Changes in Placental
Adipocytokine Gene Expression Associated with Gestational
Diabetes Mellitus
M. MELLER1, C. QIU1, S.
VADACHKORIA1, D. F. ABETEW1, D. A. LUTHY1,2,
M. A. WILLIAMS1,3
1Center for Perinatal Studies, Swedish Medical
Center, Seattle, WA, 2Obstetrix Medical Group,
Seattle, WA, and 3Department of Epidemiology,
University of Washington School of Public Health and Community
Medicine, Seattle, WA, USA.
Received date September 27, 2005
Accepted date November 21, 2005
On-line available December 12, 2005
Summary
Leptin and adiponectin, two adipocytokines, may work together in
regulating energy homeostasis and insulin action. Leptin gene
expression has been investigated in term placental tissue
complicated by gestational diabetes mellitus (GDM), but never in
conjunction with all isoforms of the leptin receptor (LEPR A-D),
or with adiponectin receptors (ADIPOR1 and 2). In this study we
examined the association between changes in expression of these
genes in placental tissue and GDM risk. We assessed placental
gene expression of leptin, LEPR A-D and ADIPOR1 and 2 by real
time PCR using mRNA from maternal and fetal biopsies. Tissues
were collected from uncomplicated pregnancies (n=28) and those
complicated by GDM (n=19). Gene expression was normalized to
three endogenous housekeeping genes. Relative gene expression
values were reported as fold change between groups. Adiponectin
gene expression was out of the sensitive range of our assay.
There were increases in leptin mRNA expression in GDM cases
compared with controls for maternal-side (p=0.06), and
fetal-side (p=0.09) placental biopsies. No significant changes
were seen in GDM cases compared with controls in LEPR A-D or
ADIPOR1 and 2. mRNA derived from maternal-side tissue was
positively correlated with tissue from the fetal side for all
genes studied (all p<0.01). Finally, we noted that absence or
presence of GDM was a major factor in leptin mRNA expression
after adjusting for maternal age, mode of delivery, parity and
smoking status. In conclusion, increases in leptin mRNA
expression in term placenta, but not that of its receptors, are
associated with the diagnosis of GDM. Changes seen in the
ligand, but not the receptor, of the leptin pathway in
GDM-complicated pregnancies may also apply to the adiponectin
pathway, as the ADIPOR1 and 2 mRNAs do not change with GDM
diagnosis.
Key words
Gestational diabetes mellitus (GDM) • Leptin • Adiponectin •
Placenta • Gene expression
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