Abstract
Phthalate acid esters (PAEs) and their metabolites, such as di-n-butyl phthalate (DBP) and mono-n-butyl phthalate (MBP), are known to cause male reproductive damage. Lactiplantibacillus plantarum RS20D has demonstrated the ability to remove both DBP and MBP in vitro, suggesting its potential as a detoxifying agent against these compounds. This study aimed to investigate the protective effects of RS20D on DBP or MBP-induced male reproductive toxicity in adolescent rats. Oral administration of RS20D significantly mitigated the histological damage to the testes caused by MBP or DBP, restored sperm concentration, morphological abnormalities, and the proliferation index in MBP-exposed rats, and partially reversed spermatogenic damage in DBP-exposed rats. Furthermore, RS20D restored serum levels of estradiol (E2) and testosterone, and superoxide dismutase (SOD) activity in DBP-exposed rats, significantly increased testosterone levels in MBP-exposed rats, and restored copper (Cu) concentrations in the testes after exposure to DBP or MBP. Additionally, RS20D effectively modulated the intestinal microbiota in DBP-exposed rats and partially ameliorated dysbiosis induced by MBP, which may be associated with the alleviation of reproductive toxic effects induced by DBP or MBP. In conclusion, this study demonstrates that RS20D administration can alleviate male reproductive toxicity and gut dysbacteriosis induced by DBP or MBP exposure, providing a dietary strategy for the bioremediation of PAEs and their metabolites.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
References
Das MT, Kumar SS, Ghosh P, Shah G, Malyan SK, Bajar S, Thakur IS, Singh L (2021) Remediation strategies for mitigation of phthalate pollution: challenges and future perspectives. J Hazard Mater 409:124496
Cao XL (2010) Phthalate esters in foods: sources, occurrence, and analytical methods. Compr Rev Food Sci Food Saf 9:21–43
Radke EG, Braun JM, Meeker JD, Cooper GS (2018) Phthalate exposure and male reproductive outcomes: a systematic review of the human epidemiological evidence. Environ Int 121:764–793
Frederiksen H, Skakkebaek NE, Andersson AM (2007) Metabolism of phthalates in humans. Mol Nutr Food Res 51:899–911
Saadeldin IM, Hussein MA, Suleiman AH, Abohassan MG, Ahmed MM, Moustafa AA, Moumen AF, Abdel-Aziz SA (2018) Ameliorative effect of ginseng extract on phthalate and bisphenol A reprotoxicity during pregnancy in rats. Environ Sci Pollut R 25:21205–21215
Zhang Y, Shi G, Cai J, Yang J, Zheng Y, Yu D, Liu Q, Gong Y, Zhang Z (2019) Taxifolin alleviates apoptotic injury induced by DEHP exposure through cytochrome P450 homeostasis in chicken cardiomyocytes. Ecotox Environ Safe 183:109582
Zhang L-D, Li H-C, Chong T, Gao M, Yin J, Fu D-L, Deng Q, Wang Z-M (2014) Prepubertal exposure to genistein alleviates di-(2-ethylhexyl) phthalate induced testicular oxidative stress in adult rats. BioMed Res Int 2014:598630
Zhang L, Gao M, Zhang T, Chong T, Wang Z, Zhai X, Wu Z, Li H (2017) Protective effects of genistein against mono-(2-ethylhexyl) phthalate-induced oxidative damage in prepubertal Sertoli cells. BioMed Res Int 2017:2032697
Rajesh P, Sathish S, Srinivasan C, Selvaraj J, Balasubramanian K (2013) Diethyl Hexyl Phthalate (DEHP) is associated with insulin resistance in adipose tissue of male rat: protective role of antioxidant vitamins (C & E). J Cell Biochem 114:558–569
Abdel-Kawi SH, Hashem KS, Abd-Allah S (2016) Mechanism of diethylhexylphthalate (DEHP) induced testicular damage and of grape seed extract-induced protection in the rat. Food Chem Toxicol 90:64–75
Oishi S (1986) Testicular atrophy induced by di (2-ethylhexyl) phthalate: changes in histology, cell specific enzyme activities and zinc concentrations in rat testis. Arch Toxicol 59:290–295
Oishi S, Hiraga K (1983) Testicular atrophy induced by di-2-ethylhexyl phthalate: effect of zinc supplement. Toxicol Appl Pharm 70:43–48
Zhang S, Liu R, Ma Y, Ma Y, Feng H, Ding X, Zhang Q, Li Y, Shan J, Bian H, Zhu R, Meng Q (2024) Lactiplantibacillus plantarum ATCC8014 alleviates postmenopausal hypercholesterolemia in mice by remodeling intestinal microbiota to increase secondary bile acid excretion. J Agri Food Chem 72:6236–6249
Hatab S, Yue T, Mohamad O (2012) Reduction of patulin in aqueous solution by lactic acid bacteria. J Food Sci 77:M238–M241
Lai J, Zhu Y, Liao X, Zhang M, Li J, Li Q, Liu A, He L, Liu S (2022) Cell components, interaction types and functional groups involved in the in vitro binding of bisphenol A by Lactiplantibacillus plantarum RS20D and DL7X. J Appl Microbiol 132:2968–2979
Trinder M, McDowell T, Daisley B, Ali S, Leong H, Sumarah M, Reid G (2016) Probiotic Lactobacillus rhamnosus reduces organophosphate pesticide absorption and toxicity to Drosophila melanogaster. Appl Environ Microb 82:6204–6213
Zhai Q, Yin R, Yu L, Wang G, Tian F, Yu R, Zhao J, Liu X, Chen YQ, Zhang H (2015) Screening of lactic acid bacteria with potential protective effects against cadmium toxicity. Food Control 54:23–30
Zhao L, Li X, Yang Q, Zhuang D, Pan X, Li L (2020) Adsorption kinetics and mechanism of di-n-butyl phthalate by Leuconostoc mesenteroides. Food Sci Nutr 8:6153–6163
Zhao L, Pan X, Yang Q, Zhao R, Li X (2021) The ability of lactic acid bacteria strains to remove di-n-butyl phthalate in simulated food matrices. Int J Food Sci Tech 56:553–562
Tian X, Yu Z, Feng P, Ye Z, Li R, Liu J, Hu J, Kakade A, Liu P, Li X (2019) Lactobacillus plantarum TW1-1 alleviates diethylhexylphthalate-induced testicular damage in mice by modulating gut microbiota and decreasing inflammation. Front Cell Infect Microbiol 9:221
Shi X, Hu C, Cai S, Tao X, Zhou Y, Smidt H, Ye B (2020) Protective effects of Lactobacillus plantarum strain P1 against toxicity of the environmental oestrogen di-n-butyl phthalate in rats. Benef Microbes 11:803–813
Baralić K, Živančević K, Javorac D, Djordjevic AB, Anđelković M, Jorgovanović D, Miljaković EA, Ćurčić M, Bulat Z, Antonijević B (2020) Multi-strain probiotic ameliorated toxic effects of phthalates and bisphenol A mixture in Wistar rats. Food Chem Toxicol 143:111540
Zhu Y-T, Lai J-H, Liao X-D, Liu S-L (2018) Screening of lactic acid bacteria strains for their ability to bind phthalate monoesters in vitro and the binding characteristics. Food Control 90:364–371
Abdel-Maksoud FM, Ali FAZ, Akingbemi BTJRT (2019) Prenatal exposures to bisphenol A and di (2-ethylhexyl) phthalate disrupted seminiferous tubular development in growing male rats. Reprod Toxicol 88:85–90
Chen X, An H, Ao L, Sun L, Liu W, Zhou Z, Wang Y, Cao J (2011) The combined toxicity of dibutyl phthalate and benzo (a) pyrene on the reproductive system of male Sprague Dawley rats in vivo. J Hazard Mater 186:835–841
Qi J, Gao X, Zhong X, Zhang N, Wang R, Zhang H, Pan T, Liu X, Yao Y, Wu Q (2019) Selective inhibition of Aurora A and B kinases effectively induces cell cycle arrest in t (8; 21) acute myeloid leukemia. Biomed Pharmacother 117:109113
Martino-Andrade AJ, Chahoud I (2010) Reproductive toxicity of phthalate esters. Mol Nutr Food Res 54:148–157
Johnson KJ, Heger NE, Boekelheide K (2012) Of mice and men (and rats): phthalate-induced fetal testis endocrine disruption is species-dependent. Toxicol Sci 129:235–248
Foster PM, Thomas LV, Cook MW, Gangolli SD (1980) Study of the testicular effects and changes in zinc excretion produced by some n-alkyl phthalates in the rat. Toxicol Appl Pharm 54:392–398
Asadi N, Bahmani M, Kheradmand A, Rafieian-Kopaei M (2017) The impact of oxidative stress on testicular function and the role of antioxidants in improving it: a review. J Clin Diagn Res 11:IE01–IE05
Claus SP, Guillou H, Ellero-Simatos S (2016) The gut microbiota: a major player in the toxicity of environmental pollutants? Npj Biofilms Microbi 2:1–11
Zhang T, Zhou X, Zhang X, Ren X, Wu J, Wang Z, Wang S, Wang Z (2022) Gut microbiota may contribute to the postnatal male reproductive abnormalities induced by prenatal dibutyl phthalate exposure. Chemosphere 287:132046
Lei M, Menon R, Manteiga S, Alden N, Hunt C, Alaniz RC, Lee K, Jayaraman A (2019) Environmental chemical diethylhexyl phthalate alters intestinal microbiota community structure and metabolite profile in mice. Msystems 4:e00724–e819
Fu X, Han H, Li Y, Xu B, Dai W, Zhang Y, Zhou F, Ma H, Pei X (2021) Di-(2-ethylhexyl) phthalate exposure induces female reproductive toxicity and alters the intestinal microbiota community structure and fecal metabolite profile in mice. Environ Toxicol 36(6):1226–1242
Wang G, Chen Q, Tian P, Wang L, Li X, Lee Y, Zhao J, Zhang H, Chen W (2020) Gut microbiota dysbiosis might be responsible to different toxicity caused by Di-(2-ethylhexyl) phthalate exposure in murine rodents. Environ Pollut 261:114164
Zhao T, Wei Y, Wang J, Han L, Sun M, Wu Y, Shen L, Long C, Wu S, Wei G (2020) The gut-microbiota-testis axis mediated by the activation of the Nrf2 antioxidant pathway is related to prepuberal steroidogenesis disorders induced by di-(2-ethylhexyl) phthalate. Environ Pollut R 27:35261–35271
Acknowledgements
This work was supported by the National Natural Science Foundation of China (Grant No. 31871770) and the Science & Technology Foundation of Sichuan Province, China (Grant No. 2020YFN0133).
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The National Natural Science Foundation of China.
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Zhu Yuan-ting: Investigation, Methodology, Writing-original draft; Wang Xing-jie: Investigation, Methodology; Liu Shu-liang: Funding Acquisition, Supervision, Conceptualization; Lai Jing-hui: Formal Analysis, Data curation; Li Jian-long: Resources; Hu Kai-di: Data curation, Visualization; Liu Ai-ping: Formal Analysis; Yang Yong: Project administration; Resources; He Li: Writing-review & editing; Chen Shu-juan: Writing-revie w& editing; Ao Xiao-lin: Writing-review & editing; Zou Li-kou: Project administration, Resources.
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Zhu, Yt., Wang, Xj., Liu, Sl. et al. Lactiplantibacillus plantarum RS20D Alleviates Male Reproductive Toxicity Induced by Pubertal Exposure to Di-n-butyl Phthalate and Mono-n-butyl Phthalate. Probiotics & Antimicro. Prot. (2024). https://doi.org/10.1007/s12602-024-10276-6
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DOI: https://doi.org/10.1007/s12602-024-10276-6