Genetic Mutations and Non-Genomic Dysregulation in Human Preimplantation Embryo Arrest

Area of Science:

• Reproductive Biology
• Developmental Biology
• Genetics

Background:

• Human preimplantation embryo arrest (PREMBA) is a significant challenge in assisted reproductive technology (ART), affecting approximately 10% of in vitro fertilized (IVF) embryos.
• Genetic mutations have been identified as a cause of PREMBA, disrupting crucial developmental pathways.
• However, the etiology of most clinical PREMBA cases remains unexplained, with multi-omics abnormalities observed.

Purpose of the Study:

• To provide a comprehensive overview of the molecular mechanisms underlying human preimplantation embryo arrest (PREMBA).
• To categorize PREMBA causes into known genetic mutations and unexplained factors.
• To highlight the diverse molecular disruptions associated with unexplained PREMBA.

Main Methods:

• Review of existing literature, including whole-exome sequencing (WES) studies.
• Analysis of multi-omics data from unexplained PREMBA cases.
• Categorization of molecular mechanisms based on genetic mutations and other abnormalities.

Main Results:

• Identified genetic mutations affecting maternal mRNA clearance, subcortical maternal complex, DNA repair, spindle assembly, cell cycle, and nuclear transport.
• Documented widespread multi-omics abnormalities in unexplained PREMBA, including transcriptional arrest, DNA hypermethylation, altered chromatin accessibility, aberrant histone modification, aneuploidy, and senescence.
• Highlighted the complexity and multifactorial nature of PREMBA.

Conclusions:

• PREMBA is caused by both identifiable genetic mutations and complex, multifactorial molecular abnormalities.
• Further research into unexplained PREMBA is crucial for improving ART outcomes.
• Understanding these mechanisms can guide diagnostic and therapeutic strategies for infertility.