The effects of gold nanoparticles on Leydig cells and male reproductive function in mice

Abstract

Background: Gold nanoparticles (AuNPs) have shown great promise in various biomedical applications, but their effects on male reproductive function remain to be ascertained. The aim of this study was to investigate the uptake, cytotoxicity and testosterone production inhibition of AuNPs in mouse Leydig cells, as well as their accumulation in the testes of male mice and their effects on male reproductive function.Results: AuNPs (5 nm) were able to be internalized into the endosomes/lysosomes of TM3 Leydig cells, induce the formation of autophagosomes, increase the production of reactive oxygen species (ROS), and arrest the cell cycle in S phase, resulting in concentration-dependent cytotoxicity and DNA damage. Interestingly, AuNPs significantly reduced testosterone production in TM3 cells by inhibiting the expression of 17α-hydroxylase, an important enzyme in androgen synthesis. After repeated intravenous injection, AuNPs gradually accumulated and retained in the testes of male BALB/c mice in a dose-dependent manner. One week after withdrawal, the level of plasma testosterone in the 0.5 mg/kg AuNPs group was significantly reduced compared to that in the PBS control group, accompanied by the decreased expression of 17α-hydroxylase in the testes. In addition, AuNPs treatment significantly increased the rate of epididymal sperm malformation, but without affecting fertility.Conclusion: Our results suggest that AuNPs can accumulate in the testes and reduce testosterone production in Leydig cells by down-regulating the expression of 17α-hydroxylase, thus affecting the quality of epididymal sperm.

The potential for nanomaterial toxicity affecting the male reproductive system

“…Most metal or metal oxide NMs smaller than 100 nm can cross the Sertoli cell barrier; however, the other properties of the nanomaterials are also important to their behavior. For example, gold nanoparticles (AuNPs), silver nanoparticles (AgNPs), carbon nanotubes, nano‐silica (SiO 2 NPs), Zinc oxide nanoparticles (ZnO NPs), and cerium oxide nanoparticles (CeO 2 NPs) all can enter the testes, while Au, Ag, titanium oxide (TiO 2 NPs), and CeO 2 NPs tend to accumulate in the testes (Ge et al, 2012; Li et al, 2012, 2020; Liu, Li, et al, 2020; Lu et al, 2019; Meena et al, 2015; Morishita et al, 2012; Qin et al, 2019; Zande et al, 2012). Unlike the blood–brain barrier, no pathway has been shown to bypass the Sertoli cell barrier in order for entry into the seminiferous tubules.…”

“…Testicular biopersistence of NMs seems to depend on their exposure route. AuNPs have been shown to accumulate in the testes in a dose‐dependent manner, remaining there for at least 1 week (Liu, Li, et al, 2020). Male BALB/c mice injected intravenously (IV) with phosphate‐buffered saline (PBS) served as a control, while 0.17 mg/kg AuNPs or 0.50 mg/kg AuNPs once a day for 14 consecutive days were provided to the experimental groups, of which the 0.50 mg/kg group exhibited the presence of significant amounts of AuNPs in the testicular tissue.…”

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

“…The integrity of BTB is a concern since NPs can easily permeate cells and their nuclei. This creates favorable circumstances for mutations appearance, which in germ cells may interfere with fertilization, embryogenesis [ 100 ], or even generate congenital defects in the offspring [ 101 ].…”

Toxicity mechanisms of nanoparticles in the male reproductive system

“…EDCs disrupt the body's normal function due to their ability to block or mimic a hormone's natural function (Dagar and Bagchi 2020). A study has shown that AuNPs can accumulate in the testes and decrease testosterone production in Leydig cells via a decrease the expression of 17a-hydroxylase, consequently affecting the quality of epididymal sperm (Liu et al 2020). NPs can also affect spermatogenesis and sex hormones levels and potential of spermatozoa, so influencing fertility.…”