Skip to main content
Log in

Tannic acid alleviates 3-nitropropionic acid-induced ovarian damage in Brandt’s vole (Lasiopodomys brandtii)

  • Reproductive Endocrinology: Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Tannic acid (TA) is a polyphenol with antioxidant properties present in various plants. In this study, we explored the protective effect of TA against ovarian oxidative stress in Brandt’s voles and its underlying mechanism. At various doses, 3-nitropropionic acid (3-NPA) was intraperitoneally injected into Brandt’s voles to simulate ovarian oxidative stress. Thereafter, various doses of TA were intragastrically administered to examine the protective effect of TA against 3-NPA-induced ovarian damage. Changes in inflammation, autophagy, apoptosis, and oxidative stress-related factors were investigated through various biochemical and histological techniques. Ovarian oxidative stress was successfully induced by the intraperitoneal administration of 12.5 mg/kg 3-NPA for 18 days. As a result, the ovarian coefficient decreased and ovarian tissue fibrosis was induced. TA treatment effectively alleviated the increase in luteinizing hormone and follicle-stimulating hormone levels; the decrease in estradiol, progesterone, and anti-Müllerian hormone levels; and the decline in fertility induced by 3-NPA. Compared to that in the 3-NPA group, TA decreased the expression of autophagy-related proteins beclin-1 and LC3, as well as the level of apoptosis. It also activated the AKT/mTOR signaling pathway, downregulated PTEN and p-NF-κB expression, and upregulated Nrf2 expression. In conclusion, our findings indicate that TA could inhibit autophagy via the regulation of AKT/mTOR signaling, suppressing oxidative damage and inflammatory responses through Nrf2 to alleviate 3-NPA-induced ovarian damage. Collectively, the current findings highlight the protective effects of TA in Brandt’s vole, where it promotes the maintenance of normal ovarian function.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data availability

The data will be made available upon request.

References

  1. Guo L, Liu XC, Chen H, Wang WG, Gu C, Li B. Decrease in ovarian reserve through the inhibition of SIRT1-mediated oxidative phosphorylation. Aging. 2022;14:2335–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kükürt A, Karapehlivan M. Protective effect of astaxanthin on experimental ovarian damage in rats. J Biochem Mol Toxicol. 2022;36:e22966.

    Article  PubMed  Google Scholar 

  3. Patel S, Zhou C, Rattan S, Flaws JA. Effects of endocrine-disrupting chemicals on the ovary. Biol Reprod. 2015;93:20.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kandaraki E, Chatzigeorgiou A, Livadas S, Palioura E, Economou F, Koutsilieris M, Palimeri S, Panidis D, Diamanti-Kandarakis E. Endocrine disruptors and polycystic ovary syndrome (PCOS): elevated serum levels of bisphenol A in women with PCOS. J Clin Endocrinol Metab. 2011;96:E480–4.

    Article  CAS  PubMed  Google Scholar 

  5. Behrman HR, Kodaman PH, Preston SL, Gao S. Oxidative stress and the ovary. J Soc Gynecol Investig. 2001;8:S40–2.

    CAS  PubMed  Google Scholar 

  6. Zuo T, Zhu M, Xu W. Roles of oxidative stress in polycystic ovary syndrome and cancers. Oxidative Med Cell Longev. 2016;2016:8589318.

    Article  Google Scholar 

  7. Mirzaei M, Razi M, Sadrkhanlou R. Nanosilver particles increase follicular atresia: correlation with oxidative stress and aromatization. Environ Toxicol. 2017;32:2244–55.

    Article  CAS  PubMed  Google Scholar 

  8. Wilcox CS. Effects of tempol and redox-cycling nitroxides in models of oxidative stress. Pharmacol Ther. 2010;126:119–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Li W, Dong Y, Dong Q, Sun H, Zhang Y, Wang Z. The remarkable hypoxia tolerance in Brandt’s voles (Lasiopodomys brandtii). Eur J Neurosci. 2021;53:1652–60.

    Article  CAS  PubMed  Google Scholar 

  10. Shi L, Chen B, Wang X, Huang M, Qiao C, Wang J, Wang Z. Antioxidant response to severe hypoxia in Brandt’s vole Lasiopodomys brandtii. Integr Zool. 2022;17:581–95.

    Article  CAS  PubMed  Google Scholar 

  11. Hussain T, Tan B, Yin Y, Blachier F, Tossou MC, Rahu N. Oxidative stress and inflammation: what polyphenols can do for us? Oxidative Med Cell Longev. 2016;2016:7432797.

    Article  Google Scholar 

  12. Ramirez-Ramirez V, Macias-Islas MA, Ortiz GG, Pacheco-Moises F, Torres-Sanchez ED, Sorto-Gomez TE, Cruz-Ramos JA, Orozco-Aviña G, Celis De La Rosa AJ. Efficacy of fish oil on serum of TNFα, IL-1β, and IL-6 oxidative stress markers in multiple sclerosis treated with interferon beta-1b. Oxidative Med Cell Longev. 2013;2013:709493.

    Article  CAS  Google Scholar 

  13. Singh AK, Vinayak M. Curcumin attenuates CFA induced thermal hyperalgesia by modulation of antioxidant enzymes and down regulation of TNF-α, IL-1β and IL-6. Neurochem Res. 2015;40:463–72.

    Article  CAS  PubMed  Google Scholar 

  14. Sadeghi A, Rostamirad A, Seyyedebrahimi S, Meshkani R. Curcumin ameliorates palmitate-induced inflammation in skeletal muscle cells by regulating JNK/NF-kB pathway and ROS production. Inflammopharmacology. 2018;26:1265–72.

    Article  CAS  PubMed  Google Scholar 

  15. Oliviero F, Scanu A, Zamudio-Cuevas Y, Punzi L, Spinella P. Anti-inflammatory effects of polyphenols in arthritis. J Sci Food Agric. 2018;98:1653–9.

    Article  CAS  PubMed  Google Scholar 

  16. Figueroa-Espinoza MC, Zafimahova A, Alvarado PG, Dubreucq E, Poncet-Legrand C. Grape seed and apple tannins: emulsifying and antioxidant properties. Food Chem. 2015;178:38–44.

    Article  CAS  PubMed  Google Scholar 

  17. Dai X, Zhou L-Y, Xu T-T, Wang Q-Y, Luo B, Li Y-Y, Gu C, Li S-P, Wang A-Q, Wei W-H, Yang S. Reproductive responses of the male Brandt’s vole, Lasiopodomys brandtii (Rodentia: Cricetidae) to tannic acid. Zoologia. 2020;37:1–11.

    Article  Google Scholar 

  18. Ye MH, Nan YL, Ding MM, Hu JB, Liu Q, Wei WH, Yang SM. Effects of dietary tannic acid on the growth, hepatic gene expression, and antioxidant enzyme activity in Brandt’s voles (Microtus brandti). Comp Biochem Physiol B Biochem Mol Biol. 2016;196-197:19–26.

    Article  CAS  PubMed  Google Scholar 

  19. Li B, Weng Q, Liu Z, Shen M, Zhang J, Wu W, Liu H. Selection of antioxidants against ovarian oxidative stress in mouse model. J Biochem Mol Toxicol. 2017;31:e21997.

    Article  Google Scholar 

  20. Khashchenko E, Vysokikh M, Uvarova E, Krechetova L, Vtorushina V, Ivanets T, Volodina M, Tarasova N, Sukhanova I, Sukhikh G. Activation of systemic inflammation and oxidative stress in adolescent girls with polycystic ovary syndrome in combination with metabolic disorders and excessive body weight. J Clin Med. 2020;9:1399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mancini A, Bruno C, Vergani E, d’Abate C, Giacchi E, Silvestrini A. Oxidative stress and low-grade inflammation in polycystic ovary syndrome: controversies and new insights. Int J Mol Sci. 2021;22:1667.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Behl T, Rana T, Alotaibi GH, Shamsuzzaman M, Naqvi M, Sehgal A, Singh S, Sharma N, Almoshari Y, Abdellatif AAH, Iqbal MS, Bhatia S, Al-Harrasi A, Bungau S. Polyphenols inhibiting MAPK signalling pathway mediated oxidative stress and inflammation in depression. Biomed Pharmacother. 2022;146:112545.

    Article  CAS  PubMed  Google Scholar 

  23. Boccellino M, D’Angelo S. Anti-obesity effects of polyphenol intake: current status and future possibilities. Int J Mol Sci. 2020;21:5642.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Davinelli S, De Stefani D, De Vivo I, Scapagnini G. Polyphenols as caloric restriction mimetics regulating mitochondrial biogenesis and mitophagy. Trends Endocrinol Metab. 2020;31:536–50.

    Article  CAS  PubMed  Google Scholar 

  25. La Marca A, Sighinolfi G, Radi D, Argento C, Baraldi E, Artenisio AC, Stabile G, Volpe A. Anti-Müllerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update. 2010;16:113–30.

    Article  PubMed  Google Scholar 

  26. Niermann S, Rattan S, Brehm E, Flaws JA. Prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP) affects reproductive outcomes in female mice. Reprod Toxicol. 2015;53:23–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Uzumcu M, Zachow R. Developmental exposure to environmental endocrine disruptors: consequences within the ovary and on female reproductive function. Reprod Toxicol. 2007;23:337–52.

    Article  CAS  PubMed  Google Scholar 

  28. An R, Wang XF, Yang L, Zhang JJ, Wang NN, Xu FB, Hou Y, Zhang HQ, Zhang LS. Polystyrene microplastics cause granulosa cells apoptosis and fibrosis in ovary through oxidative stress in rats. Toxicology. 2021;449:152665.

    Article  CAS  PubMed  Google Scholar 

  29. Briley SM, Jasti S, McCracken JM, Hornick JE, Fegley B, Pritchard MT, Duncan FE. Reproductive age-associated fibrosis in the stroma of the mammalian ovary. Reproduction. 2016;152:245–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Surh YJ, Na HK. NF-κB and Nrf2 as prime molecular targets for chemoprevention and cytoprotection with anti-inflammatory and antioxidant phytochemicals. Genes Nutr. 2008;2:313–7.

    Article  CAS  PubMed  Google Scholar 

  31. Wardyn JD, Ponsford AH, Sanderson CM. Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways. Biochem Soc Trans. 2015;43:621–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Xie YL, Chu JG, Jian XM, Dong JZ, Wang LP, Li GX, Yang NB. Curcumin attenuates lipopolysaccharide/d-galactosamine-induced acute liver injury by activating Nrf2 nuclear translocation and inhibiting NF-kB activation. Biomed Pharmacother. 2017;91:70–7.

    Article  CAS  PubMed  Google Scholar 

  33. Hennig P, Garstkiewicz M, Grossi S, Di Filippo M, French LE, Beer HD. The crosstalk between Nrf2 and Inflammasomes. Int J Mol Sci. 2018;19:562.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ma Q. Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol. 2013;53:401–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zusso M, Lunardi V, Franceschini D, Pagetta A, Lo R, Stifani S, Frigo AC, Giusti P, Moro S. Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR4/NF-kB pathway. J Neuroinflammation. 2019;16:148.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Shen M, Lin F, Zhang J, Tang Y, Chen WK, Liu H. Involvement of the up-regulated FoxO1 expression in follicular granulosa cell apoptosis induced by oxidative stress. J Biol Chem. 2012;287:25727–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zhou J, Peng X, Mei S. Autophagy in ovarian follicular development and atresia. Int J Biol Sci. 2019;15:726–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Chen Q, Xu Z, Li X, Du D, Wu T, Zhou S, Yan W, Wu M, Jin Y, Zhang J, Wang S. Epigallocatechin gallate and theaflavins independently alleviate cyclophosphamide-induced ovarian damage by inhibiting the overactivation of primordial follicles and follicular atresia. Phytomedicine. 2021;92:153752.

    Article  CAS  PubMed  Google Scholar 

  39. Luo LL, Huang J, Fu YC, Xu JJ, Qian YS. Effects of tea polyphenols on ovarian development in rats. J Endocrinol Investig. 2008;31:1110–8.

    Article  CAS  Google Scholar 

  40. Caramés B, Taniguchi N, Otsuki S, Blanco FJ, Lotz M. Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with cell death and osteoarthritis. Arthritis Rheum. 2010;62:791–801.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Valente G, Morani F, Nicotra G, Fusco N, Peracchio C, Titone R, Alabiso O, Arisio R, Katsaros D, Benedetto C, Isidoro C. Expression and clinical significance of the autophagy proteins BECLIN 1 and LC3 in ovarian cancer. Biomed Res Int. 2014;2014:462658.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kumariya S, Ubba V, Jha RK, Gayen JR. Autophagy in ovary and polycystic ovary syndrome: role, dispute and future perspective. Autophagy. 2021;17:2706–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Chang L, Graham PH, Hao J, Ni J, Bucci J, Cozzi PJ, Kearsley JH, Li Y. PI3K/Akt/mTOR pathway inhibitors enhance radiosensitivity in radioresistant prostate cancer cells through inducing apoptosis, reducing autophagy, suppressing NHEJ and HR repair pathways. Cell Death Dis. 2014;5:e1437.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Xue JF, Shi ZM, Zou J, Li XL. Inhibition of PI3K/AKT/mTOR signaling pathway promotes autophagy of articular chondrocytes and attenuates inflammatory response in rats with osteoarthritis. Biomed Pharmacother. 2017;89:1252–61.

    Article  CAS  PubMed  Google Scholar 

  45. Sahu R, Dua TK, Das S, De Feo V, Dewanjee S. Wheat phenolics suppress doxorubicin-induced cardiotoxicity via inhibition of oxidative stress, MAP kinase activation, NF-κB pathway, PI3K/Akt/mTOR impairment, and cardiac apoptosis. Food Chem Toxicol. 2019;125:503–19.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China [grant number: 31971418] and the Priority Academic Program Development of Jiangsu Higher Education Institutions.

Author information

Authors and Affiliations

Authors

Contributions

Ming-Hao Yu designed and performed the experiments and analyzed the data; Rui-Yang Fan, Dao-Chen Wang and Yu-Xuan Han designed the experiments and collected the data. Xin Dai and Sheng-Mei Yang revised and edited the manuscript. All authors read and accepted the manuscript.

Corresponding authors

Correspondence to Minghao Yu or Sheng-Mei Yang.

Ethics declarations

IRB approval

All procedures performed in the studies involving animals were approved by the Animal Care and Use Committee of Yangzhou University (No. SJXY-2).

Ethical statement

All applicable international, national, and/or institutional guidelines for animal care and use were adhered to.

Conflict of interest

The authors declare no conflict of interest.

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

Yu, M., Fan, R., Wang, D. et al. Tannic acid alleviates 3-nitropropionic acid-induced ovarian damage in Brandt’s vole (Lasiopodomys brandtii). Reprod. Sci. (2024). https://doi.org/10.1007/s43032-024-01543-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s43032-024-01543-6

Keywords

Navigation