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Resveratrol attenuates doxorubicin-induced toxicity during in vitro culture of mouse-isolated preantral follicles

Published online by Cambridge University Press:  19 September 2024

G.A.L. Silva Open the ORCID record for G.A.L. Silva [Opens in a new window] ,
A.P.O Monte ,
A.T.V. França ,
I.M. Mota ,
J.L. Oliveira Junior ,
K.O. Andrade ,
L.M. Souza ,
R.L.S. Silva ,
V.S. Guimarães  and
R.S. Barberino
...Show all authors
G.A.L. Silva*
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Department of Veterinary Medicine, Federal University of Vale do São Francisco - UNIVASF, Petrolina, Pernambuco, Brazil
A.P.O Monte
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Department of Veterinary Medicine, Federal University of Vale do São Francisco - UNIVASF, Petrolina, Pernambuco, Brazil
A.T.V. França
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Department of Veterinary Medicine, Federal University of Vale do São Francisco - UNIVASF, Petrolina, Pernambuco, Brazil
I.M. Mota
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Department of Veterinary Medicine, Federal University of Vale do São Francisco - UNIVASF, Petrolina, Pernambuco, Brazil
J.L. Oliveira Junior
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Department of Veterinary Medicine, Federal University of Vale do São Francisco - UNIVASF, Petrolina, Pernambuco, Brazil
K.O. Andrade
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Department of Veterinary Medicine, Federal University of Vale do São Francisco - UNIVASF, Petrolina, Pernambuco, Brazil
L.M. Souza
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Department of Veterinary Medicine, Federal University of Vale do São Francisco - UNIVASF, Petrolina, Pernambuco, Brazil
R.L.S. Silva
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Department of Veterinary Medicine, Federal University of Vale do São Francisco - UNIVASF, Petrolina, Pernambuco, Brazil
V.S. Guimarães
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Department of Veterinary Medicine, Federal University of Vale do São Francisco - UNIVASF, Petrolina, Pernambuco, Brazil
R.S. Barberino
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Department of Veterinary Medicine, Federal University of Vale do São Francisco - UNIVASF, Petrolina, Pernambuco, Brazil
R.C. Palheta Junior
Affiliation:
Veterinary Pharmacology Laboratory, Department of Veterinary Medicine, Federal University of Vale do São Francisco - UNIVASF, Petrolina, Pernambuco, Brazil
J.E.J. Smitz
Affiliation:
Follicle Biology Laboratory, Free University Brussels-VUB, Brussels, Belgium
M.H.T. Matos
Affiliation:
Nucleus of Biotechnology Applied to Ovarian Follicle Development, Department of Veterinary Medicine, Federal University of Vale do São Francisco - UNIVASF, Petrolina, Pernambuco, Brazil
*
Corresponding author: Gizele Augusta Lemos da Silva; Email: [email protected]
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Summary

The aims of this study were to evaluate the doxorubicin concentration that induces toxic effects on in vitro culture of isolated mouse secondary follicles and to investigate whether resveratrol can inhibit or reduce this toxicity. Secondary follicles were isolated and cultured for 12 days in control medium (α-MEM+) or in α-MEM+ supplemented with doxorubicin (0.1 µg/ml) or different concentrations of resveratrol (0.5, 2, or 5 µM) associated with doxorubicin (0.1 µg/ml) (experiment 1). For experiment 2, follicles were cultured in α-MEM+ alone or supplemented with doxorubicin (0.3 µg/ml) or different concentrations of resveratrol (5 or 10 µM) associated or not with doxorubicin (0.3 µg/ml) (experiment 2). The endpoints analyzed were morphology (survival), antrum formation, follicular diameter, mitochondrial activity, glutathione (GSH) levels and DNA fragmentation. In the first experiment, doxorubicin (0.1 µg/ml) maintained survival and antrum formation similar to the control, while 5 µM resveratrol showed increased parameters, maintained mitochondrial activity and increased GSH levels compared to the control. In the second experiment, doxorubicin (0.3 µg/ml) reduced survival, antrum formation and follicular diameter compared to the control. Resveratrol at a concentration of 10 µM attenuated the damage caused by doxorubicin by improving follicular survival and did not present DNA fragmentation. In conclusion, supplementation of the in vitro culture medium with 0.3 µg/ml doxorubicin reduced the survival and impaired the development of mouse-isolated preantral follicles. Resveratrol at 10 µM reduced doxorubicin-induced follicular atresia, without DNA fragmentation in the follicles.

Keywords

antioxidantchemotherapyfertility preservationoocyteovary
Type
Research Article
Information
Zygote , Volume 32 , Issue 4 , August 2024 , pp. 294 - 302
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Copyright
© The Author(s), 2024. Published by Cambridge University Press

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