TY - JOUR
T1 - Pro-inflammatory immune cell gene expression during the third trimester of pregnancy is associated with shorter gestational length and lower birthweight
AU - Ross, Kharah M.
AU - Carroll, Judith E.
AU - Dunkel Schetter, Christine
AU - Hobel, Calvin
AU - Cole, Steve W.
N1 - Publisher Copyright:
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Problem: Altered maternal immune function predicts risk for shorter gestation and low birthweight. Few studies examine associations between prenatal immune cell gene expression and gestational length or birthweight. No studies examine which cell types drive associations. The purpose of this study is to explore associations between peripheral blood immune cell gene expression and gestational length and birthweight, using transcript origin analysis. Method of study: Eighty-nine women were drawn from the Community Child Health Network cohort. Third trimester maternal dried blood spots were used for genome-wide transcriptional (mRNA) profiling. Gestational length and birthweight were obtained from medical charts. Covariates were age, race/ethnicity, pre-pregnancy body mass index, smoking, gestational age at blood sampling, and pregnancy infections. Associations between gene expression profiles and gestational length and birthweight were tested using general linear models. The Transcription Element Listening System (TELiS) bioinformatics analysis quantified upstream transcription factor activity. Transcript origin analysis identified leukocyte subsets mediating observed effects. Results: Shorter gestation was predicted by increased NF-kB (TFBM ratio = −0.582 ± 0.172, P <.001) and monocyte activity (diagnosticity score = 0.172 ± 0.054, P <.001). Longer gestation was associated with increased dendritic cell activity (diagnosticity score = 0.194 ± 0.039, P <.001). Increased AP-1 activity predicted lower birthweight (TFBM ratio = −0.240 ± 0.111, P =.031). Dendritic cells and CD4+ and CD8+ T cells predicted birthweight-related gene expression differences (diagnosticity score P's < 0.021). Conclusion: Higher third trimester pro-inflammatory gene expression predicted shorter gestation and lower birthweight. Variations in monocyte and dendritic cell biology contributed to both effects, and T-cell biology contributed to higher birthweight. These analyses clarify the role of myeloid/lymphoid lineage immune regulation in pregnancy outcomes.
AB - Problem: Altered maternal immune function predicts risk for shorter gestation and low birthweight. Few studies examine associations between prenatal immune cell gene expression and gestational length or birthweight. No studies examine which cell types drive associations. The purpose of this study is to explore associations between peripheral blood immune cell gene expression and gestational length and birthweight, using transcript origin analysis. Method of study: Eighty-nine women were drawn from the Community Child Health Network cohort. Third trimester maternal dried blood spots were used for genome-wide transcriptional (mRNA) profiling. Gestational length and birthweight were obtained from medical charts. Covariates were age, race/ethnicity, pre-pregnancy body mass index, smoking, gestational age at blood sampling, and pregnancy infections. Associations between gene expression profiles and gestational length and birthweight were tested using general linear models. The Transcription Element Listening System (TELiS) bioinformatics analysis quantified upstream transcription factor activity. Transcript origin analysis identified leukocyte subsets mediating observed effects. Results: Shorter gestation was predicted by increased NF-kB (TFBM ratio = −0.582 ± 0.172, P <.001) and monocyte activity (diagnosticity score = 0.172 ± 0.054, P <.001). Longer gestation was associated with increased dendritic cell activity (diagnosticity score = 0.194 ± 0.039, P <.001). Increased AP-1 activity predicted lower birthweight (TFBM ratio = −0.240 ± 0.111, P =.031). Dendritic cells and CD4+ and CD8+ T cells predicted birthweight-related gene expression differences (diagnosticity score P's < 0.021). Conclusion: Higher third trimester pro-inflammatory gene expression predicted shorter gestation and lower birthweight. Variations in monocyte and dendritic cell biology contributed to both effects, and T-cell biology contributed to higher birthweight. These analyses clarify the role of myeloid/lymphoid lineage immune regulation in pregnancy outcomes.
KW - birthweight
KW - gene expression
KW - gestational length
KW - immune cells
KW - mRNA
UR - http://www.scopus.com/inward/record.url?scp=85074095256&partnerID=8YFLogxK
U2 - 10.1111/aji.13190
DO - 10.1111/aji.13190
M3 - Journal Article
C2 - 31529581
AN - SCOPUS:85074095256
SN - 1046-7408
VL - 82
JO - American Journal of Reproductive Immunology
JF - American Journal of Reproductive Immunology
IS - 6
M1 - e13190
ER -