JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):72
Oral Presentation
29th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263634
P-60. Distinctive Metabolomic Signatures in Euploid Versus Aneuploid Embryo Culture Media: Implications for Embryonic Development
Edson Guimarães lo Turco1, Anna Virginia Pike1, Luana Gallego Adami2, Rafaela Aguiar Ferreira3, Kahisa Fontana dal Toso4, Eliana Morita Yokota3, Lidio Jair Ribas Centa4, Caroline Pais de Carvalho5, Marcos Nogueira Eberlin5, Fernando Prado Ferreira6
1 Universidade Federal de São Paulo - Departamento de Cirurgia, Disciplina de Urologia, Setor de Reprodução Humana - São Paulo - SP - Brasil
2 Embriológica Assessoria em Reproducao Assistida - São Paulo - SP - Brasil
3 Citi Medicina Reprodutiva - Centro Completo de Investigação e Tratamento da Infertilidade - São Paulo - SP - Brasil
4 Androlab - Clínica e Laboratório de Reprodução Humana e Andrologia - Curitiba - PR - Brasil
5 Universidade Presbiteriana Mackenzie, MackGraphe - Instituto Mackenzie de Pesquisas em Grafeno e Nanotecnologias - São Paulo - SP - Brasil
6 Clínica Neo Vita - São Paulo - São Paulo - Brasil
Objective: To characterize the metabolomic profile differences in culture media between euploid and aneuploid embryos using mass spectrometry, and to elucidate the metabolic pathways affected by chromosomal abnormalities during early embryonic development.
Methods: This study was approved by Ethics Committee (61297622.5.0000.5505). Culture media from morphologically similar day 5 blastocysts (n=40) were analyzed following genetic testing for chromosomal status (19 euploid, 21 aneuploid). Untargeted metabolomics analysis was performed using high-resolution mass spectrometry (MALDI-OrbiTrap). Molecular attribution was conducted using multiple databases (Human Metabolome Database, Kyoto Encyclopedia of Genes and Genomes, LipidMaps, MeTLin, PubChem). Metabolic pathway analysis was subsequently performed to identify differentially regulated biochemical processes.
Results: Significant differences in low molecular weight ions were observed between euploid and aneuploid embryo culture media. Euploid embryos exhibited balanced energy metabolism markers (adenosine monophosphate (AMP): m/z 250.01; adenosine diphosphate (ADP): m/z 328.05), normal phospholipid turnover (phosphatidylcholine: m/z 674.17; lysophospholipids: m/z 487.19), and regulated one-carbon metabolism components (S-adenosylmethionine: m/z 386.09; S-adenosylhomocysteine: m/z 388.07). In contrast, aneuploid embryos showed distinctive metabolite alterations, including elevated oxidized glutathione (m/z 313.05) suggesting increased oxidative stress, dysregulated phosphoinositide signaling (m/z 517.21, 896.29), and altered energy metabolism (nicotinamide adenine dinucleotide (NAD+) derivatives: m/z 638.15). These changes indicate impairments in multiple interconnected pathways critical for embryonic development, including energy metabolism, membrane integrity, epigenetic regulation, and cellular signaling.
Conclusion: This study reveals that chromosomal abnormalities are associated with systemic metabolic dysregulation in preimplantation embryos, with the embryonic chromosomal status significantly influencing metabolic profiles in culture media. The distinctive metabolomic signatures identified between euploid and aneuploid embryos reflect fundamental differences in biochemical processes that may determine developmental competence and implantation potential. These findings provide insight into the biochemical consequences of aneuploidy, suggest potential mechanisms underlying reduced implantation potential, and may contribute to the development of non-invasive metabolite biomarkers for embryo selection, as well as potential targets for therapeutic interventions to improve embryonic development outcomes.