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Pregnancy after cancer and chemotherapy: transgenerational effects

Grant number: 20/14248-8
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): April 05, 2021
Effective date (End): February 28, 2022
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Maria Cristina Cintra Gomes Marcondes
Grantee:Natália Miyaguti Angelo da Silva
Supervisor abroad: Jochen Springer
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Local de pesquisa : Charité - Universitätsmedizin Berlin, Germany  
Associated to the scholarship:19/13937-7 - Nutrition and Câncer. Molecular, Proteomic and Metabolomic aspects in experimental model of cachexia., BP.PD

Abstract

Cancer affects about 5% of women under 50 years. In Europe, women between 20 to 49 years had an incidence increase colon cancer, especially related to obesity. Currently, with an increased survival in cancer patients is possible the opportunity of a pregnancy after cancer treatment. Chemotherapeutic agents are one of the main cancer treatments and some problems related to infertility and epigenetics alterations are being studied as a consequence for a further pregnancy. The use of doxorubicin (DXR) as chemotherapy was already related to an increased risk of skeletal muscle damages and cardiotoxic effects. In relation to the offspring of mother who had chemotherapy treatment there is a lack of studies in this topic, some reported effects were relating epigenetics alterations and neonatal death, physical malformation, chromosomal aberrations on the offspring. Therefore, as cancer and chemotherapy a new problem faced to women in pregnancy age and with a lack of studies reporting the consequences of this treatment for a pregnancy and for the further generations, this project aims to characterize the phenotypic changes related to heart and skeletal muscle function of the F1 and F2 generations of female mice that had colon cancer and treated with DXR (F0 generation) before mating also evaluating the possible transgenerational epigenetic changes. For this purpose, animal and (colon) cancer model and doxorubicin will be applied to assess these changes. Classical techniques will be employed to access body composition and muscle and heart damages, such as DEXA, grip strength and echocardiography. Epigenetics techniques, such as pyrosequencing, will be also applied to determine possible epigenetics markers. Likewise, high technology techniques, such as MALDI-Imaging and OROROBOROS, will be applied to evaluate the differential proteins expressions and mitochondrial dysfunction.