Fisetin alleviates oxidative stress and promotes porcine early embryonic development via activation of the NRF2-ARE signalling pathway

Wei, Huakai; Qi, Jiajia; Wang, Yanqiu; Qu, Hexuan; Yan, Chenxuan; Li, Tiantian; Wang, Yu; Sun, Hao; Sun, Boxing; Liang, Shuang

doi:.0.0.0

Article

https://doi.org/10.5713/ab.24.0691 [Accepted] Published online February 27, 2025.

Fisetin alleviates oxidative stress and promotes porcine early embryonic development via activation of the NRF2-ARE signalling pathway

Huakai Wei¹

, Boxing Sun^1,*

, Shuang Liang^1,*

Department of Animals Sciences, College of Animal Sciences, Jilin University, Chuangchun, China

Correspondence: Boxing Sun,Email: Sunpathing@vip.163.com
Shuang Liang, Tel: +86-18946566823, Fax: +86-431-87836550, Email: liangshuang85@jlu.edu.cn

Received: 5 October 2024 • Revised: 5 November 2024 • Accepted: 19 December 2024

Abstract

Objective
We improved the developmental capacity of porcine early embryos via supplementation with fisetin during in vitro culture (IVC). In addition, we investigated the antioxidant mechanism of fisetin via activation of the NRF2-ARE signalling pathway in porcine early embryos.
Methods
Fisetin (0, 1, 2.5 and 5 μM) was supplemented during IVC to observe its effects on the developmental ability of porcine parthenogenetic activation (PA), in vitro fertilization (IVF) and somatic cell nuclear transfer (SCNT) embryos. The effects of fisetin supplementation on the antioxidant capacity, mitochondrial function, cell proliferation and apoptosis levels of porcine PA embryos were detected via fluorescence staining, and the expression levels of genes related to apoptosis, pluripotency and the NRF2 pathway were also examined.
Results
Compared with the control, 1 μM fisetin during IVC increased the developmental ability of porcine PA, IVF and SCNT embryos. Additionally, fisetin significantly decreased reactive oxygen species (ROS) and apoptosis levels; increased pluripotency during embryonic development, cell proliferation and glutathione (GSH) levels; and improved mitochondrial function in PA embryos. Moreover, the levels of Kelch-like ECH-associated protein 1 (KEAP1) significantly decreased, and the levels of NFE2-like bZIP transcription factor 2 (NRF2) and its downstream antioxidant enzymes significantly increased after fisetin supplementation.
Conclusion
Our data reveal that fisetin protects porcine early embryos from oxidative stress during IVC by activating the NRF2-ARE signalling pathway, thereby improving the success of in vitro embryo production.

Keywords: Fisetin; Porcine early embryos; Oxidative stress; NRF2-ARE