Senil infertilitede genç plazmanın yaşa bağlı testiküler dejenerasyonu tersine çevirdiğine dair spektrokimyasal kanıtlar

Abstract

Amaç: Yaşlı erkeklerde görülen infertilite esas olarak testis dejenerasyonu ile ilişkilidir; ancak bu durumun kesin etiyolojisi hâlâ netlik kazanmamıştır. Son yıllarda, yaşa bağlı fizyolojik bozulmaları hafifletmeye yönelik stratejilere artan bir ilgi vardır. Bu çalışma, yaşlı ve genç Wistar sıçanlar arasında gerçekleştirilen heterokronik kan plazması değişiminin, testis dokusunun moleküler bileşimi üzerindeki potansiyel iyileştirici etkilerini araştırmayı amaçlamaktadır. Özellikle protein, lipit, karbonhidrat ve nükleik asit profilleri hedeflenmiştir. Yöntem: Spektral veriler Fourier Dönüşümlü Kızılötesi (FTIR) spektroskopisi ile elde edilmiş ve Temel Bileşenler Analizi (PCA) ile değerlendirilmiştir. Bulgular: Genç testis dokularının spektral özellikleriyle karşılaştırıldığında, yaşlı örneklerde yapısal dejenerasyona işaret eden belirgin moleküler değişiklikler gözlemlenmiştir. Bu değişiklikler arasında spektral omuz oluşumu, bant genişlemesi ve özellikle β-tabaka açısından zengin protein konformasyonları ile ilişkili frekans kaymaları yer almaktadır. Fosfolipit ve glikolipitlerle ilişkili bantlar, yaşlı kontrol grubu ile yaşlı plazması verilen genç grupta gözlenirken, genç kontrol ve genç plazması verilen yaşlı gruplarda bu bantlar bulunmamıştır. Benzer şekilde, testiküler glikojen, metil salınımı ve nükleik asit fosfat gruplarına ait spektral özellikler yaşlı dokularda kaybolmuş, ancak genç ve genç plazması verilen yaşlı örneklerde korunmuştur. Bu değişiklikler istatistiksel olarak anlamlı bulunmuştur (p < 0.01, %99 güven aralığı). Sonuç: Plazma değişimi, alıcı testis dokusunda bağışçıya özgü moleküler imzaları yansıtan spektroskopik olarak saptanabilir değişikliklere neden olmuştur. Protein ikincil yapıların yeniden oluşumu ve nükleik asit ile glikojenle ilişkili spektral sinyallerin yeniden ortaya çıkışı, genç plazmanın yaşa bağlı erkek üreme sistemindeki dejenerasyona karşı terapötik potansiyel taşıdığını ortaya koymaktadır.

Keywords

• Senil infertilite
• testis dokusu
• genç plazma
• FTIR ile moleküler profil
• spektroskopi
• PCA modellemesi

Spectrochemical evidence for the reversal of age-related testicular degeneration by young plasma in senile infertility

Abstract

Aims: Senile infertility in males is primarily associated with testicular degeneration, although its precise etiology remains unclear. In recent years, increasing attention has been directed toward strategies aimed at ameliorating age-related physiological deterioration. The present study investigates the potential restorative effects of heterochronic blood plasma exchange between aged and young Wistar rats on the molecular composition of testicular tissue specifically targeting protein, lipid, carbohydrate, and nucleic acid profiles. Methods: Spectral data were acquired via fourier transform infrared (FTIR) spectroscopy and evaluated through principal component analysis (PCA). Results: Compared to the spectral characteristics of young testicular tissue, aged samples exhibited prominent molecular alterations indicative of structural degeneration, including spectral shoulder formation, band broadening, and frequency shifts—particularly associated with β-sheet-rich protein conformations. Notably, phospholipid and glycolipid-associated bands were present in aged controls and young rats receiving aged plasma, but absent in young controls and aged rats treated with young plasma. Similarly, spectral features related to testicular glycogen, methyl rocking, and nucleic acid phosphate groups were lost in aged tissues but preserved in young and rejuvenated aged samples. These alterations were statistically significant (p<0.01, 99% confidence). Conclusion: Overall, plasma exchange induced spectroscopically detectable modifications that reflect donor-specific molecular signatures in recipient testicular tissue. Restoration of protein secondary structures and reappearance of nucleic acid and glycogen-associated signals in aged rats receiving young plasma underscore the therapeutic potential of this intervention against male reproductive aging. Nevertheless, as this study was designed as an FTIR-centered spectrochemical analysis, it does not address deeper molecular layers such as proteomics or RNA-seq, the durability of plasma-induced effects over longer periods, or the potential applicability to the female reproductive system. Future studies are warranted to explore these dimensions and further strengthen translational relevance.

Keywords

• Senile infertility
• testicle tissue
• young plasma
• molecule profile FTIR
• spectroscopy
• PCA modeling

References

1. Teker HT, Ceylani T, Keskin S, et al. Age-related differences in response to plasma exchange in male rat liver tissues: insights from histopathological and machine-learning assisted spectrochemical analyses. Biogerontology. 2023;24(4):563-580. doi:10.1007/s10522-023-10032-3
2. Gonskikh Y, Polacek N. Alterations of the translation apparatus during aging and stress response. Mech Ageing Dev. 2017;168:30-36. doi:10. 1016/j.mad.2017.04.003
3. Krisko A, Radman M. Protein damage, ageing and age-related diseases. Open Biol. 2019;9(3):180249. doi:10.1098/rsob.180249
4. Ceylani T, Teker HT, Keskin S, Samgane G, Acikgoz E, Gurbanov R. The rejuvenating influence of young plasma on aged intestine. J Cell Mol Med. 2023;27(18):2804-2816. doi:10.1111/jcmm.17926
5. Anisimova AS, Alexandrov AI, Makarova NE, Gladyshev VN, Dmitriev SE. Protein synthesis and quality control in aging. Aging (Albany NY). 2018;10(12):4269-4288. doi:10.18632/aging.101721
6. Belsky DW, Caspi A, Houts R, et al. Quantification of biological aging in young adults. Proc Natl Acad Sci U S A. 2015;112(30):E4104-10. doi:10. 1073/pnas.1506264112
7. Bektas A, Schurman SH, Sen R, Ferrucci L. Aging, inflammation and the environment. Exp Gerontol. 2018;105:10-18. doi:10.1016/j.exger.2017. 12.015
8. Mazur DJ, Lipshultz LI. Infertility in the aging male. Curr Urol Rep. 2018;19(7):54. doi:10.1007/s11934-018-0802-3

9. Kidd SA, Eskenazi B, Wyrobek AJ. Effects of male age on semen quality and fertility: a review of the literature. Fertil Steril. 2001;75(2):237-248. doi:10.1016/s0015-0282(00)01679-4
10. İlhan F. Evcil hayvanlarda testis dejenerasyonları. Yüzüncü Yıl Üniversitesi Vet Fakültesi Derg. 2003;14(2):51-56.
11. Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature. 2005;433(7027):760-764. doi:10.1038/nature03260
12. Villeda SA, Plambeck KE, Middeldorp J, et al. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat Med. 2014;20(6):659-663. doi:10.1038/nm.3569
13. Liu A, Guo E, Yang J, et al. Young plasma reverses age-dependent alterations in hepatic function through the restoration of autophagy. Aging Cell. 2018;17(1):e12708. doi:10.1111/acel.12708
14. Erdogan K, Ceylani T, Teker HT, Sengil AZ, Uysal F. Young plasma transfer recovers decreased sperm counts and restores epigenetics in aged testis. Exp Gerontol. 2023;172(August):112042. doi:10.1016/j.exger. 2022.112042
15. Ceylani T, Teker HT, Samgane G, Gurbanov R. Intermittent fasting-induced biomolecular modifications in rat tissues detected by ATR-FTIR spectroscopy and machine learning algorithms. Anal Biochem. 2022;654:114825. doi:10.1016/j.ab.2022.114825
16. Severcan F, Haris PI. Vibrational Spectroscopy in Diagnosis and Screening. Vol 6. IOS Press; 2012.
17. Nieuwoudt HH, Prior BA, Pretorius IS, Manley M, Bauer FF. Principal component analysis applied to Fourier transform infrared spectroscopy for the design of calibration sets for glycerol prediction models in wine and for the detection and classification of outlier samples. J Agric Food Chem. 2004;52(12):3726-3735. doi:10.1021/jf035431q
18. Barth A. Infrared spectroscopy of proteins. Biochim Biophys Acta-Bioenerg. 2007;1767(9):1073-1101. doi:10.1016/j.bbabio.2007.06.004
19. Sato H, Morisawa Y, Takaya S, Ozaki Y. A Study of C=O…HO and OH…OH (dimer, trimer, and oligomer) hydrogen bonding in a poly(4-vinylphenol) 30%/poly(methyl methacrylate) 70% blend and its thermal behavior using near-infrared spectroscopy and infrared spectroscopy. Appl Spectrosc. 2022;76:831-840. doi:10.1177/00037028221086913
20. Endo J, Suzuki Y. Reassessment of vibration spectra in alkali phosphate crystals. J Ceram Soc Japan. 2022;130(4):324-326. doi:10.2109/jcersj2.21180
21. Frost R, Scholz R, López A, Firmino B, Lana C, Xi Y. A Raman and infrared spectroscopic characterisation of the phosphate mineral phosphohedyphane Ca(2)Pb(3)(PO(4))(3)Cl from the Roote mine, Nevada, USA. Spectrochim Acta A Mol Biomol Spectrosc. 2014;127:237-242. doi:10.1016/j.saa.2014.02.067
22. Yano K, Ohoshima S, Gotou Y, Kumaido K, Moriguchi T, Katayama H. Direct measurement of human lung cancerous and noncancerous tissues by fourier transform infrared microscopy: can an infrared microscope be used as a clinical tool? Anal Biochem. 2000;287(2):218-225. doi:10.1006/ABIO.2000.4872
23. Bel’skaya L, Sarf E, Solomatin D. Determination of the quantitative content of lipids in a biological material by the method of IR spectroscopy. Klin Lab Diagn. 2019;64(4):204-209. doi:10.18821/0869-2084-2019-64-4-204-209
24. Tripathi SS, Kumar R, Arya JK, Rizvi SI. Plasma from young rats injected into old rats induce antiaging effects. Rejuvenation Res. 2021;24(3):206-212. doi:10.1089/rej.2020.2354
25. Adienbo OM, Nwafor A, Dapper DV. Impairments in testicular function indices in male wistar rats: a possible mechanism for infertility induction by Xylopia aethiopica fruit extract. Int J Reprod Contraception, Obstet Gynecol. 2017;4(1):71-75.
26. Villarroel-Espíndola F, Maldonado R, Mancilla H, et al. Muscle glycogen synthase isoform is responsible for testicular glycogen synthesis: glycogen overproduction induces apoptosis in male germ cells. J Cell Biochem. 2013;114(7):1653-1664. doi:10.1002/jcb.24507
27. Taner H, Taha T, Seda C, Gizem K, Sina S, Burcu M. Age related differences in response to plasma exchange in male rat liver tissues: insights from histopathological and machine learning assisted spectrochemical analyses. Biogerontology. 2023;24(4):563-580. doi:10. 1007/s10522-023-10032-3
28. Ferlin A, Foresta C. New genetic markers for male infertility. Curr Opin Obstet Gynecol. 2014;26(3):193-198. doi:10.1097/GCO.0000000000000061
29. Oakes CC, Smiraglia DJ, Plass C, Trasler JM, Robaire B. Aging results in hypermethylation of ribosomal DNA in sperm and liver of male rats. Proc Natl Acad Sci U S A. 2003;100(4):1775-1780. doi:10.1073/pnas. 0437971100
30. Rotondo JC, Lanzillotti C, Mazziotta C, Tognon M, Martini F. Epigenetics of male infertility: the role of DNA methylation. Front cell Dev Biol. 2021;9:689624. doi:10.3389/fcell.2021.689624
31. Baba B, Ceylani T, Gurbanov R, et al. Promoting longevity in aged liver through NLRP3 inflammasome inhibition using tauroursodeoxycholic acid (TUDCA) and SCD probiotics. Arch Gerontol Geriatr. 2024;125: 105517. doi:10.1016/j.archger.2024.105517
32. Ceylani T, Allahverdi H, Teker HT. Role of age-related plasma in the diversity of gut bacteria. Arch Gerontol Geriatr. 2023;111:105003. doi:10. 1016/j.archger.2023.105003