Molecular aspects of placentas from pregnant Wistar rats carrying Walker 256 tumor. Assessment of the effects of tumor growth and exposure to chemotherapy treatment during pregnancy.

• Grant number: 25/00592-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2025
• End date: February 28, 2027
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Laís Rosa Viana
• Grantee: Fernanda Aparecida Marqueto
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/08931-0 - Cancer and pregnancy: proteomic, transcriptomic and metabolic alterations in placenta from pregnant women with cancer and Wistar pregnant Walker 256 tumour-bearing rats, AP.JP

Abstract

Cancer during pregnancy is a rare event, with approximately 1:1000 pregnancies complicated by maternal cancer, of which breast cancer during pregnancy (PrBC) is the most frequent. Among the available treatment options in this context, chemotherapy is the most commonly used, administered starting from the second trimester of pregnancy. Both the tumor and chemotherapy act as stressors to the placenta and the baby, impairing fetal development, such as causing intrauterine growth restriction and prematurity. Despite the clinical relevance of this topic, little is known about the molecular-level changes occurring in this context of cancer during pregnancy. Taurine is a non-essential amino acid, produced mainly by the liver and synthesized through the cysteine synthesis pathway, with promising effects in the context of neuromodulation, angiogenesis, fetal development, and the potential to minimize the effects of chemotherapy treatments. Therefore, we hypothesize that taurine supplementation has a beneficial effect on the placenta and, consequently, on fetal development in the face of cancer and chemotherapy treatment during pregnancy. The objective of this project is to investigate changes in the metabolomic profile of maternal and fetal serum, as well as evaluate the placental metabolomic profile of pregnant Wistar rats bearing the Walker 256 tumor treated with the chemotherapeutic agents doxorubicin and cyclophosphamide, with or without taurine supplementation. The following experimental groups will be formed: 1) healthy pregnant rats (Control group); 2) pregnant rats with a tumor (Cancer group); 3) pregnant rats with a tumor and chemotherapy treatment (Cancer + Chemo group); 4) pregnant rats with a tumor and chemotherapy treatment associated with taurine (Cancer + Chemo + Tau group). To this end, two days after pregnancy identification, the Walker 256 tumor will be implanted, where approximately 1x10¿ viable cells will be inoculated subcutaneously into the right flank of the rats in the Cancer, Cancer + Chemo, and Cancer + Chemo + Tau groups. Regarding chemotherapy treatment, two cycles of intraperitoneal administration of doxorubicin (0.1 mg/kg) and cyclophosphamide (1 mg/kg) will be performed every three days after the first trimester of pregnancy (days 14 and 17). Taurine supplementation will be administered concomitantly with tumor inoculation, on day 2 of pregnancy, where rats in the Cancer + Chemo + Tau group will receive 2.5% taurine in water until the day of euthanasia (day 20). On this day, maternal and fetal blood will be collected, as well as placentas and fetuses, which will be weighed and stored for future metabolomic profile analyses.