Epigenetic effects of maternal exposure to nicotine on the rats placenta

• Grant number: 24/10707-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2024
• End date: September 30, 2025
• Field of knowledge: Biological Sciences - Morphology - Embryology
• Principal Investigator: Camila Cicconi Paccola
• Grantee: Luiza Bacha Cardoso
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Nicotine consumption during pregnancy is responsible for changes in embryonic and fetal development, which may have an epigenetic origin. The main epigenetic mechanisms consist of the addition of chemical groups directly to the DNA (where they interfere with the access of the enzyme responsible for transcription) or to histones (impacting on DNA compaction), and which do not affect the DNA sequence, but interfere with gene transcription. Current researches link epigenetic changes with pre-eclampsia, intrauterine growth restriction, spontaneous abortion, congenital malformations and metabolic disorders. However, it is still necessary to elucidate the molecular mechanisms by which nicotine triggers this clinical condition. Thus, the goal of this work is to evaluate the possible histological and/or epigenetic changes caused by exposure to nicotine in the placenta of second-generation albino rats after maternal exposure. For this, pregnant rats will receive an osmotic pump containing 2mg/kg/day of nicotine from the first day of pregnancy, in order to expose the offspring throughout the pregnancy. This pump will be refilled on the 1st day after the birth of the offspring, ensuring exposure to nicotine through breastfeeding. The female offspring will be euthanized on the 90th postnatal day, when the placenta and fetus will be collected. The placentas will be fixed and subjected to immunohistochemical labeling of the cells using a specific antibody for DNA methylation (DNMT-1), histone methylation (H3K9) and histone acetylation (HDAC-4) to understand how the placental epigenetic phenomena related to nicotine occur.