Screening of placental genomic imprinting processes on DLK1-DIO3 locus in hypothyroid patients: involvement of T3 in offspring's DM2 susceptibility

• Grant number: 18/06178-0
• Support type: Regular Research Grants
• Duration: December 01, 2019 - July 31, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal researcher: Celia Regina Nogueira
• Grantee: Celia Regina Nogueira
• Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated scholarship(s): 20/12289-9 - Screening of placental genomic imprinting processes on DLK1-DIO3 locus in hypothyroid patients: involvement of T3 in offspring's DM2 susceptibility, BP.TT; 19/25177-7 - Screening of placental genomic imprinting processes on DLK1-DIO3 locus in hypothyroid patients: involvement of T3 in offspring's DM2 susceptibility, BP.TT

Abstract

The thyroid hormone is widely involved in metabolic control processes, from fetal development to adulthood. Environmental disruptors in the gestational period, which could affect epigenetic control-ling processes, may predispose the susceptibility to metabolic diseases in adult life, like diabetes mellitus type 2. Although many studies have been associated with a reduction in Dio3 mRNA expression to altered DNA methylation status on imprinted DLK1-DIO3 locus with the occurrence of glucose intolerance, the exact mechanisms have not been fully elucidated. Thus, our hypothesis it's that hypothyroidism may be considered a disruptive factor in placental imprinting mechanisms, conferring susceptibility to the development of T2DM. Therefore, the aim of this study is to compare the gene expression profile and the methylation status of DLK1-DIO3 locus in placentas from hypothyroid patients. To do this, 70 patients will be recruited, which will subdivided in 2 groups of hypothyroidism and healthy pregnant and we will carry out the comparative study of the methylation profile of placental DNA by pyrosequenciation (Pyromark Q24) after bisulfite conversion of IG- DMR and MEG3 -DMR in addition to the expression profile of mRNA by qRT-PCR. The comparison between proportions among groups will be calculated with Chi-Square Test, the minimum significative difference between groups will be 40%, with 80% power and significance of 1%. (AU)