L-Epicatechin Partially Alleviates Ochratoxin A–Induced Oxidative and Endoplasmic Reticulum Stress and Improves Developmental Competence of Porcine Embryos During In Vitro Culture

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium species, frequently detected in contaminated food and animal feed [1]. Despite advancements in food safety measures, OTA contamination remains a persistent issue in livestock production systems [2]. Exposure to OTA poses significant health threats, including nephrotoxicity, immunotoxicity, and teratogenicity [3]. At the molecular level, OTA induces oxidative stress primarily through the activation of mitochondrial NADPH–cytochrome P450 reductase, resulting in excessive production of reactive oxygen species (ROS), cellular injury, and apoptosis. Additionally, OTA disrupts protein homeostasis, leading to endoplasmic reticulum (ER) stress and subsequent activation of the unfolded protein response (UPR) [4], [5], [6]. It also impairs mitochondrial oxidative phosphorylation and inhibits key enzymes required for protein synthesis [7]. Recent research has further demonstrated the reproductive toxicity of OTA, including its embryotoxic effects across various species [8], [9], [10]. In porcine embryos, OTA predominantly induces oxidative stress–mediated apoptosis, which may secondarily trigger ER stress through the PERK/NRF2 signaling pathway, ultimately compromising embryonic development [11], [12].

In swine reproduction, in vitro production (IVP) of embryos is a widely employed biotechnology for genetic improvement and reproductive management [13], [14]. However, the efficiency of porcine IVP is often hindered by oxidative stress and ER stress, both of which impair embryonic development, reduce blastocyst formation rates, and compromise overall embryo quality [15], [16], [17]. To overcome these limitations, a range of antioxidants—including plant-derived polyphenols—have been investigated for their ability to reduce oxidative damage and enhance embryo viability during in vitro culture [18], [19], [20].

L-Epicatechin (L-E, 2-(2,5-dihydroxyphenyl)-chroman-3,5,7-triol), a small molecule based on a chroman skeleton [21], is naturally found in a wide range of plants and traditional medicinal herbs [22], [23], [24]. Its chemical structure features hydroxyl groups at the 2 and 5 positions of the aromatic ring and at the 3, 5, and 7 positions of the chroman ring. These structural elements are believed to underlie its potent antioxidant activity. Specifically, the hydroxyl groups at positions 2 and 5 are thought to be highly reactive, contributing to free radical stabilization, while those on the chroman ring further enhance its antioxidative capacity [25]. Additionally, the conjugated system between the aromatic ring and chroman nucleus may facilitate electron delocalization, thereby improving the molecule’s radical-scavenging stability [26], [27]. Although the antioxidant properties of L-E have been well documented [22], [24], [28], [29], its role in supporting embryonic development or mitigating stress-induced damage during in vitro embryo culture in livestock remains largely unexplored.

This study aimed to investigate whether L-E, a natural flavonoid with known antioxidant properties, could mitigate the adverse effects of OTA-induced oxidative and ER stress during porcine embryo in vitro culture. We evaluated embryonic development, oxidative stress, mitochondrial and ER function, and apoptosis to elucidate the protective mechanisms of L-E. This research provides novel insights into the application of L-E for enhancing in vitro embryo development and may contribute to the optimization of IVP protocols in swine breeding programs.

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