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Profiles of gene expression in maternal blood predict offspring birth weight in normal pregnancy

Published online by Cambridge University Press:  17 June 2019

Thomas W. McDade*
Affiliation:
Department of Anthropology, Northwestern University, Evanston, IL, USA Institute for Policy Research, Northwestern University, Evanston, IL, USA Child and Brain Development Program, Canadian Institute for Advanced Research, Toronto, Ontario, Canada
Chris W. Kuzawa
Affiliation:
Department of Anthropology, Northwestern University, Evanston, IL, USA Institute for Policy Research, Northwestern University, Evanston, IL, USA
Judith Borja
Affiliation:
USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City, Philippines Department of Nutrition and Dietetics, University of San Carlos, Cebu City, Philippines
Jesusa M. G. Arevalo
Affiliation:
Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA, USA
Greg Miller
Affiliation:
Institute for Policy Research, Northwestern University, Evanston, IL, USA Department of Psychology, Northwestern University, Evanston, IL, USA
Steve W. Cole
Affiliation:
Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA, USA Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles School of Medicine, Los Angeles, CA, USA

Abstract

The association between lower birth weight and increased disease risk in adulthood has drawn attention to the physiological processes that shape the gestational environment. We implement genome-wide transcriptional profiling of maternal blood samples to identify subsets of genes and associated transcription control pathways that predict offspring birth weight. Female participants (N = 178, mean = 27.0 years) in a prospective observational birth cohort study were contacted between 2009 and 2014 to identify new pregnancies. An in-home interview was scheduled for early in the third trimester (mean = 30.3 weeks) to collect pregnancy-related information and a blood sample, and birth weight was measured shortly after delivery. Transcriptional activity in white blood cells was determined with a whole-genome gene expression direct hybridization assay. Fifty transcripts were differentially expressed in association with offspring birth weight, with 18 up-regulated in relation to lower birth weight, and 32 down-regulated. Examination of transcription control pathways identified increased activity of NF-κB, AP-1, EGR1, EGR4, and Gfi families, and reduced the activity of CEBP, in association with lower birth weight. Transcript origin analyses identified non-classical CD16+ monocytes, CD1c+ myeloid dendritic cells, and neutrophils as the primary cellular mediators of differential gene expression. These results point toward a systematic regulatory shift in maternal white blood cell activity in association with lower offspring birth weight, and they suggest that analyses of gene expression during gestation may provide insight into regulatory and cellular mechanisms that influence birth outcomes.

Type
Original Article
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2019 

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