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Infertility diagnosis has a significant impact on the transcriptome of developing blastocysts

McCallie, Blair R., Parks, Jason C., Griffin, Darren K., Schoolcraft, William B., Katz-Jaffe, Mandy G. (2017) Infertility diagnosis has a significant impact on the transcriptome of developing blastocysts. Molecular Human Reproduction, 23 (8). pp. 549-556. ISSN 1360-9947. E-ISSN 1460-2407. (doi:10.1093/molehr/gax034) (KAR id:62408)

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Abstract

STUDY QUESTION: Is the human blastocyst transcriptome associated with infertility diagnosis, specifically: polycystic ovaries (PCO), male factor (MF) and unexplained (UE)?

WHAT IS KNOWN ALREADY: Infertility diagnosis has an impact on the probability for a successful outcome following an IVF cycle. Limited information is known regarding the relationship between a specific infertility diagnosis and blastocyst transcription during preimplantation development.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Surplus cryopreserved blastocysts were donated with patient consent and institutional review board approval. Female patients were <38 years old with male patients <40 years old. Blastocysts were grouped according to infertility diagnosis: PCO (n = 50), MF (n = 50), UE (n = 50) and fertile donor oocyte controls (n = 50). Pooled blastocysts were lysed for RNA isolation followed by microarray analysis using the SurePrint G3 Human Gene Expression Microarray. Validation was performed on significant genes of interest using real-time quantitative PCR (RT-qPCR).

MAIN RESULTS AND THE ROLE OF CHANCE: Transcription alterations were observed for all infertility etiologies compared to controls, resulting in differentially expressed genes: PCO = 869, MF = 348 and UE = 473 (P < 0.05; >2-fold). Functional annotation of biological and molecular processes revealed both similarities, as well as differences, across the infertility groups. All infertility etiologies displayed transcriptome alterations in signal transducer activity, receptor binding, reproduction, cell adhesion and response to stimulus. Blastocysts from PCO patients were also enriched for apoptotic genes while MF blastocysts displayed enrichment for genes involved in cancer processes. Blastocysts from couples with unexplained infertility displayed transcription alterations related to various disease states, which included mechanistic target of rapamycin (mTOR) and adipocytokine signaling. RT-qPCR validation confirmed differential gene expression for the following genes: BCL2 like 10 (BCL2L10), heat shock protein family A member 1A (HSPA1A), heat shock protein family A member 1B (HSPA1B), activating transcription factor 3 (ATF3), fibroblast growth factor 9 (FGF9), left-right determination factor 1 (LEFTY1), left-right determination factor 2 (LEFTY2), growth differentiation factor 15 (GDF15), inhibin beta A subunit (INHBA), adherins junctions associated protein 1 (AJAP1), cadherin 9 (CDH9) and laminin subunit alpha 4 (LAMA4) (P < 0.05; >2-fold).

Item Type: Article
DOI/Identification number: 10.1093/molehr/gax034
Uncontrolled keywords: polycystic ovaries, male factor, unexplained Infertility, transcriptome, gene expression
Subjects: Q Science
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Darren Griffin
Date Deposited: 27 Jul 2017 10:41 UTC
Last Modified: 23 Jan 2020 04:13 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/62408 (The current URI for this page, for reference purposes)
Griffin, Darren K.: https://orcid.org/0000-0001-7595-3226
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