Ultrastructure of oviducts: numerous microvilli and rare cilia were evident on the surface of the columnar secretory cells (Fig. 20).
IHC detection of leptin: positive immune reaction for leptin was detected in the cytoplasm of the epithelial cells and in the endothelium lining blood vessels (Fig. 21).
Compared with negative control rats in group I, rats receiving MSG in group II revealed a significant (P<0.05) increase in body weight, total serum cholesterol level, and height of epithelial cells. However, there was an insignificant increase (P>0.05) in the number of epithelial cells. Rats receiving CoQ10 together with MSG in group IV revealed an insignificant increase in the body weight, total serum cholesterol level, height of epithelial cells, and number of epithelial cells (P>0.05) (Table 1).
The ampullary region of oviduct is a strategic site in which fertilization and early embryonic development occur. Its fluid composition is involved in the optimization of the microenvironment for fertilization and early cleavage stage in embryonic development .
In this study, the histological structures of the ampulla of control group at diestrous phase showed predominant secretory cells and few ciliated cells. Different studies reported that, during the diestrous phase, the secretory cells are the dominating cell type and the ciliated cells are reduced in number [3,20,21]. The secretory cells have apical microvilli and many secretory vesicles variable in size and shape . The secretory cells secrete glycoproteins, which reduce the incidence of polyspermy and increase postcleavage development to blastocyst .
Increased use of chemicals due to advanced technology can seriously harm female fertility. A great danger is hidden in the increased use of different food additives such as MSG . It is generally believed that more than 70 million couples suffer from infertility worldwide .
In this study, group II receiving MSG showed a significant increase in the total serum cholesterol level and epithelial cell height. However, the increase in the epithelial cell number was not significant. Moreover, different structural changes in the oviduct in the form of overcrowded epithelial cells and thickening in the corium and musculosa associated with mitotic figures in fibroblasts of the corium were encountered. Similar findings were reported in other studies [24,25]. The exact mechanism of how MSG induced cellular overcrowding is not clear. However, some investigators suggested that increase in the levels of total protein, cholesterol, and estrogen by MSG may lead to an increase in cell proliferation . Furthermore, other studies reported that hypercholesterolemia can promote the proliferation of fibroblasts .
In oviducts of rats that received MSG, many inflammatory cells were seen in the lumen and between epithelial cells. This was reported before by another study . MSG cause oxidative stress, leading to an increase in the inflammatory markers . The accumulation of inflammatory cells in the female genital organs may lead to infertility .
Dilated Golgi apparatus and rough endoplasmic reticulum were detected in group II. It was reported that glutamate metabolism occurs through transport from the endoplasmic reticulum to the Golgi apparatus ; therefore, MSG can alternate protein synthesis .
Some epithelial cells showed many vacuoles and lysosomes in their cytoplasm as a result of MSG intake. In agreement with this finding, a previous study reported cell death due to degeneration induced by MSG in the form of apoptosis and necrosis . MSG is a cytotoxic substance that may enhance autophagy of the cells resulting in apoptosis .
Disrupted mitochondria with failure of their division and fusion were detected in group II. The mitochondrial division and fusion play a major role in controlling the morphology of the organelle and maintain the function of healthy cells. Loss of fusion and division have been linked to loss of mitochondrial membrane potential in addition to reduced respiratory activity and apoptosis . It was mentioned that glutamate induces Ca2+ influx and disruption of the inner transmembrane potential of the mitochondria, resulting in opening of the mitochondrial permeability transition pore . This will lead to release of essential factors of apoptosis, which have the ability to activate caspases into the cytosol resulting in apoptosis .
Leptin is a hormone originally identified in adipocytes. It is involved in the regulation of fat deposition and energy expenditure and in other functions, such as reproduction .
In this study, control group showed a positive IHC reaction for leptin in the cytoplasm of the ampullary epithelium of the oviduct and in the endothelium lining blood vessels. Different studies proved a strong positive reaction for leptin in the cytoplasm of secretory cells of the ampulla than in other parts of the oviduct  and in endothelial cells [5,12].
Overweight animals showed negative immune reaction for leptin in this study. Studies have indicated for decades that MSG intake causes overweight and obesity as a result of hypothalamic and arcuate nuclei damage, resulting in the lack of control between absorption and energy expenditure [34,35]. Many studies reported a link between the decrease in leptin production and obesity as leptin modulates food intake and energy homeostasis [36,37]. In contrast, some investigators postulated that mice with diet-induced obesity such as MSG exhibit circulating hyperleptinemia. However, there is a resistance to the metabolic actions of leptin and absence of its expression in the cells [38,39]. This negative immune reaction for leptin may cause infertility. It was reported that a negative IHC reaction for leptin in an ovulatory cycle may contribute to subfertility .
CoQ10 is an endogenously synthesized compound that acts as an electron carrier in the mitochondrial respiratory chain. It is involved in the reactive oxygen species removal and prevention of oxidative stress-induced apoptosis. In addition, it has potential benefits to decrease inflammation [41,42] and to enhance neuroprotection . It was reported that CoQ10 improves fertility in aged female mice through an increase in the quantity and quality of ovulated eggs .
In this study, CoQ10 was given alone in group III rats in a dose that did not alter the structure, ultrastructure, or the IHC reaction. When a similar dose of CoQ10 was given with MSG, the structural and ultrastructural degenerative changes induced by MSG were prevented and the positive immune reaction for leptin in the epithelium of the oviduct was preserved. Different studies reported that CoQ10 can inhibit fibrosis  and dramatically reduced apoptotic cell death [46,47]. Moreover, there was no significant increase in the body weight and total serum cholesterol in this group compared with the control group. It was proved that CoQ10 can strongly inhibit adipogenesis  and can decrease the body weight and serum cholesterol , reflecting a partial protective role of CoQ10.
Administration of MSG resulted in changes in the histology and in the IHC expression of leptin in the ampulla of the oviducts in adult female albino rats during the diestrous phase. The administration of CoQ10 with MSG partially prevented the occurrence of such changes and regulated leptin expression, suggesting a possibility to use CoQ10 in concomitant with MSG to decrease its toxic effect.
The safety use of MSG should be reconsidered with a potential to withdraw MSG from the food chain. Furthermore, the possible role of CoQ10 in ameliorating the toxic effect of MSG on the oviducts and on other female genital organs should be examined to raise a possibility to use CoQ10 in cases of unexplained infertility, which may be due to nutritive habits.
1. Archanco M, Gómez Ambrosi J, Tena Sempere M, Frühbeck G, Burrell MA. Expression of leptin and adiponectin in the rat oviduct. J Histochem Cytochem. 2007;55:1027–1037
2. Bojanić V, Bojanić Z, Najman S, Savić T, Jakovljević V, Najman S, Jančić S. Diltiazem prevention of toxic effects of monosodium glutamate on ovaries in rats. Gen Physiol Biophys. 2009;28:149–154
3. Hasanain NA, Saqqara ZA, El Hadidi AR. Scanning and transmission electron micoscopic study of the oviductal epithelium of female albino rat during follicular and luteal phases of the estrous cycle. Egypt J Anat. 2001;24:59–79
4. Kress A, Morson G. Changes in the oviductal epithelium during the estrous cycle in the marsupial Monodelphis domestica
. J Anat. 2007;211:503–517
5. Loffler S, Aust G, Kohler U, Spanel Borowski K. Evidence of leptin expression in normal and polycystic human ovaries. Mol Hum Reprod. 2001;7:1143–1149
6. Wollenhaupt K, Tomek W, Brussow KP, Tiemann U, Viergutz T, Schneider F, Nurnberg G. Effects of ovarian steroids and epidermal growth factor (EGF) on expression and bioactivation of specific regulators of transcription and translation in oviductal tissue in pigs. Reproduction. 2002;123:87–96
7. Moore KL Congenital malformations due to environmental factors; developing humans. 20032nd ed Philadelphia W.B. Saunders Co. Ltd
8. Farombi EO, Onyema OO. Monosodium glutamate-induced oxidative damage and genotoxicity in the rat: modulatory role of vitamin C, vitamin E and quercetin. Hum Exp Toxicol. 2006;25:251–259
9. Bhagavan HN, Chopra RK. Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics. Free Radic Res. 2006;40:445–453
10. Pravst I, Žmitek K, Žmitek J. Coenzyme Q10 contents in foods and fortification strategies. Crit Rev Food Sci Nutr. 2010;50:269–280
11. Golbidi S, Laher I. Antioxidant therapy in human endocrine disorders. Med Sci Monit. 2010;16:RA9–RA24
12. Archanco M, Muruzabal FJ, Llopiz D, Garayoa M, Gomez Ambrosi J, Fruhbeck G, Burrell MA. Leptin expression in the rat ovary depends on estrous cycle. J Histochem Cytochem. 2003;51:1269–1277
13. Celik S, Akarcay H, Yilmaz O, Ozkaya A. Effects of intraperitoneally administered ubiquinone on the level of total lipid and fatty acids in rat liver. Cell Biochem Funct. 2006;24:561–564
14. Obochi GO, Malu SP, Obi Abang M, Alozie Y, Iyam MA. Effect of garlic extracts on monosodium glutamate (MSG) induced fibroid in Wistar rats. Pak J Nutr. 2009;8:970–976
15. Rowland MA, Nagley P, Linnane AW, Rosenfeldt FL. Coenzyme Q10 treatment improves the tolerance of the senescent myocardium to pacing stress in the rat. Cardiovasc Res. 1998;40:165–173
16. Bancroft JD, Gamble M Theory and practice of histological techniques. 20086th ed Edinburgh Churchill Livingstone
17. Steinhauer N, Boos A, Gunzel Apel AR. Morphological changes and proliferative activity in the oviductal epithelium during hormonally defined stages of the oestrous cycle in the bitch. Reprod Domest Anim. 2004;39:110–119
18. Ramos Vara JA, Kiupel M, Baszier T, Bliven L, Brodersen B, Chelack B, et al. Suggested guidelines for immunohistochemical techniques in veterinary diagnostic laboratories. J Vet Diagn Invest. 2008;20:393–413
19. Schoonjans F, Zalata A, Depuydt CE, Comhaire FH. MedCalc: a new computer program for medical statistics. Comput Methods Programs Biomed. 1995;48:257–262
20. Desantis S, Ventriglia G, Zubani D, Corriero A, Deflorio M, Acone F, et al. Differential lectin binding patterns in the oviductal ampulla of the horse during oestrus. Eur J Histochem. 2005;49:139–149
21. Zerani M, Boiti C, Dall'Aglio C, Pascucci L, Maranesi M, Brecchia G, et al. Leptin receptor expression and in vitro leptin actions on prostaglandin release and nitric oxide synthase activity in the rabbit oviduct. J Endocrinol. 2005;185:319–325
22. Kouba AJ, Abeydeera LR, Alvarez IM, Day BN, Buhi WC. Effects of the porcine oviduct-specific glycoprotein on fertilization, polyspermy and embryonic development. Biol Reprod. 2000;63:242–250
23. Boivin J, Bunting L, Collins JA, Nygren KG. International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Hum Reprod. 2007;22:1506–1512
24. Collison KS, Maqbool Z, Saleh SM, Inglis A, Makhoul NJ, Bakheet R, et al. Effect of dietary monosodium glutamate on trans fat-induced nonalcoholic fatty liver disease. J Lipid Res. 2009;50:1521–1537
25. Eweka AO, Eweka A, Om'Iniabohs FAE. Histological studies of the effects of monosodium glutamate of the fallopian tubes of adult female Wistar rats. North Am J Med Sci. 2010;2:146–149
26. Chen BY, Wei JG, Wang YC, Yu J, Qian JX, Chen YM, Xu J. Effects of cholesterol on proliferation and functional protein expression in rabbit bile duct fibroblasts. World J Gastroenterol. 2004;10:889–893
27. Onyema OO, Farombi EO, Emerole GO, Ukoha AI, Onyeze GO. Effect of vitamin E on monosodium glutamate induced hepatotoxicity and oxidative stress in rats. Indian J Biochem Biophys. 2006;43:20–24
28. Haggerty CL, Totten PA, Astete SG, Lee S, Hoferka SL, Kelsey SF, Ness RB. Failure of cefoxitin and doxycycline to eradicate endometrial mycoplasma genitalium and the consequence for clinical cure of pelvic inflammatory disease. Sex Transm Infect. 2008;84:338–342
29. Yang G, Xiong W, Kojic L, Cynader MS. Subunit-selective palmitoylation regulates the intracellular trafficking of AMPA receptor. Eur J Neurosci. 2009;30:35–46
30. Pavlović V, Cekić S, Kocić G, Sokolović D, Živković V. Effect of monosodium glutamate on apoptosis and Bcl-2/Bax protein level in rat thymocyte culture. Physiol Res. 2007;56:619–626
31. Suen DF, Norris KL, Youle RJ. Mitochondrial dynamics and apoptosis. Genes Dev. 2008;22:1577–1590
32. Kanki R, Nakamizo T, Yamashita H, Kihara T, Sawada H, Uemura K, et al. Effects of mitochondrial dysfunction on glutamate receptor-mediated neurotoxicity in cultured rat spinal motor neurons. Brain Res. 2004;1015:73–81
33. Desagher S, Martinou JC. Mitochondria as the central control point of apoptosis. Trends Cell Biol. 2000;10:369–377
34. Von Diemen V, Trindade EN, Trindade MR. Experimental model to induce obesity in rats. Acta Cir Bras. 2006;21:425–429
35. Hermanussen M, Tresguerres JA. Does high glutamate intake cause obesity? J Pediatr Endocrinol Metab. 2003;16:965–968
36. Ceccarini G, Flavell RR, Butelman ER, Synan M, Willnow TE, Bar Dagan M, et al. PET imaging of leptin biodistribution and metabolism in rodents and primates. Cell Metab. 2009;10:148–159
37. Da Paz Filho GJ, Volaco A, Suplicy HL, Radominski RB, Boguszewski CL. Decrease in leptin production by the adipose tissue in obesity associated with severe metabolic syndrome. Arq Bras Endocrinol Metab. 2009;3:1088–1095
38. El Haschimi K, Pierroz DD, Hileman SM, Bjorbaek C, Flier JS. Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J Clin Invest. 2000;105:1827–1832
39. Giovambattista A, Suescun MO, Nessralla CC, Franca LR, Spinedi E, Calandra RS. Modulatory effects of leptin on leydig cell function of normal and hyperleptinemic rats. Neuroendocrinology. 2003;78:270–279
40. Alfer J, Muller Schottle F, Classen Linke I, Von Rango U, Happel L, Beier Hellwig K, et al. The endometrium as a novel target for leptin: differences in fertility and subfertility. Mol Hum Reprod. 2000;6:595–601
41. Naderi J, Somayajulu Nitu M, Mukerji A, Sharda P, Sikorska M, Borowy Borowski H, et al. Water-soluble formulation of coenzyme Q10 inhibits Bax-induced destabilization of mitochondria in mammalian cells. Apoptosis. 2006;11:1359–1369
42. Kunitomo M, Yamaguchi Y, Kagota S, Otsubo K. Beneficial effect of coenzyme Q10 on increased oxidative and nitrative stress and inflammation and individual metabolic components developing in a rat model of metabolic syndrome. J Pharmacol Sci. 2008;107:128–137
43. Kooncumchoo P, Sharma S, Porter J, Govitrapong P, Ebadi M. Coenzyme Q(10) provides neuroprotection in iron-induced apoptosis in dopaminergic neurons. J Mol Neurosci. 2006;28:125–141
44. Burstein E, Perumalsamy A, Bentov Y, Esfandiari N, Jurisicova A, Casper RF. Coenzyme Q10 supplementation improves ovarian response and mitochondrial function in aged mice. Fertil Steril. 2009;92(Suppl 3):S31
45. Choi HK, Pokharel YR, Lim SC, Han HK, Ryu CS, Kim SK, et al. Inhibition of liver fibrosis by solubilized coenzyme Q10: role of Nrf2 activation in inhibiting transforming growth factor-β1 expression. Toxicol Appl Pharmacol. 2009;240:377–384
46. Papucci L, Schiavone N, Witort E, Donnini M, Lapucci A, Tempestini A, et al. Coenzyme q10 prevents apoptosis by inhibiting mitochondrial depolarization independently of its free radical scavenging property. J Biol Chem. 2003;278:28220–28228
47. Kernt M, Hirneiss C, Neubauer AS, Ulbig MW, Kampik A. Coenzyme Q10 prevents human lens epithelial cells from light-induced apoptotic cell death by reducing oxidative stress and stabilizing BAX/Bcl-2 ratio. Acta Ophthalmol. 2010;88:e78–e86
48. Bour S, Carmona MC, Galinier A, Caspar Bauguil S, Van Gaal L, Staels B, et al. Coenzyme Q as an antiadipogenic factor. Antioxid Redox Signal. 2011;14:403–413
49. Modi KP, Vishwakarma SL, Goyal RK, Bhatt PA. Effects of coenzyme Q10 on lipid levels and antioxidant defenses in rats with fructose induced hyperlipidemia and hyperinsulinaemia. Internet J Pharmacol. 2007;5:1531