Compromised global embryonic transcriptome associated with advanced maternal age.

Area of Science:

• Reproductive biology
• Genomics
• Developmental biology

Background:

• Advanced maternal age (AMA) is associated with decreased fertility and increased risk of pregnancy complications.
• Understanding the molecular mechanisms underlying these reproductive challenges is crucial for improving outcomes.

Purpose of the Study:

• To investigate the global transcriptome and associated embryonic molecular networks affected by advanced maternal age.
• To identify molecular signaling pathways critical for embryo development that are altered in AMA.

Main Methods:

• Blastocysts from women aged ≥42 years (AMA) and younger donors (<30 years) were collected.
• RNA sequencing was performed on blastocysts to analyze global gene expression.
• Bioinformatics and qPCR were used for pathway analysis and gene expression validation.

Main Results:

• A total of 2688 differentially expressed transcripts were identified between AMA and young donor blastocysts.
• 95% of these transcripts showed decreased transcription in AMA blastocysts.
• Altered molecular signaling networks, including CREBBP, ESR1, and SP1, were identified as critical for embryo development.

Conclusions:

• Blastocysts from AMA women exhibit a significantly decreased global transcriptome.
• The ESR1/SP1/CREBBP pathway is a key upstream regulator impacted in AMA embryos.
• These molecular alterations compromise embryonic cell signaling, proliferation, and implantation, leading to poorer reproductive outcomes.