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Free Radic Biol Med. 2025 Aug 14:S0891-5849(25)00902-5. doi: 10.1016/j.freeradbiomed.2025.08.023. Online ahead of print.
ABSTRACT
It is widely accepted that the poor quality of in vitro-produced (IVP) embryos becomes one of the most intractable issues currently limiting the outcomes of human assisted reproductive technology (ART). Although diverse molecules and pathways may be involved in this process, strategies to optimize culture conditions for the improvement of embryo development potential and the relevant mechanisms remain underexplored. Here, we demonstrate that the supplementation of C-type natriuretic peptide (CNP), a potential embryokine present in the oviduct, can improve the blastocyst formation rate and embryo quality, as evidenced by an increased total cell number and inner cell mass (ICM) cells, elevated embryonic cell proliferation, and reduced embryonic cell apoptosis. RNA-sequencing analysis suggests that CNP may regulate biological processes related to lipid metabolism and redox homeostasis in early embryos. Furthermore, our results reveal that CNP significantly reduces lipid droplet content, fatty acid storage, and the expression of lipogenesis-related genes. Notably, we show that CNP alleviates the elevated reactive oxygen species (ROS) levels and lipid peroxidation in in vitro embryos. These findings demonstrate that CNP supplementation is a feasible and effective approach to prevent deterioration in embryo quality and improve developmental potential by inhibiting excessive lipid droplet accumulation and elevated oxidative stress in embryos. Collectively, our study not only provides new insights into understanding the crosstalk between early mammalian embryos and the maternal reproductive tract but also presents a promising strategy for improving the success rate of human ART.
PMID:40816650 | DOI:10.1016/j.freeradbiomed.2025.08.023