Gabriela Fontana de Mesquita1, Fernanda Aparecida Marqueto 1, Carla de Moraes Salgado1, Rafaela Trevisan Scandiuzzu1, Leisa Lopes Aguiar1, Beatriz Cassaniga Talassi1, Mauricio Luiz Sforça2, Silvana Aparecida Rocco2, Gustavo Henrique Rodrigues da Silva2, Guilherme de Moraes Nobrega3, Fernanda garanhani de castro surita 3, Maria Cristina Cintra Gomes Marcondes1, Maria Laura Costa do Nascimento3, Lais Rosa Viana 1
The incidence of cancer during pregnancy, estimated at 1 case per 1,000 pregnancies, has been progressively increasing, driven by delayed childbearing. In this context, breast cancer is the most prevalent type and the chemotherapy is the main treatment option. Either the cancer and chemotherapy agents may lead to impairments in the maintenance of a healthy pregnancy. The placenta, as a fundamental organ at the maternal-fetal interface, may undergo morphological and functional changes in response to tumor growth and exposure to chemotherapy, although the underlying mechanisms remain poorly understood. This study aimed to characterize the placental metabolomic profile of pregnant women with breast cancer treated with chemotherapy (Case group, n = 6), compared to healthy pregnant women (Control group, n = 7). Samples were collected from three regions of the placenta: the chorionic villi, basal plate, and chorionic plate. All samples were obtained from the CAISM/UNICAMP Biobank. Metabolite extraction was performed using solutions of chloroform and methanol. The analyses were performed using 600 MHz Nuclear Magnetic Resonance (NMR) spectroscopy. Metabolite identification and quantification were carried out using Chenomx NMR Suite 8.3 software, and statistical analysis was conducted on the MetaboAnalyst 6.0 platform, considering p < 0.05 and log2 fold change ≥ 0.58 as significance criteria. A total of 51 metabolites were identified, with 39 differentially expressed in the chorionic villi and 23 in the basal plate. On the other hand, analysis of the chorionic plate did not reveal statistically significant metabolic alterations between the groups. In the chorionic villi, alterations were observed in metabolic pathways such as the urea cycle, ammonia recycling, glycine and serine metabolism, and aspartate metabolism. In the basal plate, the most affected pathways included the one-carbon pool by folate, glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, pantothenate and Coenzyme A biosynthesis, as well as phenylalanine, tyrosine, and tryptophan biosynthesis. These findings reinforce that breast cancer and chemotherapy treatment during pregnancy promote important metabolic changes in the placenta, with potential impacts on the intrauterine environment and fetal development.
Agradecimentos: FAPESP-2024/00147-6; 2021/08931-0; 2017/02739-4; CAISM - Hospital da Mulher Prof. Dr. José Aristodemo Pinotti (UNICAMP); Institute of Biology of the State University of Campinas - IB/Unicamp;CNPEM - National Center for Research in Energy and Materials - LNBIO