Gold Nanoparticles Enter Rat Ovarian Granulosa Cells and Subcellular Organelles, and Alter <i>In-Vitro</i> Estrogen Accumulation

Abstract

Abstract. Nanoparticle technology refers to research and technology developed at the atomic or molecular level for materials of approximately 1-100 nm in length. Through accidental or involuntary exposure, nanoparticles are potentially toxic to the body, including reproductive organs. Ovarian granulosa cells play a major role in maintaining ovarian function, health, and female fertility. Since these cells are involved in steroidogenesis, we wished to evaluate whether nanoparticles affected them after traversing their membranes. Cells were co-incubated with 10 nm gold particles for up to 24 h. Transmission electron micrographs were taken of GC treated with 10 nm gold particles in order to compare and contrast ultrastructural locations of nanoparticles with treatment. From micrograph comparisons of treated vs. untreated GC at various culture times, it appeared that some intracellular organelles involved in steroidogenesis were infiltrated and/or altered due to the presence of the nanogold particles. Medium samples were taken in order to determine estradiol-17beta (E2) accumulation/secretion by untreated vs. treated cells. GC incubated with 10 nm nanogold particles for 1, 3, or 5 h were found to accumulate significantly increased amounts of estrogen compared with untreated cells. Conversely, at 24 h there was a significant attenuation with respect to controls. The data presented here provide insight into the toxicologic effects gold nanoparticles elicit on ovarian granulosa cells. Key words: Estrogen, Granulosa cells, Nanoparticles, Steroidogenesis, Transmission electron microscopy (J. Reprod. Dev. 55: [685][686][687][688][689][690] 2009) anomaterial technology has become a dynamic and exciting topic in biology over the past ten years. A decade ago nanoparticles were studied because of their size-dependent physical and chemical properties. Now they have entered a commercial exploration period [1]. Nanomaterials come in a variety of shapes, sizes, and elemental forms and are currently produced in a wide variety of types for a plethora of applications; fullerenes, carbon nanotubes, metal and metal oxide particles, polymer nanoparticles, and quantum dots are among the most common [2][3][4][5]. At these "nano" sizes, the toxicologic effects of common elements such as carbon, silicon, gold and titanium have not been studied very closely.In order for nanoparticles to exert toxicologic effects they must first cross the cell membrane. It is important to study the process by which nanoparticles gain access to the cell because of their possible toxicologic and health implications [6][7][8][9][10][11][12][13][14][15][16][17][18]; however, to date there have been few studies on this area of concern. The increased use of nanoparticles in research, medicine, and the manufacture of consumer products, therefore, creates an urgent need to test the toxic potential of these materials. Considering that nanoparticles can travel to distant locations in the body and move across cell membranes of many types of cells, it is certainly co...

Copper nanoparticle-induced ovarian injury, follicular atresia, apoptosis, and gene expression alterations in female rats

“…25 In addition, gold NPs can enter Chinese hamster ovary cells through the endocytic pathway, 26 infiltrate rat ovarian granulosa cells and subcellular organelles, and alter in vitro estrogen accumulation. 27 Moreover, mitogen-activated protein kinase cellular signal transduction pathways in mammalian cells can be activated by silicon carbide nanowires. 28 Furthermore, evidence has shown that chronic exposure of Enchytraeus albidus worms to Cu NPs results in lower reproductive output compared to exposure to CuCl 2 salt.…”

Ovarian dysfunction and gene-expressed characteristics of female mice caused by long-term exposure to titanium dioxide nanoparticles

“…Recently, the toxicologic characteristics of some nanomaterials in ovarian cells in vitro have been reported. For instance, gold nanoparticles were shown to enter rat ovarian granulosa cells and subcellular organelles and alter estrogen accumulation in vitro [23], and were able to traverse the cell membrane and enter Chinese hamster ovary cells by the endocytic pathway [24]. In addition, calcium phosphate nanoparticles entered granulosa cells, and were distributed in the membranous compartments, including lysosome, mitochondria and intracellular vesicles, affected hormone production, and caused apoptosis in human granulosa cells [25].…”

Subcellular localization of gold nanoparticles in the estuarine bivalve Scrobicularia plana after exposure through the water

“…Most investigators studied specific nanoparticle interactions with single cellular system in which parameters can be controlled, even though this type of model is artificial. Up to date, no consensus exist in regard with the subcellular location of AuNPs (reviewed in Khlebtsov and Dykman [17]): freely dispersed in cytoplasm [18][19][20] clustered in vesicles [7,11,12,18,21,22]. Some studies showed a high fraction of radioactive AuNPs linked to DNA [23], an aggregation of small AuNPs (2 nm) within the nuclei which were damaged [24], a nuclear fragmentation [25,26].…”