Genome-wide assessment of DNA methylation alterations induced by superovulation, sexual immaturity and in vitro follicle growth in mouse blastocysts

Clinical Epigenetics

Research

Felix Krueger¹  Elena Ivanova²  Gavin Kelsey³  Ellen Anckaert⁴  Johan Smitz⁴  Katy Billooye⁴  Laura Saucedo-Cuevas⁴  Anamaria-Cristina Herta⁴ 

[1] Altos Labs, Bioinformatics Group, CB21 6GP, Cambridge, UK;Epigenetics Programme, Babraham Institute, CB22 3AT, Cambridge, UK;Epigenetics Programme, Babraham Institute, CB22 3AT, Cambridge, UK;Centre for Trophoblast Research, University of Cambridge, CB2 3EG, Cambridge, UK;Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, CB2 0QQ, Cambridge, UK;Follicle Biology Laboratory (FOBI), UZ Brussel, Vrije Universiteit Brussel, Laarbeeklaan, Brussels, Belgium;

关键词: Oocyte;    Embryo;    Superovulation;    Imprinted genes;    DNA methylation;    In vitro follicle culture;   

DOI  :  10.1186/s13148-023-01421-z

 received in 2022-06-19, accepted in 2023-01-03,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundIn their attempt to fulfill the wish of having children, women who suffer from fertility issues often undergo assisted reproductive technologies such as ovarian stimulation, which has been associated with adverse health outcomes and imprinting disorders in children. However, given the crucial role of exogenous hormone stimulation in improving human infertility treatments, a more comprehensive analysis of the potential impacts on DNA methylation in embryos following ovarian stimulation is needed. Here, we provide genome-wide DNA methylation profiles of blastocysts generated after superovulation of prepubertal or adult mice, compared with blastocysts derived from non-stimulated adult mice. Additionally, we assessed the impact of the in vitro growth and maturation of oocytes on methylation in blastocysts.ResultsNeither hormone stimulation nor sexual maturity had an impact on the low global methylation levels characteristic of the blastocyst stage or was associated with extensive DNA methylation alterations. However, we found hormone- and age-associated changes at specific positions but dispersed throughout the genome. In particular, we detected anomalous methylation at a limited number of CpG islands. Additionally, superovulation in adult mice was associated with alterations at the Sgce and Zfp777 imprinted genes. On the other hand, in vitro culture of follicles from the early pre-antral stage was associated with globally reduced methylation and increased variability at imprinted loci in blastocysts.ConclusionsOur results indicate a minimal effect of ovarian stimulation of adult and prepubertal mice on the DNA methylation landscape attained at the blastocyst stage, but potentially greater impacts of in vitro growth and maturation of oocytes. These findings have potential significance for the improvement of assisted reproductive techniques, in particular for those related to treatments in prepubertal females, which could be crucial for improving human fertility preservation strategies.

【 授权许可】

CC BY   
© The Author(s) 2023

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