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Increased birth weight is associated with altered gene expression in neonatal foreskin

Published online by Cambridge University Press:  09 May 2017

L. J. Reynolds ,
R. I. Pollack ,
R. J. Charnigo ,
C. S. Rashid ,
A. J. Stromberg ,
S. Shen ,
J. M. O’Brien  and
K. J. Pearson
L. J. Reynolds
Affiliation:
Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA
R. I. Pollack
Affiliation:
Department of Obstetrics and Gynecology, College of Medicine, University of Kentucky, Lexington, KY, USA
R. J. Charnigo
Affiliation:
Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY, USA Department of Statistics, University of Kentucky, Lexington, KY, USA
C. S. Rashid
Affiliation:
Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA
A. J. Stromberg
Affiliation:
Department of Statistics, University of Kentucky, Lexington, KY, USA
S. Shen
Affiliation:
Department of Statistics, University of Kentucky, Lexington, KY, USA
J. M. O’Brien
Affiliation:
Department of Obstetrics and Gynecology, College of Medicine, University of Kentucky, Lexington, KY, USA
K. J. Pearson*
Affiliation:
Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA
*
*Address for correspondence: K. J. Pearson, 900 South Limestone, Wethington Room 591 Lexington, KY 40536, USA. (Email kevin.pearson@uky.edu)
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Abstract

Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n=7) v. the remainder of the cohort (n=40). Multivariate linear regression models were fit to relate expression levels on differentially expressed genes to birth weight group with adjustment for variables selected from a list of maternal and infant characteristics. Glucose transporter type 4 (GLUT4), insulin receptor substrate 2 (IRS2), leptin receptor (LEPR), lipoprotein lipase (LPL), low-density lipoprotein receptor-related protein 1 (LRP1), matrix metalloproteinase 2 (MMP2), plasminogen activator inhibitor-1 (PAI-1) and transcription factor 7-like 2 (TCF7L2) were significantly upregulated and histone deacetylase 1 (HDAC1) and thioredoxin (TXN) downregulated in the larger birth weight neonates v. controls. Multivariate modeling revealed that the estimated adjusted birth weight group difference exceeded one standard deviation of the expression level for eight of the 10 genes. Between 25 and 50% of variation in expression level was explained by multivariate modeling for eight of the 10 genes. Gene expression related to glycemic control, appetite/energy balance, obesity and inflammation were altered in tissue from babies with elevated birth weight, and these genes may provide important information regarding fetal programming in macrosomic babies.

Keywords

circumcisionfetal macrosomiafetal programminggestational weight gain
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 8 , Issue 5: Themed Issue: Australian Perspectives: Outcomes from the 2016 ANZ , October 2017 , pp. 575 - 583
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2017 

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Footnotes

a

Present address: Maternal Fetal Medicine, Carolinas Medical Center, Charlotte, NC 28204, USA.

b

Present address: Children’s Hospital of Philadelphia, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA 19104, USA.

Presented at meeting: The 61st Annual Society for Gynecological Investigation Scientific Meeting, Florence, Italy, March 2014.

†

These authors contributed equally.

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