Resumption of meiotic maturation of oocytes, pre- and post-implantation mortality of embryos under ten-time intravenous treatment of silver nanoparticles in mice

Valentyna O. Sribna, Oksana N. Kaleynykova, Natalia G. Grushka, Taras V. Blashkiv, Tetyana Yu. Voznesenska, Roman I. Yanchiy


Background: In recent years the use of silver nanoparticles (AgNP) has increased significantly being focused on assessing human health and environmental risks of nanotechnology.

Methods: Research (two series) has been done on white laboratory mice. One dose (20 mg/kg) has been investigated. Frequency of treatment: one time per day for 10 times. Material for the study (ovaries, tubes and uterus) was taken under anesthetic anesthesia on the 10/11th, 21/22nd, 33/34th, 42/43rd days (after the last treatment). Oocyte meiotic maturation, pre- and post-implantation mortality of embryos under ten-time intravenous treatment of AgNP were investigation.

Results: Under the ten-time treatment of AgNPs, the inhibition of reproductive function in female mice occurs: a decrease in the number and quality of ovarian oocytes; after male mice were planted, the females do not get pregnant to 21/22 day. The reproductive function in experimental animals is restored on the 40th day after the last treatment with AgNPs; there is no differences between the values of pre- and post-implantation mortality of embryos on the 33/34th day after male mice were planted; in one of the three experimental animals, 7 live pups were born on the 42/43rd day after the male was planted (in animals of the control group during this period: twice (6 ± 1 (n = 6) live pups).

Conclusions: In mice females, under a ten-time treatment of AgNPs, the inhibition of reproductive function takes place; with the termination of the AgNPs treatment, the reproductive function is restored.


Embryos, Nanoparticles, Oocytes

Full Text:



Alshehri AH, Jakubowska M, Młożniak A, Horaczek M, Rudka D, Free C, et al. Enhanced electrical conductivity of silver nanoparticles for high frequency electronic applications. ACS Appl Mater Interface. 2012;4(12):7007-10.

Chen G, Lu J, Lam C, Yu Y. A novel green synthesis approach for polymer nanocomposites decorated with silver nanoparticles and their antibacterial activity. Analyst. 2014;21;139(22):5793-9.

Braun GB, Friman T, Pang HB, Pallaoro A, Hurtado de Mendoza T, Willmore AM, et al. Etchable plasmonic nanoparticle probes to image and quantify cellular internalization. Nat Mater. 2014;13(9):904-11.

Chernousova S, Epple M. Silver as antibacterial agent: ion, nanoparticle, and metal. Angew Chem Int Ed Engl. 2013;52(6):1636-53.

Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J. 2008;22(3):659-61.

Park K, Park EJ, Chun IK, Choi K, Lee SH, Yoon J, et al. Bioavailability and toxicokinetics of citrate-coated silver nanoparticles in rats. Arch Pharm Res. 2011;34(1):153-8.

Xue Y, Zhang S, Huang Y, Zhang T, Liu X, Hu Y, et al. Acute toxic effects and gender-related biokinetics of silver nanoparticles following an intravenous injection in mice. J Appl Toxicol. 2012;32(11):890-9.

De Jong WH, Van Der Ven LT, Sleijffers A, Park MV, Jansen EH, Van Loveren H, et al. Systemic and immunotoxicity of silver nanoparticles in an intravenous 28 days repeated dose toxicity study in rats. Biomaterial 2013;34(33):8333-43.

Rigo C, Ferroni L, Tocco I, Roman M, Munivrana I, Gardin C, et al. Active silver nanoparticles for wound healing. Int J Mol Sci. 2013;14(3):4817-40.

Wei L, Lu J, Xu H, Patel A, Chen Z, Chen G. Silver nanoparticles: synthesis, properties, and therapeutic applications. Drug Discov Today. 2015;20(5):595-601.

van der Zande M, Vandebriel R, Van Doren E, Kramer E, Herrera Rivera Z, Serrano-Rojero C, et al. Distribution, elimination, and toxicity of silver nanoparticles and silver ions in rats after 28-day oral exposure. ACS Nano. 2012;6(8):7427-42.

Kwon J, Minai-Tehrani A, Hwang S, Kim J, Shin J, Yu K, et al.Acute pulmonary toxicity and body distribution of inhaled metallic silver nanoparticles. Toxicol Res. 2012;28(1):25-31.

Recordati C, De Maglie M, Bianchessi S, Argentiere S, Cella C, Mattiello S, et al. Tissue distribution and acute toxicity of silver after single intravenous administration in mice: nano-specific and size-dependent effects. Part Fibre Toxicol. 2016; 29(13):12.

Li P, Kuo T, Chang J, Yeh J, Chan W. Induction of cytotoxicity and apoptosis in mouse blastocysts by silver nanoparticles. Toxicol Lett. 2010;197(2):82-7.

Taylor U, Garrels W, Barchanski A, Peterson S, Sajti L, Lucas-Hahn A, et al. Injection of ligand-free gold and silver nanoparticles into murine embryos does not impact pre-implantation development. Beilstein J Nanotechnol. 2014;21(5):677-88.

Yu W, Son J, Lee J, Kim S, Lee I, Baek H, et al. Effects of silver nanoparticles on pregnant dams and embryo-fetal development in rats. Nanotoxicol 2014;8(1):85-91.

Lytvynenko A, Rieznichenko L, Sribna V, Stupchuk M, Grushka N, Shepel A, et al. Functional status of reproductive system under treatment of silver nanoparticles in female mice. Int J Reproduct Contracep Obstet Gynecol. 2017;6(5):1713-20.

Johnston H, Hutchison G, Christensen F, Peters S, Hankin S, Stone V. A review of the in vivo and in vitro toxicity of silver and gold particulates: particle attributes and biological mechanisms responsible for the observed toxicity. Crit Rev Toxicol. 2010;40(4): 328-46.

Tiedemann D, Taylor U, Rehbock C, Jakobi J, Klein S, Kues W, et al. Reprotoxicity of gold, silver, and gold-silver alloy nanoparticles on mammalian gametes. Analyst 2014;139(5):931-42.

Taylor U, Tiedemann D, Rehbock C, Kues W, Barcikowski S, Rath D. Influence of gold, silver and gold-silver alloy nanoparticles on germ cell function and embryo development. Beilstein J Nanotechnol 2015;5(6):651-64.

Durán N, Durán M, de Jesus M, Seabra A, Fávaro W, Nakazato G. Silver nanoparticles: A new view on mechanistic aspects on antimicrobial activity. Nanomed. 2016;12(3):789-99.

Hsin Y, Chen C, Huang S, Shih T, Lai P, Chueh P. The apoptotic effect of nanosilver is mediated by a ROS- and JNK-dependent mechanism involving the mitochondrial pathway in NIH3T3 cells. Toxicol Lett. 2008;179(3):130-9.

Laban G, Nies L, Turco R, Bickham J, Sepúlveda M. The effects of silver nanoparticles on fathead minnow (Pimephalespromelas) embryos. Ecotoxicol. 2010;19(1):185-95.

Choi J, Kim S, Ahn J, Youn P, Kang J, Park K, et al. Induction of oxidative stress and apoptosis by silver nanoparticles in the liver of adult zebrafish. Aquat Toxicol. 2010;100(2):151-9.

Maillard J, Hartemann P. Silver as an antimicrobial: facts and gaps in knowledge. Crit Rev Microbiol. 2013;39(4):373-83.