TOXICOLOGY RESEARCH, cilt.14, sa.6, 2025 (SCI-Expanded, Scopus)
Hypoxia, during early embryonic development, causes morphological and functional impairments through oxidative stress. Melatonin, a strong antioxidant, may exert potential protective effects in this process. This study investigated the effects of melatonin on yolk sac vascularization and embryonic development in rat embryos exposed to hypoxia. Rat embryos at gestational day 9.5 were cultured for 48 h using a whole embryo culture (WEC) system. Embryos were divided into six groups: Control (C), Hypoxia (H), 10 mu M Melatonin (10 mu M Mel), Hypoxia +10 mu M Melatonin (H + 10 mu M Mel), 50 mu M Melatonin (50 mu M Mel), and Hypoxia +50 mu M Melatonin (H + 50 mu M Mel). At the end of culture, morphological parameters, oxidative stress markers, and the distribution of vWF-positive cells were evaluated. Compared with the control group, the H group exhibited marked developmental delay and vascularization defects (P < 0.05). Melatonin administration significantly reduced these abnormalities, with the 50 mu M melatonin group showing the most prominent improvements in morphological development, oxidative stress parameters, and vascularization (P < 0.05). Melatonin provides protective effects against hypoxia-induced early embryonic developmental impairments and holds therapeutic potential as an agent supporting development during the early intrauterine period. Highlights center dot This study experimentally investigated hypoxia-induced embryonic developmental defects using the Whole Embryo Culture (WEC) model and evaluated the potential effects of melatonin, applied at different doses, on embryo and yolk sac development. center dot The therapeutic potential of melatonin was examined with a multidimensional approach, combining morphological assessment, immunohistochemical analysis (distribution of vWF-positive cells), and biochemical oxidative stress parameters. center dot Findings revealed that embryos exposed to hypoxia showed developmental delay, vascularization defects, and increased oxidative stress; melatonin administration significantly reduced these pathological changes. center dot The main aim was to determine whether melatonin plays a protective role during early embryogenesis through antioxidant, anti-apoptotic, anti-inflammatory, and vasculogenic mechanisms. Results indicated that melatonin may serve as a potential therapeutic agent against hypoxia-induced embryonic damage.