DNA Aptamer Raised against Advanced Glycation End Products Improves Sperm Concentration, Motility, and Viability by Suppressing Receptors for Advanced Glycation End Product-Induced Oxidative Stress and Inflammation in the Testes of Diabetic Mice.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Oxidative Stress*/drug effects ; Glycation End Products, Advanced*/metabolism ; Aptamers, Nucleotide*/pharmacology ; Testis*/metabolism ; Testis*/drug effects ; Testis*/pathology ; Receptor for Advanced Glycation End Products*/metabolism ; Diabetes Mellitus, Experimental*/metabolism ; Sperm Motility*/drug effects ; Diabetes Mellitus, Type 2*/metabolism ; Diabetes Mellitus, Type 2*/pathology ; Inflammation*/metabolism ; Inflammation*/pathology; Animals ; Male ; Mice ; Spermatozoa/metabolism ; Spermatozoa/drug effects ; Sperm Count

Type 2 diabetes mellitus (T2DM) is a risk factor for male infertility, but the underlying molecular mechanisms remain unclear. Advanced glycation end products (AGEs) are pathogenic molecules for diabetic vascular complications. Here, we investigated the effects of the DNA aptamer raised against AGEs (AGE-Apt) on testicular and sperm abnormalities in a T2DM mouse model. KK-Ay (DM) and wild-type (non-DM) 4- and 7-week-old male mice were sacrificed to collect the testes and spermatozoa for immunofluorescence, RT-PCR, and histological analyses. DM and non-DM 7-week-old mice were subcutaneously infused with the AGE-Apt or control-aptamer for 6 weeks and were then sacrificed. Plasma glucose, testicular AGEs, and Rage gene expression in 4-week-old DM mice and plasma glucose, testicular AGEs, oxidative stress, and pro-inflammatory gene expressions in 7-week-old DM mice were higher than those in age-matched non-DM mice, the latter of which was associated with seminiferous tubular dilation. AGE-Apt did not affect glycemic parameters, but it inhibited seminiferous tubular dilation, reduced the number of testicular macrophages and apoptotic cells, and restored the decrease in sperm concentration, motility, and viability of 13-week-old DM mice. Our findings suggest that AGEs-Apt may improve sperm abnormality by suppressing AGE-RAGE-induced oxidative stress and inflammation in the testes of DM mice.

Lab Invest. 2014 Apr;94(4):422-9. (PMID: 24514068)
Fertil Steril. 2005 Jun;83(6):1665-73. (PMID: 15950634)
Molecules. 2019 Mar 07;24(5):. (PMID: 30866536)
Cell Metab. 2018 Sep 4;28(3):337-352. (PMID: 30184484)
J Neuropathol Exp Neurol. 2000 Dec;59(12):1094-105. (PMID: 11138929)
Front Endocrinol (Lausanne). 2018 May 25;9:268. (PMID: 29887834)
Biol Reprod. 2019 Mar 1;100(3):849-861. (PMID: 30398566)
Fertil Steril. 1979 May;31(5):531-7. (PMID: 446777)
Free Radic Biol Med. 2010 Jan 1;48(1):112-9. (PMID: 19837155)
J Virol. 2020 Apr 16;94(9):. (PMID: 32102878)
Horm Metab Res. 2015 Apr;47(4):253-8. (PMID: 25105541)
Reproduction. 2012 Mar;143(3):333-46. (PMID: 22187670)
Diabetes. 2013 Sep;62(9):3241-50. (PMID: 23630304)
Andrology. 2021 Mar;9(2):610-617. (PMID: 33231922)
Ophthalmic Res. 2015;54(4):175-80. (PMID: 26492350)
Cureus. 2021 Jul 9;13(7):e16288. (PMID: 34381648)
Arab J Urol. 2019 Apr 24;17(2):87-97. (PMID: 31285919)
Antioxidants (Basel). 2022 Feb 02;11(2):. (PMID: 35204189)
Am J Reprod Immunol. 2015 Nov;74(5):457-66. (PMID: 26287267)
Int Immunopharmacol. 2021 Dec;101(Pt B):107598. (PMID: 34233864)
Endocrinology. 1997 Mar;138(3):1190-3. (PMID: 9048626)
J Biol Chem. 2002 Jun 7;277(23):20309-15. (PMID: 11912219)
Biochem J. 2011 Jun 15;436(3):687-98. (PMID: 21470189)
Int Urol Nephrol. 2009 Dec;41(4):777-84. (PMID: 19381857)
Asian J Androl. 2014 Jul-Aug;16(4):572-80. (PMID: 24713828)
Diabetes Res Clin Pract. 2007 Sep;77 Suppl 1:S30-40. (PMID: 17462779)
Microvasc Res. 2007 Jul;74(1):65-9. (PMID: 17493639)
Andrologia. 2012 May;44 Suppl 1:490-8. (PMID: 21806668)
In Vivo. 2013 Jul-Aug;27(4):465-72. (PMID: 23812216)
FASEB J. 2003 Sep;17(12):1762-4. (PMID: 12958202)
Hum Reprod. 2017 Jan;32(1):18-31. (PMID: 27864361)
Methods Mol Biol. 2013;927:299-307. (PMID: 22992924)
Asian J Androl. 2013 Jul;15(4):523-8. (PMID: 23728587)
Andrologia. 2017 Dec;49(10):. (PMID: 28124476)
Diabetes. 2017 Jun;66(6):1683-1695. (PMID: 28385802)
Tissue Barriers. 2013 Apr 1;1(2):e23992. (PMID: 24665384)
Hum Reprod. 2007 Jul;22(7):1871-7. (PMID: 17478459)
Reproduction. 2018 Jan;155(1):R13-R37. (PMID: 28993453)
Int J Mol Sci. 2023 Dec 22;25(1):. (PMID: 38203349)
J Clin Invest. 2005 Dec;115(12):3484-93. (PMID: 16284652)
Diabetes Metab Syndr Obes. 2014 Mar 06;7:95-105. (PMID: 24623985)
Mol Med. 2015 Oct 27;21 Suppl 1:S32-40. (PMID: 26605646)
Diabetes Care. 2023 Jan 1;46(Suppl 1):S19-S40. (PMID: 36507649)
Front Endocrinol (Lausanne). 2014 Dec 01;5:205. (PMID: 25520703)
Am J Anat. 1956 Nov;99(3):507-16. (PMID: 13402729)
J Reprod Dev. 2019 Oct 23;65(5):467-473. (PMID: 31447476)
Cent European J Urol. 2013;66(1):60-7. (PMID: 24578993)
Eur Endocrinol. 2014 Aug;10(2):106-110. (PMID: 29872473)
Endocrinology. 1999 Feb;140(2):732-8. (PMID: 9927300)
Diab Vasc Dis Res. 2019 Nov;16(6):556-561. (PMID: 31375034)
Mol Cell Proteomics. 2011 Aug;10(8):M110.007187. (PMID: 21525168)
Biomedicines. 2023 Nov 22;11(12):. (PMID: 38137333)
Fertil Steril. 2008 May;89(5):1183-1190. (PMID: 17669405)
Cardiovasc Diabetol. 2019 Oct 31;18(1):143. (PMID: 31672147)
J Reprod Infertil. 2015 Jul-Sep;16(3):123-9. (PMID: 26913230)
Nutr Diabetes. 2020 Jul 2;10(1):24. (PMID: 32616730)
Development. 2019 Apr 23;146(8):. (PMID: 30936178)
J Clin Endocrinol Metab. 2004 Nov;89(11):5462-8. (PMID: 15531498)
Fertil Steril. 2003 Sep;80(3):531-5. (PMID: 12969693)
Biomed Res Int. 2015;2015:732450. (PMID: 26114112)
Exp Anim. 2002 Apr;51(2):191-6. (PMID: 12012732)
Reprod Biol Endocrinol. 2004 Mar 23;2:12. (PMID: 15038829)
Diabetologia. 2003 Feb;46(2):284-7. (PMID: 12627328)
Toxicol Pathol. 2001 Jan-Feb;29(1):64-76. (PMID: 11215686)
Crit Rev Eukaryot Gene Expr. 2010;20(2):87-103. (PMID: 21133840)
J Clin Immunol. 2007 Mar;27(2):152-62. (PMID: 17308869)
Toxicol Pathol. 2013;41(4):615-27. (PMID: 23197197)
Microvasc Res. 2013 Nov;90:64-70. (PMID: 24012635)
Int J Biochem Cell Biol. 2016 Dec;81(Pt B):403-418. (PMID: 27373680)
J Hum Reprod Sci. 2015 Oct-Dec;8(4):191-6. (PMID: 26752853)
Br J Pharmacol. 2020 Aug;177(16):3617-3624. (PMID: 32662519)
Circ J. 2019 Aug 23;83(9):1822-1828. (PMID: 31366777)
Biol Pharm Bull. 2007 Jan;30(1):84-90. (PMID: 17202665)

22K15031 Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; 24K12518 Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; Research Grant Award 2021 Japanese Society of Anti-Aing Medicine; Grants for young researchers Japan Association for Diabetes Education and Care

Keywords: AGEs; DNA aptamer; diabetes; male infertility; sperm abnormality; testis

0 (Glycation End Products, Advanced)
0 (Aptamers, Nucleotide)
0 (Receptor for Advanced Glycation End Products)

Date Created: 20240619 Date Completed: 20240619 Latest Revision: 20240620

20240620

PMC11172898

10.3390/ijms25115947

38892134