Low-dose gold nanoparticles exert subtle endocrine-modulating effects on the ovarian steroidogenic pathway ex vivo independent 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 this 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 × 1³ 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.

Keywords::

• nanotoxicology
• genomics

Acknowledgments

We thank R. Klaper for allowing our use of the Malvern Zeta-sizer Nano Z, Q. Liu for his assistance with molecular techniques, and D. Arndt for acquisition of the SEM micrographs. We express sincere gratitude to J. Ghorai and P. Dunn for their advice on statistical analyses. We thank H. Owen for his advice on imaging strategies. We thank M. Gajdardziska-Josifovska, M. Schofield and D. Robertson for their collaborative acquisition of high-resolution TEM micrographs. We also thank M. Engelhard of the Environmental Molecular Sciences Laboratory (EMSL) at Pacific Northwest National Laboratory, for characterizing our GNPs via X-ray photoelectron spectroscopy. This research was supported by the Children's Environmental Health Sciences Core Center at the University of Wisconsin–Milwaukee and Children's Research Institute (NIEHS P30 ES004184 PRJ32IR).