Public concern regarding environmental hazards is perhaps greatest when potential exposures are related to reproductive health 29. TCS is an environmental contaminant of emerging concern because of its presence in a wide variety of personal care and household products, as well as in the ecosystem and in human body fluids. TCS has been subjected to several toxicological studies; yet, little information is currently available concerning its adverse effects on the reproductive system 30,31. Moreover, the highly sensitive cellular composition of the spermatogenic epithelium makes the testis more vulnerable to environmental hazards compared with other tissues. A research work concerned with treatment of male infertility problems has issued the existence of a link between the antioxidant-rich PJ and male fertility 23. Therefore, the study aimed to histologically clarify the possible testicular alterations that might occur in the STs of adult rats following TCS administration, as well as the possible protective role of PJ coadministration.
The steroidogenic acute regulatory (StAR) protein is a factor that plays a crucial role in regulating steroidogenesis by transporting cholesterol to the inner mitochondrial membrane for its utilization by steroidogenic enzymes. Kumar et al. 13 further reported a decreased transcription and translation of StAR in the testis following TCS administration. They attributed such alteration to the decreased level of serum LH as it simulates steroidogenesis mostly by regulating the level and activity of StAR protein in steroidogenic cells. In addition, TCS may have direct effects on mitochondria, impairing its function through an uncoupler effect and disrupting mitochondrial membrane fluidity. Besides, it directly affects ATP, causing a significant inhibition of the enzyme activity, considering the results obtained with disrupted mitochondria 38.
There is evidence that TCS can influence the endocrine function indirectly through effects on the metabolism of key hormones, including thyroid hormones, because it chemically mimics the thyroid hormone 7. Earlier studies have demonstrated that TCS exposure decreases thyroid hormone concentrations in a dose-dependent manner 5,12. Evidence suggests that TCS upregulates phase II glucuronidation and sulfation of thyroid hormones in the liver, enhancing their catabolism that results in hypothyroxinemia 44,45. Thus, testicular alterations induced by TCS could be attributed, at least in part, to disruption of thyroid hormone homeostasis.
Pomegranate and its constituents have been consumed for centuries without adverse effects. In the present work, rats of group II that received PJ alone did not show any significant changes in serum testosterone levels, or in the histological or histomorphometric characteristics of the STs, compared with the control group. These results are consistent with previous studies that have postulated that pomegranate, in various forms, can be included as part of a healthy lifestyle with no risk of toxic reactions 46. In the USA, the Food and Drug Administration has approved pomegranate as Generally Recognized as Safe 47. Research in human volunteers has demonstrated the safety of pomegranate extract in amounts up to 1420 mg/day (870 mg gallic acid equivalents) for 28 days, with no adverse effects 48. Another study in patients with carotid artery stenosis demonstrated that PJ consumption (121 mg/l ellagic acid equivalents) for up to 3 years has no toxic effect 49. In addition, punicalagin has been proved to have no toxic effect in rats as confirmed by histological examination of rat organs 50.
Concomitant administration of PJ with TCS for 60 days was associated with preservation of the histological and histomorphometric characteristics of most of the STs that retained their normal epithelial stratification. Such prevailed improvement was further supported by the significant increase in serum testosterone levels as compared with TCS (group III)-treated rats, indicating the protection of Leydig cells as well.
Pomegranate has been revered as a symbol of fertility by several civilizations, and today modern science is validating this belief. Several researchers have pointed out an improvement in epididymal sperm concentration and motility, germ cell layer thickness, and diameter of STs in nonstressed healthy laboratory animals following pomegranate administration 23,51. In addition, in-vitro PJ supplementation to rooster’s semen improves sperm motility, viability, and acrosomal integrity during cool storage 52. Moreover, PJ and pomegranate extracts have been reported to ameliorate spermatogenic disruption and damage in sperm quality associated with OS, induced by lead acetate 53. Similarly, Abdou et al. 54 have demonstrated that pomegranate peels and seeds decrease carbon tetrachloride-induced sperm shape abnormalities.
A wealth of evidence indicates high antioxidant and free radical scavenging capacity of PJ attributable mainly to its protective effects 52,55. Its antioxidant activity is considered the highest among most of the plants, and this is mostly attributed to its rich polyphenolic content, mainly ellagic acid and punicalagin 53. In such a context, several studies have postulated a modulatory effect of ellagic acid on OS-induced male reproductive dysfunction in experimental animals, thus improving male fertility. This is indicated by increased epididymal sperm concentration, glutathione, glutathione peroxidase, and catalase activities along with improvement in the testicular histological view 56,57. In addition, quercetin, which has been shown to be a component in pomegranate, is reported to improve sperm quality 53.
The powerful antioxidants in pomegranate act by boosting the levels of glutathione, which helps to protect DNA in the cells from free radical damage. After oral intake of PJ, the antioxidant enzymatic activities (catalase and glutathione peroxidase) increase, whereas lipid peroxidation (malondialdehyde level) decreases 23. PJ further increases the enzymes that protect LDL and HDL from oxidation 23,58.
Evidence suggests that PJ and vitamin C increase the production of natural antioxidants in the sperm and blood of rats, which probably protects the vulnerable fatty acids against oxidation 23,64. Again, vitamin C is known to support spermatogenesis at least, in part, through its capacity to stimulate both sperm production and testosterone secretion 64.
Overall, the results of this work reinforce the notion that TCS poses a hazard to male reproductive health; therefore, it would be wise to restrict its use. Furthermore, the results recommend PJ as a good remedy and nontoxic adjunct against male reproductive dysfunction. Additional studies are needed to more fully characterize the effect of TCS on the hypothalamic–pituitary–gonadal axis, as well as the potential adverse health outcomes of these changes.
There are no conflicts of interest.
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