1. bookVolume 55 (2021): Issue 1 (January 2021)
Journal Details
First Published
30 Mar 2016
Publication timeframe
4 times per year
access type Open Access

Plant isoflavones can affect accumulation and impact of silver and titania nanoparticles on ovarian cells

Published Online: 29 Jan 2021
Volume & Issue: Volume 55 (2021) - Issue 1 (January 2021)
Page range: 52 - 60
Journal Details
First Published
30 Mar 2016
Publication timeframe
4 times per year

Objectives. The application of nanoparticles is experiencing a rapid growth, but it faces a problem of their toxicity, especially adverse effects on female reproduction. Food and medicinal plants and their isoflavones can be protectors against environmental stressors, but their ability to abate the adverse effects of nanoparticles has not been studied yet. In the present study, we examined the effect of silver (AgNPs) and titanium dioxide (titania, TiO2NPs) nanoparticles alone or in combination with plant phytoestrogens/antioxidants (resveratrol, diosgenin, and quercetin) on accumulation of nanoparticles, and progesterone release by cultured porcine ovarian granulosa cells.

Methods. Porcine granulosa cells were incubated in the presence of AgNPs or TiO2NPs (0.1, 1, 10 or 100 µg/ml) alone or in combination with resveratrol, diosgenin or quercetin (10 µg/ml) for 48 h. The accumulation of tested nanoparticles by granulosa cells was assessed under light microscope. Progesterone concentration in culture media was measured by ELISA kit.

Results. Cells accumulated both AgNPs and TiO2NPs in a dose-dependent manner. AgNPs, but not TiO2NPs, at highest dose (100 µg/ml) resulted in a destruction of cell monolayer. Both Ag-NPs and TiO2NPs reduced progesterone release. Resveratrol, diosgenin, and quercetin promoted accumulation of both AgNPs and TiO2NPs in ovarian cells and inhibited the progesterone output. Furthermore, resveratrol and diosgenin, but not quercetin, prevented the suppressive action of both AgNPs, and TiO2NPs on progesterone release.

Conclusions. These observations (1) demonstrate accumulation of AgNPs and TiO2NPs in ovarian cells, (2) confirm the toxic impact of AgNPs, and TiO2NPs on these cells, (3) confirm the inhibitory effects of plant polyphenols/phytoestrogens on ovarian steroidogenesis, (4) show the ability of these isoflavones to increase the accumulation of AgNPs and TiO2NPs, and (5) show their ability to reduce the suppressive effect of AgNPs and TiO2NPs on ovarian progesterone release. The suppressive effect of AgNPs and TiO2NPs on ovarian functions should be taken into account by their exposition. However, these adverse effects could be mitigated by some plant isoflavones.


Almeida IM, Rodrigues F, Sarmento B, Alves RC, Oliveira MB. Isoflavones in food supplements: chemical profile, label accordance and permeability study in Caco-2 cells. Food Funct 6, 938–946, 2015.10.1039/C4FO01144A Search in Google Scholar

Atlante A, Bobba A, Paventi G, Pizzuto R, Passarella S. Genistein and daidzein prevent low potassium-dependent apoptosis of cerebellar granule cells. Biochem Pharmacol 79, 758–767, 2010.10.1016/j.bcp.2009.10.00519822130 Search in Google Scholar

Banu SK, Stanley JA, Sivakumar KK, Arosh JA, Burghardt RC. Resveratrol protects the ovary against chromium-toxicity by enhancing endogenous antioxidant enzymes and inhibiting metabolic clearance of estradiol. Toxicol Appl Pharmacol 303, 65–78, 2016.10.1016/j.taap.2016.04.016583008527129868 Search in Google Scholar

Baranowska-Wojcik E, Szwajgier D, Oleszczuk P, Winiarska-Mieczan A. Effects of titanium dioxide nanoparticles exposure on human health - a review. Biol Trace Elem Res 193, 118–129, 2020.10.1007/s12011-019-01706-6691471730982201 Search in Google Scholar

Beazley KE, Nurminskaya M. Effects of dietary quercetin on female fertility in mice: implication of transglutaminase 2. Reprod Fertil Dev 28, 974–981, 2016.10.1071/RD14155479443525557047 Search in Google Scholar

Bodis J, Sulyok E, Koszegi T, Godony K, Premusz V, Varnagy A. Serum and follicular fluid levels of sirtuin 1, sirtuin 6, and resveratrol in women undergoing in vitro fertilization: an observational, clinical study. J Int Med Res 47, 772–782, 2019.10.1177/0300060518811228638145330556451 Search in Google Scholar

Brohi RD, Wang L, Talpur HS, Wu D, Khan FA, Bhattarai D, Rehman ZU, Farmanullah F, Huo LJ. Toxicity of nanoparticles on the reproductive system in animal models: a review. Front Pharmacol 8, 606, 2017.10.3389/fphar.2017.00606559188328928662 Search in Google Scholar

De Matteis V, Cascione M, Toma CC, Leporatti S. Silver nanoparticles: synthetic routes, in vitro toxicity and theranostic applications for cancer disease. Nanomaterials (Basel) 8, 319, 2018.10.3390/nano8050319597733329748469 Search in Google Scholar

Di Virgilio AL, Reigosa M, Arnal PM, Fernandez Lorenzo de Mele M. Comparative study of the cytotoxic and genotoxic effects of titanium oxide and aluminium oxide nanoparticles in Chinese hamster ovary (CHO-K1) cells. J Hazard Mater 177, 711–718, 2010.10.1016/j.jhazmat.2009.12.08920079968 Search in Google Scholar

Feranchak AP, Kilic G, Wojtaszek PA, Qadri I, Fitz JG. Volume-sensitive tyrosine kinases regulate liver cell volume through effects on vesicular trafficking and membrane Na+ permeability. J Biol Chem 278, 44632–44638, 2003.10.1074/jbc.M30195820012939281 Search in Google Scholar

Flores-Lopez LZ, Espinoza-Gomez H, Somanathan R. Silver nanoparticles: Electron transfer, reactive oxygen species, oxidative stress, beneficial and toxicological effects. Mini review. J Appl Toxicol 39, 16–26, 2019.10.1002/jat.365429943411 Search in Google Scholar

Gao G, Ze Y, Li B, Zhao X, Zhang T, Sheng L, Hu R, Gui S, Sang X, Sun Q, Cheng J, Cheng Z, Wang L, Tang M, Hong F. Ovarian dysfunction and gene-expressed characteristics of female mice caused by long-term exposure to titanium dioxide nanoparticles. J. Hazard. Mater 243, 19–27, 2012.10.1016/j.jhazmat.2012.08.04923131501 Search in Google Scholar

Grande F, Tucci P. Titanium dioxide nanoparticles: a risk for human health? Mini Rev Med Chem 16, 762–769, 2016.10.2174/138955751666616032111434126996620 Search in Google Scholar

Han JW, Jeong JK, Gurunathan S, Choi YJ, Das J, Kwon DN, Cho SG, Park C, Seo HG, Park JK, Kim JH. Male-and female-derived somatic and germ cell-specific toxicity of silver nanoparticles in mouse. Nanotoxicology 10, 361–373, 2016.10.3109/17435390.2015.107339626470004 Search in Google Scholar

Hill EK, Li J. Current and future prospects for nanotechnology in animal production. J Animal Sci Biotechnol 8, 26, 2017.10.1186/s40104-017-0157-5535105428316783 Search in Google Scholar

Hong F, Wang L. Nanosized titanium dioxide-induced premature ovarian failure is associated with abnormalities in serum parameters in female mice. Int J Nanomedicine 13, 2543–2549, 2018.10.2147/IJN.S151215592735429731629 Search in Google Scholar

Hou J, Wan XY, Wang F, Xu GF, Liu Z [Effects of titanium dioxide nanoparticles on development and maturation of rat preantral follicle in vitro]. Acad J Second Mil Med Univ 30, 869–873, 2009.10.3724/SP.J.1008.2009.00869 Search in Google Scholar

Jahan S, Abid A, Khalid S, Afsar T, Qurat-Ul-Ain, Shaheen G, Almajwal A, Razak S. Therapeutic potentials of Quercetin in management of polycystic ovarian syndrome using Letrozole induced rat model: a histological and a biochemical study. J Ovarian Res 11, 26, 2018.10.1186/s13048-018-0400-5588360729615083 Search in Google Scholar

Jozkowiak M, Hutchings G, Jankowski M, Kulcenty K, Mozdziak P, Kempisty B, Spaczynski RZ, Piotrowska-Kemp-isty H. The stemness of human ovarian granulosa cells and the role of resveratrol in the differentiation of MSCs-A review based on cellular and molecular knowledge. Cells 9, 1418, 2020.10.3390/cells9061418734918332517362 Search in Google Scholar

Jungbauer A, Medjakovic S. Phytoestrogens and the metabolic syndrome. J Steroid Biochem Mol Biol 139, 277–289, 2014.10.1016/j.jsbmb.2012.12.00923318879 Search in Google Scholar

Kim S, Lim YT, Soltesz EG, De Grand AM, Lee J, Nakayama A, Parker JA, Mihaljevic T, Laurence RG, Dor DM, Cohn LH, Bawendi MG, Frangioni JV. Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat Biotechnol 22, 93–97, 2004.10.1038/nbt920234661014661026 Search in Google Scholar

Li N, Sun C, Zhou B, Xing H, Ma D, Chen G, Weng D. Low concentration of quercetin antagonizes the cytotoxic effects of anti-neoplastic drugs in ovarian cancer. PLoS One 9, e100314, 2014.10.1371/journal.pone.0100314408506624999622 Search in Google Scholar

Liu Y, Wang YL, He SW, Chen MH, Zhang Z, Fu XP, Fu BB, Liao BQ, Lin YH, Qi ZQ, Wang HL. Protective effects of resveratrol against mancozeb induced apoptosis damage in mouse oocytes. Oncotarget 8, 6233–6245, 2017.10.18632/oncotarget.14056535162728031523 Search in Google Scholar

Mikhailov OV, Mikhailova EO. Elemental Silver nanoparticles: biosynthesis and bio applications. Materials (Basel) 12, 3177, 2019.10.3390/ma12193177680399431569794 Search in Google Scholar

Nawaz W, Zhou Z, Deng S, Ma X, Ma X, Li C, Shu X. Therapeutic versatility of resveratrol derivatives. Nutrients 9, 1188, 2017.10.3390/nu9111188570766029109374 Search in Google Scholar

Ortega I, Villanueva JA, Wong DH, Cress AB, Sokalska A, Stanley SD, Duleba AJ. Resveratrol reduces steroidogenesis in rat ovarian theca-interstitial cells: the role of inhibition of Akt/PKB signaling pathway. Endocrinology 153, 4019–4029, 2012.10.1210/en.2012-1385340435422719052 Search in Google Scholar

Ozatik FY, Ozatik O, Yigitaslan S, Kaygisiz B, Erol K. Do resveratrol and dehydroepiandrosterone increase diminished ovarian reserve? Eurasian J Med 52, 6–11, 2020.10.5152/eurasianjmed.2019.19044705123132158305 Search in Google Scholar

Podolak I, Galanty A, Sobolewska D. Saponins as cytotoxic agents: a review. Phytochem Rev 9, 425–474, 2010.10.1007/s11101-010-9183-z292844720835386 Search in Google Scholar

Rietjens IMCM, Louisse J, Beekmann K. The potential health effects of dietary phytoestrogens. Br J Pharmacol 174, 1263–1280, 2017.10.1111/bph.13622542933627723080 Search in Google Scholar

Said RS, El-Demerdash E, Nada AS, Kamal MM. Resveratrol inhibits inflammatory signaling implicated in ionizing radiation-induced premature ovarian failure through antagonistic crosstalk between silencing information regulator 1 (SIRT1) and poly(ADP-ribose) polymerase 1 (PARP-1). Biochem Pharmacol 103, 140–150, 2016.10.1016/j.bcp.2016.01.01926827941 Search in Google Scholar

Said RS, Mantawy EM, El-Demerdash E. Mechanistic perspective of protective effects of resveratrol against cisplatin-induced ovarian injury in rats: emphasis on anti-inflammatory and anti-apoptotic effects. Naunyn Schmiedebergs Arch Pharmacol 392, 1225–1238, 2019.10.1007/s00210-019-01662-x31129703 Search in Google Scholar

Santini SE, Basini G, Bussolati S, Grasselli F. The phytoestrogen quercetin impairs steroidogenesis and angiogenesis in swine granulosa cells in vitro. J Biomed Biotechnol 2009, 419891, 2009.10.1155/2009/419891269393219704917 Search in Google Scholar

Sirotkin AV. Regulators of ovarian functions, second ed., Nova Science Publishers, Inc New York, 2014. Search in Google Scholar

Sirotkin AV, Harrath AH. Phytoestrogens and their effects. Eur J Pharmacol 741, 230–236, 2014.10.1016/j.ejphar.2014.07.05725160742 Search in Google Scholar

Sirotkin AV, Alexa R, Alwasel S, Harrath AH. The phytoestrogen, diosgenin, directly stimulates ovarian cell functions in two farm animal species. Domest Anim Endocrinol 69, 35–41, 2019.10.1016/j.domaniend.2019.04.00231280024 Search in Google Scholar

Tarko A, Stochmalova A, Hrabovszka S, Vachanova A, Harrath AH, Alwasel S, Grossman R, Sirotkin AV. Can xylene and quercetin directly affect basic ovarian cell functions? Res Vet Sci 119, 308–312, 2018.10.1016/j.rvsc.2018.07.01030086515 Search in Google Scholar

Tarko A, Stochmalova A, Jedlickova K, Hrabovszka S, Vachanova A, Harrath AH, Alwasel S, Alrezaki A, Kotwica J, Balazi A, Sirotkin AV. Effects of benzene, quercetin, and their combination on porcine ovarian cell proliferation, apoptosis, and hormone release. Arch Anim Breed 62, 345–351, 2019.10.5194/aab-62-345-2019685286231807645 Search in Google Scholar

van Duursen MBM. Modulation of estrogen synthesis and metabolism by phytoestrogens in vitro and the implications for women‘s health. Toxicol Res (Camb) 6, 772–794, 2017.10.1039/c7tx00184c606238230090542 Search in Google Scholar

Volkovova K, Handy RD, Staruchova M, Tulinska J, Kebis A, Pribojova J, Ulicna O, Kucharska J, Dusinska M. Health effects of selected nanoparticles in vivo: liver function and hepatotoxicity following intravenous injection of titanium dioxide and Na-oleate-coated iron oxide nanoparticles in rodents. Nanotoxicology 9 (Suppl 1), 95–105, 2015.10.3109/17435390.2013.81528523763576 Search in Google Scholar

Wu M, Ma L, Xue L, Ye W, Lu Z, Li X, Jin Y, Qin X, Chen D, Tang W, Chen Y, Hong Z, Zhang J, Luo A, Wang S. Resveratrol alleviates chemotherapy-induced oogonial stem cell apoptosis and ovarian aging in mice. Aging (Albany NY) 11, 1030–1044, 2019.10.18632/aging.101808638241830779707 Search in Google Scholar

Zhang J, Chen Q, Du D, Wu T, Wen J, Wu M, Zhang Y, Yan W, Zhou S, Li Y, Jin Y, Luo A, Wang S. Can ovarian aging be delayed by pharmacological strategies? Aging (Albany NY) 11, 817–832, 2019.10.18632/aging.101784636695630674710 Search in Google Scholar

Zhao X, Ze Y, Gao G, Sang X, Li B, Gui S, Sheng L, Sun Q, Cheng J, Cheng Z, Hu R, Wang L, Hong F. Nanosized TiO2-induced reproductive system dysfunction and its mechanism in female mice. PLoS One 8, e59378, 2013.10.1371/journal.pone.0059378361500823565150 Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo