Browse > Article
http://dx.doi.org/10.5653/cerm.2020.00388

Comparison of male reproductive parameters in mice with type 1 and type 2 diabetes  

Sampannang, Apichakan (Department of Anatomy, Faculty of Medicine, Khon Kaen University)
Arun, Supatcharee (Department of Anatomy, Faculty of Medicine, Khon Kaen University)
Burawat, Jaturon (Department of Anatomy, Faculty of Medicine, Khon Kaen University)
Sukhorum, Wannisa (Department of Anatomy, School of Medicine, Mae Fah Luang University)
Iamsaard, Sitthichai (Department of Anatomy, Faculty of Medicine, Khon Kaen University)
Publication Information
Clinical and Experimental Reproductive Medicine / v.47, no.1, 2020 , pp. 20-33 More about this Journal
Abstract
Objective: The differences between type 1 and type 2 diabetes mellitus (T1DM and T2DM) in terms of their adverse effects on male reproductive parameters have never been elucidated. This study aimed to distinguish between the effects of the DM types in mice treated with multiple low doses of streptozotocin (STZ) to mimic human T1DM and coadministered a high-fat diet (HFD) to mimic human T2DM. Methods: The T1DM mice were intraperitoneally injected with STZ (40 mg/kg body weight) for 5 days. The T2DM mice received an HFD for 14 days prior to STZ injection (85 mg/kg body weight), followed by continuous feeding of an HFD. Male reproductive parameters were evaluated. Results: The reproductive organs of the DM mice weighed significantly less than those of controls, and the seminal vesicles plus prostates of the T1DM mice weighed less than those of the T2DM mice. Increased sperm abnormalities and incomplete DNA packaging were observed in the DM groups. Sperm concentration and the proportion of normal sperm were significantly lower in the T1DM group. The seminiferous histopathology of DM mice was classified into seven types. The penises of the DM mice were smaller than those of the controls; however, tunica albuginea thickness and the amount of penile collagen fibers were increased in these mice. Round germ cells were abundant in the epididymal lumens of the mice with DM. Conclusion: T1DM adversely affected reproductive parameters to a greater extent than T2DM.
Keywords
Mice; Sperm; Streptozotocin; Type 1 diabetes mellitus; Type 2 diabetes mellitus;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997;20:1183-97.   DOI
2 American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2013;36 Suppl 1:S67-74.   DOI
3 American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2009;32 Suppl 1:S62-7.   DOI
4 Frier BM, Fisher M. Diabetes mellitus. In: Colledge NR, Walker BR, Ralston S, Davidson S, editors. Davidson's principles and practice of medicine. India: Elsevier; 2010. p. 735.
5 Ahangarpour A, Oroojan AA, Heidari H, Ghaedi E, Taherkhani R. Effects of hydro-alcoholic extract from Arctium lappa L. (Burdock) root on gonadotropins, testosterone, and sperm count and viability in male mice with nicotinamide/streptozotocin-induced type 2 diabetes. Malays J Med Sci 2015;22:25-32.
6 Ahangarpour A, Oroojan AA, Khorsandi L, Arzani G, Afshari G. Effects of betulinic acid on the male reproductive system of a streptozotocin-nicotinamide-induced diabetic mouse model. World J Mens Health 2016;34:209-16.   DOI
7 Alves MG, Martins AD, Moreira PI, Carvalho RA, Sousa M, Barros A, et al. Metabolic fingerprints in testicular biopsies from type 1 diabetic patients. Cell Tissue Res 2015;362:431-40.   DOI
8 Ding GL, Liu Y, Liu ME, Pan JX, Guo MX, Sheng JZ, et al. The effects of diabetes on male fertility and epigenetic regulation during spermatogenesis. Asian J Androl 2015;17:948-53.   DOI
9 Cai L, Chen S, Evans T, Deng DX, Mukherjee K, Chakrabarti S. Apoptotic germ-cell death and testicular damage in experimental diabetes: prevention by endothelin antagonism. Urol Res 2000;28:342-7.   DOI
10 Agbaje IM, Rogers DA, McVicar CM, McClure N, Atkinson AB, Mallidis C, et al. Insulin dependant diabetes mellitus: implications for male reproductive function. Hum Reprod 2007;22:1871-7.   DOI
11 Alves MG, Martins AD, Cavaco JE, Socorro S, Oliveira PF. Diabetes, insulin-mediated glucose metabolism and Sertoli/blood-testis barrier function. Tissue Barriers 2013;1:e23992.   DOI
12 Xu Y, Lei H, Guan R, Gao Z, Li H, Wang L, et al. Studies on the mechanism of testicular dysfunction in the early stage of a streptozotocin induced diabetic rat model. Biochem Biophys Res Commun 2014;450:87-92.   DOI
13 Zha W, Bai Y, Xu L, Liu Y, Yang Z, Gao H, et al. Curcumin attenuates testicular injury in rats with streptozotocin-induced diabetes. Biomed Res Int 2018;2018:7468019.   DOI
14 Yanagimachi R, Usui N. Calcium dependence of the acrosome reaction and activation of guinea pig spermatozoa. Exp Cell Res 1974;89:161-74.   DOI
15 Menkveld R, Holleboom CA, Rhemrev JP. Measurement and significance of sperm morphology. Asian J Androl 2011;13:59-68.   DOI
16 Venkatesh S, Gurdeep Singh MP, Prasad Gupta N, Kumar R, Deecaraman M, et al. Correlation of sperm morphology and oxidative stress in infertile men. Iran J Reprod Med 2009;7:29-34.
17 Carrell DT, Emery BR, Hammoud S. Altered protamine expression and diminished spermatogenesis: what is the link? Hum Reprod Update 2007;13:313-27.   DOI
18 Talebi AR, Vahidi S, Aflatoonian A, Ghasemi N, Ghasemzadeh J, Firoozabadi RD, et al. Cytochemical evaluation of sperm chromaand DNA integrity in couples with unexplained recurrent spontaneous abortions. Andrologia 2012;44 Suppl 1:462-70.   DOI
19 Ventura-Sobrevilla J, Boone-Villa VD, Aguilar CN, Roman-Ramos R, Vega-Avila E, Campos-Sepulveda E, et al. Effect of varying dose and administration of streptozotocin on blood sugar in male CD1 mice. Proc West Pharmacol Soc 2011;54:5-9.
20 Li X, Xu Z, Jiang Z, Sun L, Ji J, Miao J, et al. Hypoglycemic effect of catalpol on high-fat diet/streptozotocin-induced diabetic mice by increasing skeletal muscle mitochondrial biogenesis. Acta Biochim Biophys Sin (Shanghai) 2014;46:738-48.   DOI
21 Mali VR, Ning R, Chen J, Yang XP, Xu J, Palaniyandi SS. Impairment of aldehyde dehydrogenase-2 by 4-hydroxy-2-nonenal adduct formation and cardiomyocyte hypertrophy in mice fed a high-fat diet and injected with low-dose streptozotocin. Exp Biol Med (Maywood) 2014;239:610-8.   DOI
22 Sampannang A, Arun S, Sukhorum W, Burawat J, Nualkaew S, Maneenin C, et al. Antioxidant and hypoglycemic effects of Momordica cochinchinensis Spreng: (Gac) aril extract on reproductive damages in streptozotocin (STZ)-induced hyperglycemia mice. Int J Morphol 2017;35:667-75.   DOI
23 Sampannang A, Arun S, Burawat J, Sukhorum W, Iamsaard S. Testicular histopathology and phosphorylated protein changes in mice with diabetes induced by multiple-low doses of streptozotocin: an experimental study. Int J Reprod Biomed (Yazd) 2018;16:235-46.   DOI
24 Rossini AA, Williams RM, Appel MC, Like AA. Complete protection from low-dose streptozotocin-induced diabetes in mice. Nature 1978;276:182-4.   DOI
25 Chaudhry ZZ, Morris DL, Moss DR, Sims EK, Chiong Y, Kono T, et al. Streptozotocin is equally diabetogenic whether administered to fed or fasted mice. Lab Anim 2013;47:257-65.   DOI
26 Reed MJ, Meszaros K, Entes LJ, Claypool MD, Pinkett JG, Gadbois TM, et al. A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat. Metabolism 2000;49:1390-4.   DOI
27 Srinivasan K, Viswanad B, Asrat L, Kaul CL, Ramarao P. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacol Res 2005;52:313-20.   DOI
28 Ward MA. Intracytoplasmic sperm injection effects in infertile azh mutant mice. Biol Reprod 2005;73:193-200.   DOI
29 Zhang M, Lv XY, Li J, Xu ZG, Chen L. The characterization of highfat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Exp Diabetes Res 2008;2008:704045.
30 Bose R, Adiga SK, D'Souza F, Salian SR, Uppangala S, Kalthur G, et al. Germ cell abnormalities in streptozotocin induced diabetic mice do not correlate with blood glucose level. J Assist Reprod Genet 2012;29:1405-13.   DOI
31 Arun S, Burawat J, Sukhorum W, Sampannang A, Maneenin C, Iamsaard S. Chronic restraint stress induces sperm acrosome reaction and changes in testicular tyrosine phosphorylated proteins in rats. Int J Reprod Biomed (Yazd) 2016;14:443-52.   DOI
32 Sukhorum W, Iamsaard S. Changes in testicular function proteins and sperm acrosome status in rats treated with valproic acid. Reprod Fertil Dev 2017;29:1585-92.   DOI
33 Amaral S, Oliveira PJ, Ramalho-Santos J. Diabetes and the impairment of reproductive function: possible role of mitochondria and reactive oxygen species. Curr Diabetes Rev 2008;4:46-54.   DOI
34 Mangoli E, Talebi AR, Anvari M, Pourentezari M. Effects of experimentally-induced diabetes on sperm parameters and chromatin quality in mice. Iran J Reprod Med 2013;11:53-60.
35 Terquem T, Dadoune JP. Aniline blue staining of human spermatozoa chromatin: evaluation of nuclear maturation. In: Andre J, editor. The sperm cell. London: The Hague, Martinus Nijhoff; 1983. p. 249-52.
36 Soudamani S, Malini T, Balasubramanian K. Effects of streptozotocin-diabetes and insulin replacement on the epididymis of prepubertal rats: histological and histomorphometric studies. Endocr Res 2005;31:81-98.   DOI
37 Rahimi R, Nikfar S, Larijani B, Abdollahi M. A review on the role of antioxidants in the management of diabetes and its complications. Biomed Pharmacother 2005;59:365-73.   DOI
38 Navarro-Casado L, Juncos-Tobarra MA, Chafer-Rudilla M, de Onzono LI, Blazquez-Cabrera JA, Miralles-Garcia JM. Effect of experimental diabetes and STZ on male fertility capacity: study in rats. J Androl 2010;31:584-92.   DOI
39 Long L, Wang J, Lu X, Xu Y, Zheng S, Luo C, et al. Protective effects of scutellarin on type II diabetes mellitus-induced testicular damages related to reactive oxygen species/Bcl-2/Bax and reactive oxygen species/microcirculation/staving pathway in diabetic rat. J Diabetes Res 2015;2015:252530.   DOI
40 Ishii H, Jirousek MR, Koya D, Takagi C, Xia P, Clermont A, et al. Amelioration of vascular dysfunctions in diabetic rats by an oral PKC beta inhibitor. Science 1996;272:728-31.   DOI
41 Mohasseb M, Ebied S, Yehia MA, Hussein N. Testicular oxidative damage and role of combined antioxidant supplementation in experimental diabetic rats. J Physiol Biochem 2011;67:185-94.   DOI
42 Fernandes GS, Fernandez CD, Campos KE, Damasceno DC, Anselmo-Franci JA, Kempinas WD. Vitamin C partially attenuates male reproductive deficits in hyperglycemic rats. Reprod Biol Endocrinol 2011;9:100.   DOI
43 Khaneshi F, Nasrolahi O, Azizi S, Nejati V. Sesame effects on testicular damage in streptozotocin-induced diabetes rats. Avicenna J Phytomed 2013;3:347-55.
44 Donmez YB, Kizilay G, Topcu-Tarladacalisir Y. MAPK immunoreactivity in streptozotocin-induced diabetic rat testis. Acta Cir Bras 2014;29:644-50.   DOI
45 Jelodar G, Khaksar Z, Pourahmadi M. Endocrine profile and testicular histomorphometry in neonatal rats of diabetic mothers. Vet Arh 2009;80:421-30.
46 Amaral S, Mota PC, Lacerda B, Alves M, Pereira Mde L, Oliveira PJ, et al. Testicular mitochondrial alterations in untreated streptozotocin-induced diabetic rats. Mitochondrion 2009;9:41-50.   DOI
47 Creasy DM. Pathogenesis of male reproductive toxicity. Toxicol Pathol 2001;29:64-76.   DOI
48 Vidal JD, Whitney KM. Morphologic manifestations of testicular and epididymal toxicity. Spermatogenesis 2014;4:e979099.   DOI
49 Mohamed AK, Zaahkouk S, Abo-Elnaga N, Mousa E. Ameliorating effect of olive leaf extract on testes of diabetic young male rats: histopathological and hematological studies. Adv Biol Res 2017;11:56-63.
50 Tao M, Tasdemir C, Tasdemir S, Shahabi A, Liu G. Penile alterations at early stage of type 1 diabetes in rats. Int Braz J Urol 2017;43:753-61.   DOI
51 Davila HH, Magee TR, Vernet D, Rajfer J, Gonzalez-Cadavid NF. Gene transfer of inducible nitric oxide synthase complementary DNA regresses the fibrotic plaque in an animal model of Peyronie's disease. Biol Reprod 2004;71:1568-77.   DOI
52 Gonzalez-Cadavid NF, Rajfer J. Mechanisms of disease: new insights into the cellular and molecular pathology of Peyronie's disease. Nat Clin Pract Urol 2005;2:291-7.   DOI
53 Mou X, Zhou DY, Zhou DY, Ma JR, Liu YH, Chen HP, et al. Serum $TGF-{\beta}$1 as a biomarker for type 2 diabetic nephropathy: a metaanalysis of randomized controlled trials. PLoS One 2016;11:e0149513.   DOI
54 Liu GL, Zhang YM, Dai DZ, Ding MJ, Cong XD, Dai Y. Male hypogonadism induced by high fat diet and low dose streptozotocin is mediated by activated endoplasmic reticulum stress and $I{\kappa}B{\beta}$ and attenuated by argirein and valsartan. Eur J Pharmacol 2013;713:78-88.   DOI
55 Sonmez MF, Kilic E, Karabulut D, Cilenk K, Deligonul E, Dundar M. Nitric oxide synthase in diabetic rat testicular tissue and the effects of pentoxifylline therapy. Syst Biol Reprod Med 2016;62:22-30.   DOI
56 Kim ST, Moley KH. Paternal effect on embryo quality in diabetic mice is related to poor sperm quality and associated with decreased glucose transporter expression. Reproduction 2008;136:313-22.   DOI
57 Butchi Akondi R, Kumar P, Annapurna A, Pujari M. Protective effect of rutin and naringin on sperm quality in streptozotocin (STZ) induced type 1 diabetic rats. Iran J Pharm Res 2011;10:585-96.
58 Singh AK, Tomarz S, Chaudhari AR, Sinqh R, Verma N. Type 2 diabetes mellitus affects male fertility potential. Indian J Physiol Pharmacol 2014;58:403-6.
59 Ballester J, Munoz MC, Dominguez J, Rigau T, Guinovart JJ, Rodriguez-Gil JE. Insulin-dependent diabetes affects testicular function by FSH- and LH-linked mechanisms. J Androl 2004;25:706-19.   DOI
60 Kianifard D, Sadrkhanlou RA, Hasanzadeh S. The ultrastructural changes of the sertoli and leydig cells following streptozotocin induced diabetes. Iran J Basic Med Sci 2012;15:623-35.
61 Rato L, Alves MG, Dias TR, Cavaco JE, Oliveira PF. Testicular metabolic reprogramming in neonatal streptozotocin-induced type 2 diabetic rats impairs glycolytic flux and promotes glycogen synthesis. J Diabetes Res 2015;2015:973142.   DOI
62 Oliveira PF, Tomas GD, Dias TR, Martins AD, Rato L, Alves MG, et al. White tea consumption restores sperm quality in prediabetic rats preventing testicular oxidative damage. Reprod Biomed Online 2015;31:544-56.   DOI
63 Rabbani SI, Devi K, Khanam S. Pioglitazone, a PPAR-gamma ligand inhibited the nicotinamide-streptozotocin induced sperm abnormalities in type-2 diabetic Wistar rats. Pak J Pharm Sci 2010;23:326-31.
64 Hadi MA, Zaidan HK, Natah TM, Al-Saadi AH. Protective effect of plants extracts mixture on sperm abnormalities, testicular and epididymal tissues in diabetic male rats. J Nat Sci Res 2013;3:28-37.
65 Kilarkaje N, Al-Hussaini H, Al-Bader MM. Diabetes-induced DNA damage and apoptosis are associated with poly (ADP ribose) polymerase 1 inhibition in the rat testis. Eur J Pharmacol 2014;737:29-40.   DOI
66 Mendoza-Lujambio I, Burfeind P, Dixkens C, Meinhardt A, Hoyer-Fender S, Engel W, et al. The Hook1 gene is non-functional in the abnormal spermatozoon head shape (azh) mutant mouse. Hum Mol Genet 2002;11:1647-58.   DOI
67 Yeung CH, Tuttelmann F, Bergmann M, Nordhoff V, Vorona E, Cooper TG. Coiled sperm from infertile patients: characteristics, associated factors and biological implication. Hum Reprod 2009;24:1288-95.   DOI
68 Choi H, Han C, Jin S, Kwon JT, Kim J, Jeong J, et al. reduced fertility and altered epididymal and sperm integrity in mice lacking ADAM7. Biol Reprod 2015;93:70.   DOI
69 Narayana K, D'Souza UJ, Seetharama Rao KP. Ribavirin-induced sperm shape abnormalities in Wistar rat. Mutat Res 2002;513:193-6.   DOI
70 Cheon YP, Cho HJ, Kim KS. Spermatozoa characteristics of streptozotocin-induced diabetic Zucker lean rat: calcium ionophore-induced acrosome reaction and sperm concentration. Korean J Lab Anim Sci 1998;14;15-20.
71 Sisman AR, Kiray M, Camsari UM, Evren M, Ates M, Baykara B, et al. Potential novel biomarkers for diabetic testicular damage in streptozotocin-induced diabetic rats: nerve growth factor Beta and vascular endothelial growth factor. Dis Markers 2014;2014:108106.   DOI
72 Cheon YP, Kim CH, Kang BM, Chang YS, Nam JH, Kim YS, et al. Spermatozoa characteristics of streptozotocin-induced diabetic Wistar rat: acrosome reaction and spermatozoa concentration. Korean J Fertil Steril 1999;26:89-96.
73 Fan Y, Liu Y, Xue K, Gu G, Fan W, Xu Y, et al. Diet-induced obesity in male C57BL/6 mice decreases fertility as a consequence of disrupted blood-testis barrier. PLoS One 2015;10:e0120775.   DOI
74 Ayer-LeLievre C, Olson L, Ebendal T, Hallbook F, Persson H. Nerve growth factor mRNA and protein in the testis and epididymis of mouse and rat. Proc Natl Acad Sci U S A 1988;85:2628-32.   DOI
75 Jin W, Tanaka A, Watanabe G, Matsuda H, Taya K. Effect of NGF on the motility and acrosome reaction of golden hamster spermatozoa in vitro. J Reprod Dev 2010;56:437-43.   DOI
76 Ahmadi A, Fajri M, Sadrkhanlou RA, Mokhtari M. Evaluation of epididymal sperm quality, DNA damage and sperm maturation abnormality in streptozotocin-induced diabetic mice. Int J Fertil Steril 2011;5:40.
77 Paasch U, Heidenreich F, Pursche T, Kuhlisch E, Kettner K, Grunewald S, et al. Identification of increased amounts of eppin protein complex components in sperm cells of diabetic and obese individuals by difference gel electrophoresis. Mol Cell Proteomics 2011;10:M110.007187.
78 Talebi AR, Mangoli E, Nahangi H, Anvari M, Pourentezari M, Halvaei I. Vitamin C attenuates detrimental effects of diabetes mellitus on sperm parameters, chromatin quality and rate of apoptosis in mice. Eur J Obstet Gynecol Reprod Biol 2014;181:32-6.   DOI
79 Kim HS, Kang MJ, Kim SA, Oh SK, Kim H, Ku SY, et al. The utility of sperm DNA damage assay using toluidine blue and aniline blue staining in routine semen analysis. Clin Exp Reprod Med 2013;40:23-8.   DOI