ORIGINAL RESEARCH article
Front. Vet. Sci.
Sec. Animal Reproduction - Theriogenology
Volume 12 - 2025 | doi: 10.3389/fvets.2025.1621738
MNQ Derivative D19 Alleviates LPS-Induced Inflammation and Oxidative Stress in Sheep Follicular Granulosa Cells through the GPX4-Mediated Ferroptosis
Provisionally accepted
Chunlu Chen1Jia Lu1Yuhan Qu1Jianhua Dong1Yihao Hong1Yongping Ren1Shouqing Jiang1Dong Wang2
Luis A.J. Mur3
Lihua Lyu1*- 1Shanxi Agricultural University, Jinzhong, China
- 2Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, Beijing, China
- 3Department of Biology and Health, Aberystwyth University, Wales, SY23 3DA, Wales, United Kingdom
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2-methoxy-1,4-naphthoquinone (MNQ), a compound derived from Impatiens balsamina L., is recognized for its anti-inflammatory and antioxidant properties. However, the effects of D19, a derivative of MNQ, remain unexplored. This study aimed to elucidate the protective effect of D19 against LPS-induced follicular granulosa cells (GCs) dysfunction in sheep and its underlying molecular mechanisms. LPS was used to establish an in vitro model of inflammation and oxidative stress in GCs. D19 treatment then alleviated these LPS-induced effects, including steroid hormone synthesis disorders. Mechanistically, D19 attenuated LPS-induced ferroptosis in GCs by restoring the expression of the key ferroptosis regulator GPX4. Subsequently, interfering with GPX4 activated NF-κB and upregulated the expression of inflammatory factors (TNF-α, IL-1β, IL-6) while disrupting NRF2 and inhibiting the expression of antioxidant-related factors (CAT, GSH-PX, SOD2). D19 effectively protected GCs from GPX4 deficiency-induced inflammation and oxidative damage. Furthermore, D19 mitigated ferroptosis caused by GPX4 deficiency and maintained iron metabolic homeostasis by restoring the morphology of GCs, increasing mitochondrial membrane potential, decreasing the accumulation of Fe 2+ and lipid peroxides, and promoting the expression of GPX4 and FTH1. D19 also improved steroid hormone secretion abnormalities caused by GPX4 deficiency. These results demonstrate that D19 protects sheep follicular GCs from LPS-induced damage by modulating the GPX4-mediated ferroptosis signaling pathway, providing new potential drugs and therapeutic targets for addressing GCs dysfunction and follicular developmental abnormalities.
Keywords: lipopolysaccharide, Granulosa Cells, Inflammation, Oxidative Stress, ferroptosis
Received: 01 May 2025; Accepted: 18 Aug 2025.
Copyright: © 2025 Chen, Lu, Qu, Dong, Hong, Ren, Jiang, Wang, Mur and Lyu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lihua Lyu, Shanxi Agricultural University, Jinzhong, China
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