Dose-dependent effects of ovalbumin-induced allergic asthma on systemic inflammation, oxidative stress and preimplantation embryo viability, and the protective role of tocotrienol-rich fraction supplementation in mice

Allergic asthma is an inflammatory airway disease affecting approximately 339 million people worldwide encompassing both children and adults. Its pathogenesis involves activation of T-helper type 2 (Th2) immune responses and oxidative stress resulting from an imbalance between reactive oxygen species (ROS) and antioxidants. This imbalance further exacerbates airway inflammation and tissue injury. While the respiratory manifestations of asthma are well-characterised, its systemic repercussions on reproductive physiology and early embryonic stage remain poorly understood. Maternal asthma has been associated with adverse pregnancy outcomes including preterm birth and foetal growth restriction likely due to systemic inflammation and oxidative stress during the sensitive preimplantation period. Given that inflammatory and oxidative insults at this stage can disrupt developmental potential, morphological quality, organelles features and epigenetic regulation in embryos, maternal supplementation with natural compounds possessing both antioxidant and anti-inflammatory properties may offer protection. This study aimed to determine the protective effects of maternal tocotrienol-rich fraction supplementation (60 mg/kg body weight) on systemic inflammation and oxidative stress, pregnancy hormone levels and subsequent effects on developmental potential, morphological quality, ultrastructural features and gene expression of 2-cell embryos in a mouse model of OVA-induced allergic asthma. In Experiment I, the study established that increasing doses of ovalbumin (OVA; 50–150 µg/200 µL) elicited dose-dependent maternal inflammation and oxidative stress significantly impairing 2-cell embryo development and morphology. In Experiment II, maternal supplementation with tocotrienol-rich fraction (TRF; 60 mg/kg body weight) markedly ameliorated systemic inflammation and oxidative stress markers, and enhanced the developmental potential and morphological quality of two-cell embryos. In addition, transmission electron microscopy (TEM) revealed increased organelles and mitochondrial volumes, mitochondrial clustering and enhanced mitochondria-lipid droplets interaction resulted in peridroplet mitochondria formation suggesting improved inter-organelle communication. Moreover, gene expression profiling (Fluidigm qPCR) demonstrated that TRF downregulated oxidative stress-related genes (Nox1, Sod1, Gpx4), promoted mitochondrial fusion (Mfn1, Mfn2, Opa1), supported mitochondrial bioenergetics (Atp5e, Cox4i1) and inhibited apoptosis (Bax, Bcl2). Collectively, these findings establish that maternal TRF supplementation effectively counteracts allergic asthma–induced systemic inflammation and oxidative stress, thereby safeguarding early embryonic development. This work unveils a novel mechanistic link between maternal inflammation and oxidative stress-mitochondrial health-embryo viability while positioning TRF as a promising maternal nutraceutical to fortify embryonic resilience and improve reproductive success in inflammatory conditions.