Compromised global embryonic transcriptome associated with advanced maternal age

McCallie, Blair R., Parks, Jason C., Trahan, G. Devon, Jones, Kenneth L., Coate, Breanne D., Griffin, Darren K., Schoolcraft, William B., Katz-Jaffe, Mandy G. (2019) Compromised global embryonic transcriptome associated with advanced maternal age. Journal of Assisted Reproduction and Genetics, . ISSN 1058-0468. (doi:10.1007/s10815-019-01438-5)

Abstract

Purpose To investigate the global transcriptome and associated embryonic molecular networks impacted with advanced maternal age (AMA). Methods Blastocysts derived from donor oocyte IVF cycles with no male factor infertility (< 30 years of age) and AMA blastocysts (≥ 42 years) with no other significant female factor infertility or male factor infertility were collected with informed patient consent. RNA sequencing libraries were prepared using the SMARTer® Ultra® Low Kit (Clontech Laboratories) and sequenced on the Illumina HiSEQ 4000. Bioinformatics included Ingenuity® Pathway Analysis (Qiagen) with ViiA™7 qPCR utilized for gene expression validation (Applied Biosystems). Results A total of 2688 significant differentially expressed transcripts were identified to distinguish the AMA blastocysts from young, donor controls. 2551 (95%) of these displayed decreased transcription in the blastocysts from older women. Pathway analysis revealed three altered molecular signaling networks known to be critical for embryo and fetal development: CREBBP, ESR1, and SP1. Validation of genes within these networks confirmed the global decreased transcription observed in AMA blastocysts (P < 0.05). Conclusions A significant, overall decreased global transcriptome was observed in blastocysts from AMA women. The ESR1/SP1/CREBBP pathway, in particular, was found to be a highly significant upstream regulator impacting biological processes that are vital during embryonic patterning and pre-implantation development. These results provide evidence that AMA embryos are compromised on a cell signaling level which can repress the embryo’s ability to proliferate and implant, contributing to a deterioration of reproductive outcomes.

Item Type:	Article
DOI/Identification number:	10.1007/s10815-019-01438-5
Uncontrolled keywords:	Advanced maternal age, Human blastocyst, Transcriptome, Gene expression
Divisions:	Faculties > Sciences > School of Biosciences
Depositing User:	Sue Davies
Date Deposited:	07 May 2019 08:16 UTC
Last Modified:	28 May 2019 14:59 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/73775 (The current URI for this page, for reference purposes)
Griffin, Darren K.:	https://orcid.org/0000-0001-7595-3226