Low-dose gold nanoparticles exert subtle endocrine-modulating effects on the ovarian steroidogenic pathwayex vivoindependent of oxidative stress

Abstract

Gold nanoparticles (GNPs) have gained considerable attention for application in science and industry. However, the untoward effects of such particles on female fertility remain unclear. The objectives of the present study were to (1) examine the effects of 10-nm GNPs on progesterone and estradiol-17β accumulation by rat ovaries ex vivo and (2) to identify the locus/loci whereby GNPs modulate steroidogenesis via multiple-reference gene quantitative real-time RT-PCR. Regression analyses indicated a positive relationship between both Star (p<0.05, r2= 0.278) and Cyp11a1 (p<0.001, r2= 0.366) expression and P4 accumulation upon exposure to 1.43 × 106 GNPs/mL. Additional analyses showed that E2 accumulation was positively associated with Hsd3b1 (p<0.05, r2= 0.181) and Cyp17a1 (p<0.01, r2= 0.301) expression upon exposure to 1.43 × 103 and 1.43 × 109 GNPs/mL, respectively. These results suggest a subtle treatment-dependent impact of low-dose GNPs on the relationship between progesterone or estradiol-17β and specific steroidogenic target genes, independent of oxidative stress or inhibin.

Dose-dependent autophagic effect of titanium dioxide nanoparticles in human HaCaT cells at non-cytotoxic levels

“…However, the complexity of signalling means modulating autophagy with NPs could bring safety concerns. Earlier studies of NPs’ impact on cell systems suggest that dosage is a critical parameter in pathway modulation [ 37 , 38 ]. This type of study could deliver additional insights in enabling better safe-by-design strategies for NPs used in consumer products and/or in drug delivery therapy.…”

Nanoparticles Induced Oxidative Damage in Reproductive System and Role of Antioxidants on the Induced Toxicity

“…The potential harmful effects of nanoparticles such as induction of cellular states of oxidative stress, modulation of enzyme activity, inflammation, and cell death include disruption of gonadal steroidogenesis-related biochemical and physiologic processes [ 16 ]. Larson et al [ 76 ] reported that gold nanoparticles could be a new class of ovarian endocrine-inhibiting compounds if exposed for extended periods or at high concentrations as they disrupt the production of sex-steroid hormones, resulting in reproductive problems in humans and animals [ 76 ]. By contrast, Gallus domesticus treated with silver nanoparticles showed no significant differences in progesterone levels between the granulosa and theca layers, but a progressive reduction in estradiol and testosterone levels was observed in theca cells.…”

Ex vivodetection and quantification of gold nanoparticles in human seminal and follicular fluids

“…17 As revealed by an ex vivo study on rat ovaries, nanoparticles can still exert noxious effects by disrupting the secretion and bioavailability of endocrine molecules even if they do not physically interact with the oocyte as just tens of particles of 10 nm Au particles were capable of significantly altering the biosynthesis of steroid hormones. 18 The available literature suggests that nanoparticles have the potential to jeopardise the normal function of the male and female reproductive system. Despite these alarming signs, there are no clinical studies to explore the potential risk in fertility and fecundity posed by human exposure to engineered nanoparticles.…”