Physiological and histological effects of (zinc and iron) oxide nanoparticles on some fertility parameters in female mice


  • Shaima R. Ibraheem Biotechnology department, Collage of Science, Baghdad University.
  • Muntaha R. Ibrahim Biomedical department, Alkawarizmi Collage of engineering, Baghdad University.



Nanoparticles, fertility, hormones, mice


Nowadays nanoparticles have widespread application in various industries
because of their special and unique features, there are many studies in side
effects of nanomaterial. This study done by 40 white female mice with
every other day intraperitoneally injection of low and high doses of both of
ZnO kg of body weight) and FeO
nanoparticles (5 and 40 mg/kg). After a 15 days period, the mice were
sacrificed and blood samples were collected for hormone analysis, and
tissue samples for morphometric studies.
Statistical Analysis shows significant differences in LH, Estrogen,
Progesterone hormone levels between groups, while there are insignificant
differences in Follicle stimulating hormone (FSH) level between the
groups compared with its level in the control group.
The results also show that the highest level of LH reach 7.2 mIU/ml in the
groups treated with low dose of zinc oxide, the highest level of FSH reach
4.58 mIU/ml in the groups treated with low dose of zinc oxide, the highest
level of Estrogen hormone reach 69.5 ng/ml in the groups treated with low
of dose zinc oxide and the highest level of Progesterone reach 1.9 ng/ml in
the groups treated with high dose iron oxide. We conclude from the results
that the low doses of ZnO has benefits in increasing fertility through high
level of reproductive hormones, while the high levels of nanoparticles
reduce fertility and there is a relation between FeO nanoparticles and
progesterone levels which may need more future studies.
Morphometric study of the ovary show increase in Follicular stages
number range in the group treated with Low dose ZnO in compare with its
range in the control groups. The lower range was belong to the group
treated with the high dose of FeO. No significant differences has been
found in the diameter mean of the different follicular phases between the
group treated with low dose of ZnO NPs in compared with the control
group. High dose of ZnO NPs cause significant increase in the diameter
mean of Primordial follicles in compared with the control group. Low and
high dose FeO NPs treated groups show significant reduction in the
diameter mean of the different follicular phases in compared with the
control group.


Noori, A., Momayez, M., Sadeghi, L., Shirani, K. and Babadi, V.Y. The effects of nano titanium dioxide (TiO2) in spermatogenesis in wistar rat. European J. of Exper. Bio., 3:145-149, 2013.

Ravishankar, R. V. and Jamuna B. A. Nanoparticles and their potential application as antimicrobials Science against microbial pathogens: communicating current research and technological advances. A. Méndez-Vilas (Ed.): 197-209, 2011.

Finney, L.A. and O'Halloran, T.V. Transition metal speciation in the cell: insights from the chemistry of metal ion receptors. Science, 9; 300:931-936, 2003.

Sharma,V., Shukla, R.K., Saxena, N., Parmar, D., Das, M. and Dhawan, A. DNA damaging potential of zinc oxide nanoparticles in human epidermal cells, Toxicol. Let., 185, 211-218, 2009.

Yousefi Babadi, L., Najafi, A., Najafi, H., Gholami, M., BeigiZarji,J., Golzadeh, E., Amraie,A. and Shirband, Evaluation of iron oxide nanoparticles effects on tissue and enzymes of liver in rats J. Pharma. Biomed. Sci.,, 23, 1-4, 2012.

Huang, Z., Zheng, X., Yan, D., Yin, G., Liao, X., Kang, Y., Yao, Y. and Huang D. Toxicological effect of ZnO nanoparticles based on bacteria, Hao. BLangmuir, 24, 4140-4144, 2008.

Brayner, R., Ferrari-Iliou R., Brivois N., Djediat S., Benedetti M.F. and Fievet F. Toxicological impact studies based on Escherichia coli bacteria in ultrafine ZnO nanoparticles colloidal medium. Nano. Lett.;6: 866–870, 2006.

Zhang L.L., Jiang Y.H., Ding Y.L., Povey M. and York D. Investigation into the antibacterial behavior of suspensions of ZnO nanoparticles (ZnO nanofluids). J.Nanopart. Res.; 9:479–489, 2007.

Nazem, H. and Arefian, Z. Effect of ZnO NPs on tumor marker hormones in male rats. Biomed. Res.; 26 (1): 82-88, 2015.

Sun, C., Lee, J.S. and Zhang, M. Magnetic nanoparticles in MRimaging and drug delivery, Adv. Drug, Deliv. Rev., 60, 1252-1265, 2008.

Park, E.J., Kim, H., Kim, Y., Yi, J., Choi, K. Inflammatory responses may be induced by a single intratracheal instillation of iron nanoparticles in mice.,Toxicol., 275, 65- 71, 2010.

Mirkovic, B., Lah-Turnsek, T. and Kos,J. Nanotechnology in the treatment of cancer, Zdrav.Vestn, 79, 146–155, 2010.

Wahajuddin, A. and Arora, S. Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers, Int. J. Nanomedicine, 7, 3445–3471, 2012.

Smijs,T.G, and Pavel,S Titanium dioxide and zinc oxide nanoparticles in sunscreens: focus on their safety and effectiveness. Nanotechnology, Science and Applications 2011:4 95–112, 2011.

Vahid, Y.B., Esmaiil,A., Hojatollah, S., Leila, S., Najafi Leila, N. and Fazilati, Mohammad, F. Evaluation of Iron Oxide nanoparticles effects on tissue and Enzymes of Thyroid in Rats. Intern. Res. J. of Biolog. Sci. ; 2: 67-69, 2013.

Reza, E. H., Mohammad, F., Leila, S. Vahid Y.B., Somayeh, B. and Esmail, A. Investigation the Zinc Oxide Nanoparticle’s Effect on Sex Hormones and Cholesterol in Rat. Intern. Res. J. of Biolog. Sci. 2: 54-58, 2013.

Bancrof, S, and Stevens, A. Enzyme histochemistry. In: Theory and practice of histological techniques Bancroft and steven, A. (eds), 2nd edition. Churchill living stone, London. PP: 3450. 1982.

Junqueira, L.C., Carneiro, J. and Kelley, R.O. Basic histology. Seventh ed. Connecticut, USA: Appleton & Lange, 1992.

SAS. 2010. Statistical Analysis System, User's Guide. Statistical. Version 9.1th ed. SAS. Inst. Inc.

Esmaeillou, M., Moharamnejad, M., Hsankhani, R., Tehrani, A.A. and Maadi, H. Toxicity of ZnO Nanoparticles in Healthy Adult Mice, Environ. Toxicol.Phar, 35: 67-71, 2013.

Espanani, H. R., Shirani, K. Sadeghi, L., YousefiBabadi, V. and Amraeai, E. Investigation of the Zinc Oxide Nanoparticles Effect on Testosterone, Cholesterol and Cortisol in Rats Res. J. Recent Sci. 3: 14-19, 2014.

Puran, B., Kazem, P., Seyed M., Seyed, D. and Alireza, S. Effect of nano-zinc oxide on doxorubicin- induced oxidative stress and sperm disorders in adult male Wistar rats. Iran J Reprod Med. 11: 355-364, 2013.

Zanetti, S.R., Maldonado, E.N. and Aveldaño, M.I. Doxorubicin Affects Testicular Lipids with Long-Chain (C18-C22) and Very Long-Chain (C24-C32) Polyunsaturated Fatty Acids. Cancer Res., 67: 6973-6980, 2007.

Andrieu, S. Is there a role for organic trace element supplements in transition cow health? Vet. J. 176:77-83, 2008.

Guo, D., Bia, H., Wang D. and Wu Q. Zinc Oxide Nanoparticles Decrease the Expression and Activity of Plasma Membrane Calcium ATPase, Disrupt The Intracellular Calcium homeostasis in Rat Retinal Ganglion Cells, Int. J. Biochem. Cell B, 45: 1849– 1859, 2013.

Han, D., Tian, Y., Zhang, T., Ren, G. and Yang, Z. Nano-Zno Damages Spatial Cognition Capability Via Over-Enhanced Long -Term Potentiation in Hippocampus of Wistar Rats, Int. J. Nanomedicine, (6):1453–1461, 2011.

Monteiro-Riviere, N.A., Wiench. K., Landsiedel. R., Schulte. S., Inman. A.O. and Riviere, J.E. Safety Evaluation of Sunscreen Formulations Containing Titanium Dioxide and Zno Nanoparticles in UVB Sunburned Skin: An In Vitro and In Vivo Study, Toxicol. Sci, 123: 264–280, 2011.

Landsiedel, R., Ma-Hock, L., Van Ravenzwaay, B, et al.., Gene toxicity Studies on Titanium Dioxide and Zno Nanomaterials Used for UV-Protection in Cosmetic, Nanotoxicology, 4, 364–381, 2010.

Wang, R.L., Liang, J.G., Lu, L., Zhang, L.Y., Li, S.F.and Luo, X.G. Effect of zinc source on performance, zinc status, immune response, and rumen fermentation of lactating cows. Biol.Trace Elem. Res. 152: 16-24, 2013.

Machadoa, V.S., Bicalhoa, M., Pereiraa, R.V., Caixetaa, L.S., Knauera, W.A., Oikonomoua, G., Gilbertb, R.O. and Bicalho R.C. Effect of an injecTable trace mineral supplement containing selenium, copper, zinc, and manganese on the health and production of lactating Holstein cows. Vet. J. 197: 451-456, 2013.

Sales, J.N., Pereira, R.V., Bicalho, R.C. and Baruselli, P.S. Effect of injecTable copper, selenium, zinc and manganese on the pregnancy rate of crossbred heifers (Bos indicus × Bos taurus) synchronized for timed embryo transfer. Livestock Science. 142: 59–62, 2011.

Gottsch, M.L., Murdoch, W.J. and Van Kirk, E.A. Tumour necrosis factor alpha upregulates matrix metalloproteinase-2 activity in preovulatory ovine follicles metamorphic and endocrine implications. Reprod. Fertil. Develop. 12: 75-80, 2000.

Aughey, E; Grant, L; Furman, B.L.; and Dryden, W. F. The effects of oral zinc supplementation in the mouse. J Comp Pathol 87:1-14, 1977.

Straube, E.F, Schuster, N.H. and Sinclair, J.A. Zinc toxicity in the ferret. J Comp Pathol 90:355-361, 1980.

Bombin,S.; LeFebvre,M; r Sherwood,J.; Xu,Y.; Yuping Bao,Y.; and Ramonell, K.M. Developmental and Reproductive Effects of Iron Oxide Nanoparticles in Arabidopsis thaliana. Int. J. Mol. Sci., 16, 24174-24193, 2015.

Soenen, S.J., Himmelreich, U., Nuytten, N. and De Cuyper, M. Cytotoxic Effects of Iron Oxide Nanoparticles and Implications for Safety in Cell Labelling. Biomaterials, 32, 195-205, 2011.

Ahamed M.; Alhadlaq, H.A., Alam, J., Khan, M.A., Ali, D. and Alarafi, S. Iron oxide nanoparticle-induced oxidative stress and genotoxicity in human skin epithelial and lung epithelial cell lines. Curr Pharm Des.;19 (37):6681-6690, 2013.

Weissleder, R.; Stark, D.D.; Engelstad, B.L.; Bacon, B.R.; Compton, C.C.; White, D.L.; Jacobs, P. and Lewis, J. Superparamagnetic iron oxide: Pharmacokinetics and toxicity. Am.J. Roentgenol. 152, 167–173, 1989.

Hussain, M.K.; Mohammed, H.J.; Al- Ghazali, B.S. and Abdul Hasan, M.T.. Oxidative Stress in Primary Infertility of Women. Glob. J. of Med. Res. 1(3),:1-8, 2013.

Gao, G., Ze, Y., Li, B., Zhao, X., Zhang, T., Sheng, L., Hu, R., Gui, S., Sang, X., Sun, Q., et al.. 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.

Iavicoli, I.; Fontana, L.; Leso, V. and Bergamaschi. A. The Effects of Nanomaterials as Endocrine Disruptors Int. J. Mol. Sci., 14 : 16732-16801, 2013.

Kolesarova, A., Capcarova, M., Medvedova, M., Sirotkin, A.V. and Kovacik, K. In Vitro Assessment of Iron Effect on Porcine Ovarian Granulosa Cells: Secretory Activity, Markers of Proliferation and Apoptosis. Physiol. Res. 60: 503-510, 2011.

Kojadinovic, J., Potier, M., Le, Corre, M., Cosson, R. P., and Bustamante, P. Bioaccumulation of Trace Elements in Pelagic Fish from the Western Indian Ocean. Environmental Pollution, 146,: 548-566, 2007.

Bires, J., Dianovsky, J., Bartko, P., Juhasova, Z. Effects on enzymes and the genetic apparatus of sheep after administration of samples from industrial emissions.Bio Metals, 8:53–58, 1995.

Ynsa, M.D., Ager, F.J., Millan, J.C.;Gomez-zubelbia, M.A. and Pinheiro, T. Effect of hormone replacement therapy on the elemental contents of uterine tissue. Biol Trace Elem Res. 101: 37-46, 2004.

Reilly, C. The Nutritional Trace Metals. Blackwell Publishing, Ltd, Oxford, PP: 1-238, 2004.

Defrere, S., Lousse J.C., Gonzaleez -Ramos, R., Colette, S., Donnez, J., VanL-angendonckt, A. Potential involvement of iron in the pathogenesis of peritoneal endometriosis. Mol Hum Reprod 14: 377-385, 2008.

Durlej,M,, Duda, M., Knapczyk, K.,Slomczynska,M. Effects of transferrin on aromatase activity in porcine granulosa cells in vitro. Folia Histochem. Cytobiol. 46: 423-428, 2008.

Kolesarova, A., Roychoudhury, S., Slivkova, L. J., Sirotkin, A., Capcarova, M., Massanyi, P. In vitro study on the effect of lead and mercury on porcine ovarian granulosa cells. J. Environ Sci. Health A Tox Hazard Subst Environ Eng., 45:320-331, 2010.

K Kolesarova, A., Capcarova, M., Sirotkin, A., Medvedova, M., Kovacik, J. Cobalt-induced changes in the IGF-I and progesteron release, expression of proliferation- and apoptosis-related peptides in porcine ovarian granulosa cells in vitro. J. Environ. Sci. Health A Tox Hazard Subst Environ Eng 45: 810-817, 2010b.

Risom, L., Moller, P., Loft, S. Oxidative stress-induced DNA damage by particulate air pollution Mutat. Res., 592:119-137, 2005.




How to Cite

S. R. Ibraheem and M. R. Ibrahim, “Physiological and histological effects of (zinc and iron) oxide nanoparticles on some fertility parameters in female mice”, MJS, vol. 27, no. 5, pp. 1–10, Jul. 2017.



Biological Science