causing and affecting adverse health effects. elsewhere, nonspecific oxidative stress has been suggested as one of the greatest concern in nanoparticle-induced toxicity (nel et al., 2006). copper nanoparticles (cu-nps) are employed as antimicrobial and antifungal additives in water treatment, textiles, and paints (maisano et al., 2015). cu-nps toxicity in male reproduction has only been investigated in few studies. studies in vivo showed when such processes concern germline cells, the result may be altered spermatogenesis and fertility, subsequently affecting the reproduction rate and health of the offspring (ema et al., 2010). in a new study by gallo et al. (2018), performed on sea urchin, cu-nps exposure decreased spermatogenesis, impaired mitochondrial activity and increased the production of reactive oxygen species (ros) and lipid peroxidation. further understanding of natural antioxidant drugs and their effects on the reproductive system could help improving infertility treatments in patients. traditionally, antioxidant drugs could have commonly been used to treat free radicals, cellular process and tissue injured after inflammation and activation of cellular signalling processes by producing ros such as superoxide anion (o2-), hydrogen peroxide (h2o2), and/or hydroxyl radical (•oh). ellagic acid is a natural polyphenolic compound which has properties such as antioxidant activity to preventing lipid peroxidation and protecting germ cells from oxidative damage (pari and sivasankari, 2008; turk et al. 2008; najafi et al. 2018), by scavenging of free radicals and suppression of oxidative damage to dna (festa et al., 2001). since studies on the rat model and including cu-nps and sperm quality data are lacking, the present study was designed to investigate the effect of antioxidant ellagic acid on the recovery of spermatogenesis, histology and sexual hormones (fsh, lh and testosterone) in a cu-nps rat model.


Sixty adult rats were divided into six groups in a factorial arrangement of cu-nps and allagic acid treatments. rats received for 48 days a standard diet (controls), or a standard diet plus saline (sham). treatment groups orally received (1): 200 mg/kg cu-nps, (2): 50 mg/kg allagic acid, (3): 200 mg/kg cu-nps+10 mg/kg allagic acid and (4): 200 mg/kg cu-nps+50 mg/kg allagic acid. one day after the last treatment, spermatozoa were recovered from epididymis, blood was processed for sex hormones concentration (testosterone, fsh and lh) and testes were processed for histology.


The administration of cu-nps reduced testicular weight and volume, sex hormones concentration (testosterone and lh), the number of spermatogenic cells (including spermatogonia, spermatocytes, spermatids), and leydig cells in testis rats when compared to control (p<0.01). treated groups did not show significant changes in fsh concentration and sertoli cell count. administration of cu-nps with allagic acid significantly (p<0.01) reverted the spermatogenesis, hormonal levels and histology similar to controls, however not attaining the same sperm quality than controls


Cu-nps is clearly detrimental for spermatogenesis and overall testicular structure and function, whereas antioxidant allagic acid treatment improved testicular function and reverted cu-nps -induced azoospermia


Allagic acid, copper nanoparticles, rat, spermatogenesis, sex hormones