Discrete placental gene expression signatures accompany diabetic disease classifications during pregnancy.
Am J Obstet Gynecol
; 2024 May 17.
Article
em En
| MEDLINE
| ID: mdl-38763341
ABSTRACT
BACKGROUND:
Gestational diabetes mellitus affects up to 10% of pregnancies and is classified into subtypes gestational diabetes subtype A1 (GDMA1) (managed by lifestyle modifications) and gestational diabetes subtype A2 (GDMA2) (requiring medication). However, whether these subtypes are distinct clinical entities or more reflective of an extended spectrum of normal pregnancy endocrine physiology remains unclear.OBJECTIVE:
Integrated bulk RNA-sequencing (RNA-seq), single-cell RNA-sequencing (scRNA-seq), and spatial transcriptomics harbors the potential to reveal disease gene signatures in subsets of cells and tissue microenvironments. We aimed to combine these high-resolution technologies with rigorous classification of diabetes subtypes in pregnancy. We hypothesized that differences between preexisting type 2 and gestational diabetes subtypes would be associated with altered gene expression profiles in specific placental cell populations. STUDYDESIGN:
In a large case-cohort design, we compared validated cases of GDMA1, GDMA2, and type 2 diabetes mellitus (T2DM) to healthy controls by bulk RNA-seq (n=54). Quantitative analyses with reverse transcription and quantitative PCR of presumptive genes of significant interest were undertaken in an independent and nonoverlapping validation cohort of similarly well-characterized cases and controls (n=122). Additional integrated analyses of term placental single-cell, single-nuclei, and spatial transcriptomics data enabled us to determine the cellular subpopulations and niches that aligned with the GDMA1, GDMA2, and T2DM gene expression signatures at higher resolution and with greater confidence.RESULTS:
Dimensional reduction of the bulk RNA-seq data revealed that the most common source of placental gene expression variation was the diabetic disease subtype. Relative to controls, we found 2052 unique and significantly differentially expressed genes (-2CONCLUSION:
Consistent with the distinct association of perinatal outcome risk, placentae from GDMA1, GDMA2, and T2DM-affected pregnancies harbor unique gene signatures that can be further distinguished by altered placental cellular subtypes and microarchitectural niches.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Am J Obstet Gynecol
Ano de publicação:
2024
Tipo de documento:
Article