Objectives: To investigate the effects of diabetes on the reproductive system andextracellular matrix proteins of diabetic rats. Materials and Methods: Wistar albinomale rats, body weight (BW) 160-200 g, were divided into two groups: I -streptozoticin diabetes, II - normal non-diabetic animals. The content of amino acidsin rat type I collagen was determined using an amino acid analyzer. Morphologicalanalyses of gonadic structures were carried out by an optic microscope. Results: Thestudy of the effects of diabetes on type I collagen amino acid content, testis cellsmorphologic and morphometric parameters and spermatogenesis demonstrated thepresence of diabetes-mediated quantitative and qualitative changes in male ratreproductive organs, spermatogenetic epithelial cells and extracellular matrixproteins in comparison with normal. Conclusions: Observed collagen moleculeschanges could hence affect the properties and correct functioning of spermatogeneticepithelium and of other tissues of reproductive organs. They could be caused bydiabetes via deficiency of insulin which is involved in collagen synthesis regulationat different stages of this process, cytochrome P450-2E1 induction and reactiveoxygen species effects on protein biosynthesis processes.
1. Mladovsky P, Allin S, Masseria C et al. Health in the European Union. Trends and Analysis. Observatory Studies Series № 19. Publications, World Health Organization Regional Office for Europe, Copenhagen, pp 200, 2009. (http://www.euro.who.int/pubrequest).
2. American Diabetes Association. Diabetic nephropathy. Diabetes Care 24[Suppl 1]:S69-S72, 2001.
3. Ramalho-Santos J, Amaral S, Oliveria PJ. Diabetes and the impairment of reproductive function: Possible role of mitochondria and reactive oxygen species. Curr Diabetes Rev 4:46-54, 2008.
4. Agbaje IM, Rogers DA, McVicar CM et al. Insulin dependent diabetes mellitus: implications for male reproductive function. Hum Reprod 22: 1871-1877, 2007.
5. Nieto N, Friedman SL, Cederbaum AI. Cytochrome P450 2E1-derived reactive oxygen species mediate paracrine stimulation of collagen I protein synthesis by hepatic stellate cells. J Biol Chem 277: 9853-9864, 2002.
6. Lehti T M, Silvennoinen M, Kivela R et al. Effects of streptozotocin-induced diabetes and physical training on gene expression of extracellular matrix proteins in mouse skeletal muscle. Am J Physiol Endocrinol Metab 290:E900-E907, 2006.
7. Bembenk ME, Liberti JP. The anabolic effects of insulin on type II collagen synthesis of Swarm rat chondrosarcoma chondrocytes. Arch Biochem Biophys 233: 203-211, 1984.
8. Pallante KM, Niu Z, Zhao Y et al. The chick 2 (I) collagen gene contains two functional promoters, and its expression in chondrocytes is regulated at both transcriptional and post-transcriptional levels. J Biol Chem 271: 25233-25239, 1996.
9. Bondarenko LB, Shayakhmetova GM, Byshovets TF, Kovalenko VM. Pyrazinamidemediated changes in rat type I collagen and spermatogenesis indices. Acta Pol Pharm 68: 285-290, 2011.
10. Sricharoenvej S, Tongpob Y, Lanlua P, et al. Renal microvascular changes in streptozotocin-induced, long-termed diabetic rat. J Med Assoc Thai 90: 2677-2682, 2007
11. Trelstad RL, Catanese VM, Rubin DF. Collagen fractionation: separation of native types I, II and III by differential precipitation. Anal Biochem 71:114-118, 1976
12. Rubin AL, Drake MP, Davison PF et al. Effect of pepsin on the interaction properties of tropocollagen macromolecules. Biochemistry 4: 181-190, 1965.
13. Maurer G. The Disk-electrophoresis, Mir, Moscow, p. 247, 1971 (in Russian).
14. Deveni T, Gherghey J. The amino-acids, peptides and proteins, Mir, Moscow, p. 364, 1976 (in Russian).
15. Boekelheide K, Chapin R. Male reproductive toxicology. In Current Protocols in Toxicology, Costa LG, Hodgson E, Lawrence DA, Ozolins TR, Reed DJ, Greenlee WF Eds., John Wiley & Sons, Inc, pp. 16.0.1-16.0.2, 2005.
16. El'tseva TV, Adamskaya EI, Peryshkova TA, Babichev VN. Disturbance of neuroendocrine regulation of sexual behavior of male rats with streptozotocin diabetes. Neurosci Behav Physiol 23: 538-544, 1993.
17. Ramachandran GN. Biochemistry of collagen. Plenum Press, New York, London pp. 536, 1976.
18. Yavuz D, Tugtepe H, Cetinel S et al. Collagen ultrastructure and TGF-beta1 expression preserved with amino guanidine during wound healing in diabetic rats. Endocr Res 31: 229-243, 2005.
19. Kim BM, Eichler J, Reiser KM et al. Collagen structure and nonlinear susceptibility: effects of heat, glycation, and enzymatic cleavage on second harmonic signal intensity. Lasers Surg Med 27: 329-335, 2000.
20. Chamberlain JR, Schwarze U, Wang PR et al. Gene targeting in stem cells from individuals with osteogenesis imperfect. Science 303: 1198-1201, 2004.
21. He Z, Feng L, Zhang X et al. Expression of Col1a1, Col1a2 and procollagen I in germ cells of immature and adult mouse testis. Reproduction 130: 333-341, 2005.
22. Nakamura F, Suyama K. An amino acid derived from aldol crosslink of elastin and collagen: structure, distribution, aging, and two models of hyperglycemia. Arch Biochem Biophys 325: 167-173, 1996.
23. Avery NC, Bailey Aj. The effects of the Maillard reaction on the physical properties and cell interactions of collagen. Pathol Biol (Paris) 54: 387-395, 2006.
24. Hadley JC, Meek KM, Malik NS. Glycation changes the charge distribution of type I collagen fibrils. Glycoconj J 15: 835-840, 1998.
25. Pedchenko VK, Chetyrkyn SV, Chuang P, Ham AJ. Mechanism of perturbation of integrinmediated cell-matrix interactions by reactive carbonyl compounds and its implication for pathogenesis of diabetic nephropathy. Diabetes 54: 2952-2960, 2005.
26. Kornblihtt AR, Gutman A. Molecular biology of the extracellular matrix proteins. Biol Rev Camb Philos Soc 63: 465-507, 1988.
27. Van der Rest M, Garrone R. Collagen family of proteins. FASEB J 5: 2814-2823, 1991.
28. Loeser RF, Wallin R. Cell adhesion to matrix Gla protein and its inhibition by an Arg-Gly-Aspcontaining peptide. J Biol Chem 267:9459-9462, 1992.
29. Koide T, Takahara Y, Asada S, Nagata K. Xaa-Arg-Gly triplets in the collagen triple helix are dominant binding sites for the molecular chaperone HSP47 J Biol Chem 277: 6178-6182, 2002.
30. Kato M, Zhang J. Wang M et al. MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors. Proc Natl Acad Sci USA 104: 3432-3437, 2007.
31. Knoll KE, Pietrusz JL Liang M. Tissuespecific transcriptome responses in rats with early streptozotocin-induced diabetes. Physiol Genomics 21: 222-229, 2005.
32. Bondarenko LB, Saprykina NA, Kovalenko VM. Lung and spleen contents of free amino acids after pyrazinamide treatment. Acta Toxicologica 14:79-86, 2006.
33. Fox HL, Kimbell SR, Jefferson LS, Lynch CJ. Amino acids stimulate phosphorylation of p70s6k and organisation of rat adipocytes into multicellular clusters. Am J Physiol 274: C206-C213, 1998.
34. Inamasu J, Guiot BH, Sachs DC. Ossification of the posterior longitudinal ligament: an update on its biology, epidemiology, and natural history. Neurosurgery 58: 1027-1039, 2006.
35. Lee B, D’Alessio M, Vissing H et al. Characterization of large deletion associated with polymorphic block of repeated dinucleotide in the type III procollagen gene (COL 3A1) of patient with Ehlers-Dahnlos syndrome type IV. Amer J Hum Genet. 48: 511-517, 1991.
36. Wirtz MK, Rao VH, Glanville RW et al. A cysteine for glycine substitution at position 175 in an 1(I)-chain of type I collagen at clinically heterogenous form of osteogenesis imperfecta. Connect Tissue Res 29: 1-11, 1993.
37. Sapone A, Affatato A, Canistro D et al. Induction and suppression of cytochrome P450 isoenzymes and generation of oxygen radicals by procymidone in liver, kidney and lung of CD1 mice. Mutat Res 527: 67-80, 2003.