Skip to main content

Advertisement

SpringerLink
Log in

Testicular Toxicity in Rats Exposed to AlCl3: a Proteomics Study

  • Research
  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Aluminum contamination is a growing environmental and public health concern, and aluminum testicular toxicity has been reported in male rats; however, the underlying mechanisms of this toxicity are unclear. The objective of this study was to investigate the effects of exposure to aluminum chloride (AlCl3) on alterations in the levels of sex hormones (testosterone [T], luteinizing hormone [LH], and follicle-stimulating hormone [FSH]) and testicular damage. Additionally, the mechanisms of toxicity in the testes of AlCl3-exposed rats were analyzed by proteomics. Three different concentrations of AlCl3 were administered to rats. The results demonstrated a decrease in T, LH, and FSH levels with increasing concentrations of AlCl3 exposure. HE staining results revealed that the spermatogenic cells in the AlCl3-exposed rats were widened, disorganized, or absent, with increased severe tissue destruction at higher concentrations of AlCl3 exposure. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses revealed that differentially expressed proteins (DEPs) after AlCl3 exposure were primarily associated with various metabolic processes, sperm fibrous sheath, calcium-dependent protein binding, oxidative phosphorylation, and ribosomes. Subsequently, DEPs from each group were subjected to protein-protein interaction (PPI) analysis followed by the screening of interactional key DEPs. Western blot experiments validated the proteomics data, revealing the downregulation of sperm-related DEPs (AKAP4, ODF1, and OAZ3) and upregulation of regulatory ribosome-associated protein (UBA52) and mitochondrial ribosomal protein (MRPL32). These findings provide a basis for studying the mechanism of testicular toxicity due to AlCl3 exposure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

Data Availability

All data will be provided upon request.

References

  1. Chen H, Chow CL, Lau D (2022) Deterioration mechanisms and advanced inspection technologies of aluminum windows. Materials 15:354. https://doi.org/10.3390/ma15010354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Chauhan DK, Yadav V, Vaculík M et al (2021) Aluminum toxicity and aluminum stress-induced physiological tolerance responses in higher plants. Crit Rev Biotechnol 41:715–730. https://doi.org/10.1080/07388551.2021.1874282

    Article  CAS  PubMed  Google Scholar 

  3. Liu Q, Zhou L, Liu F et al (2019) Uptake and subcellular distribution of aluminum in a marine diatom. Ecotoxicol Environ Saf 169:85–92. https://doi.org/10.1016/j.ecoenv.2018.10.095

    Article  CAS  PubMed  Google Scholar 

  4. Shetty R, Vidya CS-N, Prakash NB et al (2021) Aluminum toxicity in plants and its possible mitigation in acid soils by biochar: a review. Sci Total Environ 765:142744. https://doi.org/10.1016/j.scitotenv.2020.142744

    Article  CAS  PubMed  Google Scholar 

  5. Wang D, He Y, Liang J et al (2013) Distribution and source analysis of aluminum in rivers near Xi’an City, China. Environ Monit Assess 185:1041–1053. https://doi.org/10.1007/s10661-012-2612-2

    Article  CAS  PubMed  Google Scholar 

  6. Makhdoomi S, Ariafar S, Mirzaei F, Mohammadi M (2023) Aluminum neurotoxicity and autophagy: a mechanistic view. Neurol Res 45:216–225. https://doi.org/10.1080/01616412.2022.2132727

    Article  CAS  PubMed  Google Scholar 

  7. Ahmed WMS, Ibrahim MA, Helmy NA et al (2022) Amelioration of aluminum-induced hepatic and nephrotoxicity by Premna odorata extract is mediated by lowering MMP9 and TGF-β gene alterations in Wistar rat. Environ Sci Pollut Res 29:72827–72838. https://doi.org/10.1007/s11356-022-20735-8

    Article  CAS  Google Scholar 

  8. Zhou L, He M, Li X et al (2022) Molecular mechanism of aluminum-induced oxidative damage and apoptosis in rat cardiomyocytes. Biol Trace Elem Res 200:308–317. https://doi.org/10.1007/s12011-021-02646-w

    Article  CAS  PubMed  Google Scholar 

  9. Yuan H-X, Pang Y-F, Wang J-L, Chen W-C (2019) Impacts of aluminum on sperm quality and sperm mitochondria in male rats. Zhonghua Nan Ke Xue 25:579–585

    PubMed  Google Scholar 

  10. Miska-Schramm A, Kapusta J, Kruczek M (2017) The effect of aluminum exposure on reproductive ability in the bank vole (Myodes glareolus). Biol Trace Elem Res 177:97–106. https://doi.org/10.1007/s12011-016-0848-3

    Article  CAS  PubMed  Google Scholar 

  11. Cheraghi E, Golkar A, Roshanaei K, Alani B (2017) Aluminium-induced oxidative stress, apoptosis and alterations in testicular tissue and sperm quality in Wistar rats: ameliorative effects of curcumin. Int J fertil Steril 11. https://doi.org/10.22074/ijfs.2017.4859

  12. da Silva LD, da Silva GL, de Sousa FE et al (2020) Aluminum exposure promotes histopathological and pro-oxidant damage to the prostate and gonads of male and female adult gerbils. Exp Mol Pathol 116:104486. https://doi.org/10.1016/j.yexmp.2020.104486

    Article  CAS  PubMed  Google Scholar 

  13. Rozanova S, Barkovits K, Nikolov M et al (2021) Quantitative mass spectrometry-based proteomics: an overview. Methods Mol Biol 2228:85–116. https://doi.org/10.1007/978-1-0716-1024-4_8

    Article  CAS  PubMed  Google Scholar 

  14. McArdle AJ, Menikou S (2021) What is proteomics? Arch Dis Child Educ Pract Ed 106:178–181. https://doi.org/10.1136/archdischild-2019-317434

    Article  PubMed  Google Scholar 

  15. Liu Z, Li Y, Sepúlveda MS et al (2021) Development of an adverse outcome pathway for nanoplastic toxicity in Daphnia pulex using proteomics. Sci Total Environ 766:144249. https://doi.org/10.1016/j.scitotenv.2020.144249

    Article  CAS  PubMed  Google Scholar 

  16. Sun X, Wang Y, Jiang T et al (2021) Nephrotoxicity profile of cadmium revealed by proteomics in mouse kidney. Biol Trace Elem Res 199:1929–1940. https://doi.org/10.1007/s12011-020-02312-7

    Article  CAS  PubMed  Google Scholar 

  17. Yurchenko VV, Morozov AA, Kiriukhin BA (2022) Proteomics analysis in Japanese Medaka Oryzias latipes exposed to humic acid revealed suppression of innate immunity and coagulation proteins. Biology (Basel) 11:683. https://doi.org/10.3390/biology11050683

    Article  CAS  PubMed  Google Scholar 

  18. Khan ZN, Sabino IT, de Souza Melo CG et al (2019) Liver proteome of mice with distinct genetic susceptibilities to fluorosis treated with different concentrations of F in the drinking water. Biol Trace Elem Res 187:107–119. https://doi.org/10.1007/s12011-018-1344-8

    Article  CAS  PubMed  Google Scholar 

  19. Xu F, Liu Y, Zhao H et al (2017) Aluminum chloride caused liver dysfunction and mitochondrial energy metabolism disorder in rat. J Inorg Biochem 174:55–62. https://doi.org/10.1016/j.jinorgbio.2017.04.016

    Article  CAS  PubMed  Google Scholar 

  20. Doyle TJ, Oudes AJ, Kim KH (2009) Temporal profiling of rat transcriptomes in retinol-replenished vitamin A-deficient testis. Syst Biol Reprod Med 55:145–163. https://doi.org/10.3109/19396360902896844

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yang Y, Luo J, Yu D et al (2018) Vitamin A promotes Leydig cell differentiation via alcohol dehydrogenase 1. Front Endocrinol 9:644. https://doi.org/10.3389/fendo.2018.00644

    Article  Google Scholar 

  22. Béziers P, Ducrest A-L, Simon C, Roulin A (2017) Circulating testosterone and feather-gene expression of receptors and metabolic enzymes in relation to melanin-based colouration in the barn owl. Gen Comp Endocrinol 250:36–45. https://doi.org/10.1016/j.ygcen.2017.04.015

    Article  CAS  PubMed  Google Scholar 

  23. Topo E, Soricelli A, D’Aniello A et al (2009) The role and molecular mechanism of D-aspartic acid in the release and synthesis of LH and testosterone in humans and rats. Reprod Biol Endocrinol 7:120. https://doi.org/10.1186/1477-7827-7-120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Santillo A, Falvo S, Chieffi P et al (2016) D-aspartate induces proliferative pathways in spermatogonial GC-1 cells: GC-1 CELL PROLIFERATION INDUCED BY D-Asp. J Cell Physiol 231:490–495. https://doi.org/10.1002/jcp.25095

    Article  CAS  PubMed  Google Scholar 

  25. Morris MB, Ozsoy S, Zada M et al (2020) Selected amino acids promote mouse pre-implantation embryo development in a growth factor-like manner. Front Physiol 11:140. https://doi.org/10.3389/fphys.2020.00140

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ma C, Mirth CK, Hall MD, Piper MDW (2022) Amino acid quality modifies the quantitative availability of protein for reproduction in Drosophila melanogaster. J Insect Physiol 139:104050. https://doi.org/10.1016/j.jinsphys.2020.104050

    Article  CAS  PubMed  Google Scholar 

  27. Ommati MM, Heidari R, Zamiri MJ et al (2020) The footprints of oxidative stress and mitochondrial impairment in arsenic trioxide-induced testosterone release suppression in pubertal and mature F1-male Balb/c mice via the downregulation of 3β-HSD, 17β-HSD, and CYP11a expression. Biol Trace Elem Res 195:125–134. https://doi.org/10.1007/s12011-019-01815-2

    Article  CAS  PubMed  Google Scholar 

  28. Oduwole OO, Peltoketo H, Huhtaniemi IT (2018) Role of follicle-stimulating hormone in spermatogenesis. Front Endocrinol (Lausanne) 9:763. https://doi.org/10.3389/fendo.2018.00763

    Article  PubMed  Google Scholar 

  29. Ozcan Yildirim S, Colakoglu N, Ozer Kaya S (2022) Protective effects of L -arginine against aluminium chloride-induced testicular damage in rats. Andrologia 54. https://doi.org/10.1111/and.14569

  30. Gao D-D, Lan C-F, Cao X-N et al (2022) G protein-coupled estrogen receptor promotes acrosome reaction via regulation of Ca2+ signaling in mouse sperm†. Biol Reprod 107:1026–1034. https://doi.org/10.1093/biolre/ioac136

    Article  PubMed  Google Scholar 

  31. Sato T, Arimura T, Murata K et al (2021) Differences of extracellular cues and Ca2+ permeable channels in the signaling path differences ways for inducing amphibian sperm motility. Zoolog Sci 38:343–351. https://doi.org/10.2108/zs200159

    Article  PubMed  Google Scholar 

  32. Zhou F, Du G, Xie J et al (2020) RyRs mediate lead-induced neurodegenerative disorders through calcium signaling pathways. Sci Total Environ 701:134901. https://doi.org/10.1016/j.scitotenv.2019.134901

    Article  CAS  PubMed  Google Scholar 

  33. Ren T, Tang Y, Wang M et al (2020) Triptolide induces apoptosis through the calcium/calmodulin-dependent protein kinase kinaseβ/AMP-activated protein kinase signaling pathway in non-small cell lung cancer cells. Oncol Rep. https://doi.org/10.3892/or.2020.7763

  34. Ham J, Lim W, You S, Song G (2020) Butylated hydroxyanisole induces testicular dysfunction in mouse testis cells by dysregulating calcium homeostasis and stimulating endoplasmic reticulum stress. Sci Total Environ 702:134775. https://doi.org/10.1016/j.scitotenv.2019.134775

    Article  CAS  PubMed  Google Scholar 

  35. Li Y, Jin L, Li Y et al (2022) Lysophosphatidic acid improves human sperm motility by enhancing glycolysis and activating L-type calcium channels. Front Endocrinol (Lausanne) 13:896558. https://doi.org/10.3389/fendo.2022.896558

    Article  PubMed  Google Scholar 

  36. Liu X, Teng Z, Wang Z et al (2022) Expressions of HSPA1L and HSPA9 are associated with poor sperm quality of low-motility spermatozoa in fertile men. Andrologia 54:e14321. https://doi.org/10.1111/and.14321

    Article  CAS  PubMed  Google Scholar 

  37. Park Y-J, Pang M-G (2021) Mitochondrial functionality in male fertility: from spermatogenesis to fertilization. Antioxidants (Basel) 10:98. https://doi.org/10.3390/antiox10010098

    Article  CAS  PubMed  Google Scholar 

  38. Tang W, Xiao Y, Long Y et al (2021) Sodium fluoride causes oxidative damage to silkworm (Bombyx mori) testis by affecting the oxidative phosphorylation pathway. Ecotoxicol Environ Saf 218:112229. https://doi.org/10.1016/j.ecoenv.2021.112229

    Article  CAS  PubMed  Google Scholar 

  39. da Silva J, Gonçalves RV, de Melo FCSA et al (2021) Cadmium Exposure and testis susceptibility: a systematic review in murine models. Biol Trace Elem Res 199:2663–2676. https://doi.org/10.1007/s12011-020-02389-0

    Article  CAS  PubMed  Google Scholar 

  40. Shih H-J, Chang C-Y, Huang I-T et al (2021) Testicular torsion-detorsion causes dysfunction of mitochondrial oxidative phosphorylation. Andrology 9:1902–1910. https://doi.org/10.1111/andr.13068

    Article  CAS  PubMed  Google Scholar 

  41. Dibley MG, Formosa LE, Lyu B et al (2020) The mitochondrial acyl-carrier protein interaction network highlights important roles for LYRM family members in complex I and mitoribosome assembly. Mol Cell Proteomics 19:65–77. https://doi.org/10.1074/mcp.RA119.001784

    Article  CAS  PubMed  Google Scholar 

  42. Zhang R, Hou T, Cheng H, Wang X (2019) NDUFAB1 protects against obesity and insulin resistance by enhancing mitochondrial metabolism. FASEB J 33:13310–13322. https://doi.org/10.1096/fj.201901117RR

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hou T, Zhang R, Jian C et al (2019) NDUFAB1 confers cardio-protection by enhancing mitochondrial bioenergetics through coordination of respiratory complex and supercomplex assembly. Cell Res 29:754–766. https://doi.org/10.1038/s41422-019-0208-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Chakraborty B, Bhakta S, Sengupta J (2016) Mechanistic insight into the reactivation of BCAII enzyme from denatured and molten globule states by eukaryotic ribosomes and domain V rRNAs. PLoS One 11:e0153928. https://doi.org/10.1371/journal.pone.0153928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Branco AT, Lemos B (2014) High intake of dietary sugar enhances bisphenol A (BPA) disruption and reveals ribosome-mediated pathways of toxicity. Genetics 197:147–157. https://doi.org/10.1534/genetics.114.163170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Shen X, Yin L, Pan X et al (2020) Porcine epidemic diarrhea virus infection blocks cell cycle and induces apoptosis in pig intestinal epithelial cells. Microb Pathog 147:104378. https://doi.org/10.1016/j.micpath.2020.104378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Huang G, Li H, Zhang H (2020) Abnormal expression of mitochondrial ribosomal proteins and their encoding genes with cell apoptosis and diseases. IJMS 21:8879. https://doi.org/10.3390/ijms21228879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Guan X, Zhang H, Qin H et al (2020) CRISPR/Cas9-mediated whole genomic wide knockout screening identifies mitochondrial ribosomal proteins involving in oxygen-glucose deprivation/reperfusion resistance. J Cell Mol Med 24:9313–9322. https://doi.org/10.1111/jcmm.15580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Zhou Q, Hou Z, Zuo S et al (2019) LUCAT1 promotes colorectal cancer tumorigenesis by targeting the ribosomal protein L40- MDM 2-p53 pathway through binding with UBA 52. Cancer Sci 110:1194–1207. https://doi.org/10.1111/cas.13951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Carracedo S, Briand-Amirat L, Dordas-Perpinyà M et al (2022) ProAKAP4 protein marker: towards a functional approach to male fertility. Anim Reprod Sci 247:107074. https://doi.org/10.1016/j.anireprosci.2022.107074

    Article  CAS  PubMed  Google Scholar 

  51. Fang X, Huang L-L, Xu J et al (2019) Proteomics and single-cell RNA analysis of Akap4-knockout mice model confirm indispensable role of Akap4 in spermatogenesis. Dev Biol 454:118–127. https://doi.org/10.1016/j.ydbio.2019.06.017

    Article  CAS  PubMed  Google Scholar 

  52. Zhao W, Li Z, Ping P et al (2018) Outer dense fibers stabilize the axoneme to maintain sperm motility. J Cell Mol Med 22:1755–1768. https://doi.org/10.1111/jcmm.13457

    Article  CAS  PubMed  Google Scholar 

  53. Hoyer-Fender S (2022) Development of the connecting piece in ODF1-deficient mouse spermatids. IJMS 23:10280. https://doi.org/10.3390/ijms231810280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Sarkar S, Yadav S, Mehta P et al (2022) Histone methylation regulates gene expression in the round spermatids to set the RNA payloads of sperm. Reprod Sci 29:857–882. https://doi.org/10.1007/s43032-021-00837-3

    Article  CAS  PubMed  Google Scholar 

  55. Paclik D, Danese S, Berndt U et al (2008) Galectin-4 controls intestinal inflammation by selective regulation of peripheral and mucosal T cell apoptosis and cell cycle. PLoS One 3:e2629. https://doi.org/10.1371/journal.pone.0002629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Cao Z-Q, Guo X-L (2016) The role of galectin-4 in physiology and diseases. Protein Cell 7:314–324. https://doi.org/10.1007/s13238-016-0262-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

We thank the Guangxi Natural Science Foundation Project (2020GXNSFAA297257), Guangxi Science and Technology Program Project (21-220-22), Guangxi University Young and Middle-aged Teachers’ Basic Ability Improvement Project (2020KY13017), Guangxi Zhuang Autonomous Region Administration of Traditional Chinese Medicine Self-financing Scientific Research Project (GZZC2020248), and Guangxi Zhuang Autonomous Region Health and Health Commission Self-financing Scientific Research Course (Z20201416).

Author information

Author notes

  1. Huixin Peng, Yanxin Huang and Guangji Wei contributed equally to this work.

Authors and Affiliations

  1. The Affiliated Hospital of You jiang Medical University for Nationalities, Baise, 533000, Guangxi, China

    Huixin Peng, Yanxin Huang, Guangji Wei, Yanfang Pang, Huixiong Yuan & Wencheng Chen

  2. Graduate School of You jiang Medical University for Nationalities, Baise, 533000, Guangxi, China

    Huixin Peng, Yanxin Huang, Guangji Wei, Yanfang Pang, Huixiong Yuan & Wencheng Chen

  3. Guangxi Key Laboratory of reproductive health and birth defect prevention, Nanning, 530000, Guangxi, China

    Xiong Zou & Yu’an Xie

Authors
  1. Huixin Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yanxin Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guangji Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yanfang Pang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Huixiong Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiong Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yu’an Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Wencheng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Huixin Peng, Yanxin Huang, and Guangji Wei were responsible for experiment operation and paper writing; Yanfang Pang and Huixiong Yuan were responsible for animal feeding and modeling; Xiong Zou was responsible for partial data analysis; Wencheng Chen and Yu’an Xie were responsible for experiment design, paper writing guidance, overall framework construction, and project fund preparation.

Corresponding authors

Correspondence to Yu’an Xie or Wencheng Chen.

Ethics declarations

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Peng, H., Huang, Y., Wei, G. et al. Testicular Toxicity in Rats Exposed to AlCl3: a Proteomics Study. Biol Trace Elem Res 202, 1084–1102 (2024). https://doi.org/10.1007/s12011-023-03745-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-023-03745-6

Keywords

Search

Navigation