Metal Oxide Nanoparticles: Evidence of Adverse Effects on the Male Reproductive System

Abstract

Metal oxide nanoparticles (MONPs) are inorganic materials that have become a valuable tool for many industrial sectors, especially in healthcare, due to their versatility, unique intrinsic properties, and relatively inexpensive production cost. As a consequence of their wide applications, human exposure to MONPs has increased dramatically. More recently, their use has become somehow controversial. On one hand, MONPs can interact with cellular macromolecules, which makes them useful platforms for diagnostic and therapeutic interventions. On the other hand, research suggests that these MONPs can cross the blood–testis barrier and accumulate in the testis. Although it has been demonstrated that some MONPs have protective effects on male germ cells, contradictory reports suggest that these nanoparticles compromise male fertility by interfering with spermatogenesis. In fact, in vitro and in vivo studies indicate that exposure to MONPs could induce the overproduction of reactive oxygen species, resulting in oxidative stress, which is the main suggested molecular mechanism that leads to germ cells’ toxicity. The latter results in subsequent damage to proteins, cell membranes, and DNA, which ultimately may lead to the impairment of the male reproductive system. The present manuscript overviews the therapeutic potential of MONPs and their biomedical applications, followed by a critical view of their potential risks in mammalian male fertility, as suggested by recent scientific literature.

ALKBH5 in mouse testicular Sertoli cells regulates Cdh2 mRNA translation to maintain blood–testis barrier integrity

“…Cumulative studies have shown that some adverse factors, such as new coronavirus [36], Marburg virus [37], chemotherapeutic drug busulfan [38], and heavy metal ion cadmium [39], can damage the BTB, resulting in spermatogenesis disorder and even male infertility. In addition, some studies have shown that some substances, such as manganese [40], nicotine and its metabolites in tobacco smoke [41], and metal oxide nanoparticles [42], can directly pass through the BTB and cause spermatogenesis disorder. Therefore, maintaining BTB integrity is an important basis for normal spermatogenesis.…”

Palliative Effect of Resveratrol against Nanosized Iron Oxide-Induced Oxidative Stress and Steroidogenesis-Related Genes Dysregulation in Testicular Tissue of Adult Male Rats

“…For instance, Nr5A1 is a transcription factor that regulates the expression of steroidogenic genes like 3β-HSD in Leydig cells. Hence, some authors explored the influence of metal oxide NPs on the expression of genes related to steroidogenesis [99]. For instance, Hussein et al [100] reported that the intragastric administration of zinc oxide NPs (100 and 400 mg/kg b.wt) for 12 weeks significantly downregulated the expression of 17β-HSD, 3β-HSD, and Nr5A1 and simultaneously reduced the TES level.…”

Safety and Toxicity Implications of Multifunctional Drug Delivery Nanocarriers on Reproductive Systems In Vitro and In Vivo

“…Furthermore, the effects of direct mixing of the PVA (polyvinyl alcohol)-coated iron oxide nanoparticles with the sperm samples obtained from bovine were analyzed. When nanoparticles are reported to be entering the spermatozoid cells and then could get attached to their mitochondrial organelles inside their tails and also in their acrosomal regions inside their heads, there have been no direct impacts on spermatozoid acrosomal reactions and motilities ( Vassal et al, 2021 ).…”