In vitro post-implantation development of aneuploid human embryos: a study of self-correction and maternal age impact

• Grant number: 21/11313-6
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2022
• End date: June 30, 2024
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Eduardo Leme Alves da Motta
• Grantee: Eduardo Leme Alves da Motta
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Ivone Cipriano Oyama

Abstract

Chromosomal errors at the time of segregation or recombination during oocyte meiosis caused the most aneuploidies in humans. These abnormalities are related to cohesins and mitochondrial dysfunctions, telomeres shortening and meiotic spindle instability, mainly in women over 40 years old. However, several lines of evidence support the idea that aneuploidy is common and not a definitive event found in the early stages of mammalian embryos. Given the possibility of self-correction mechanisms existence in these embryos, this study intends to investigate whether aneuploid blastocysts could be rescued for an euploid condition after in vitro culture through post-implantation stage. To address this question, aneuploid embryos will be selected from two groups with different maternal ages: Group I, women aged d 37 years and Group II, women aged e 38 years. The blastocysts will be thawed and cultured for up to 12 days in the absence of maternal tissues. After this period, embryos will be analyzed by the following methodologies: (1) NGS technique for aneuploidy detection in D12 embryos after rebiopsy; (2) TUNEL-Fluorescein method for detection of apoptosis in embryonic cells; (3) Immunofluorescent staining for identification of cell differentiation markers such as OCT-3/4, GATA6, CK7 and F-actin; and (4) Transmission and scanning electron microscopy for analysis of embryo surface morphology and ultrastructural features. These techniques will allow us to verify whether the cellular and chromosomal status could be stable after extended embryonic culture system, relating to the selected age profiles. (AU)