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Publication
Maternal Hyperglycemia Induces Changes in Gene Expression and Morphology in
Mouse Placentas.
Authors Eckmann M, Sheng Q, Baldwin H S, Lister RL
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Gynecology & reproductive health
Year 2021
Date Published
Volume : Pages 5 : Not Specified
PubMed Reference 34250501
Abstract Pregestational diabetes complicates one million pregnancies in the United States
and is associated with placental dysfunction. Placental dysfunction can manifest
as stillbirth, spontaneous abortions, fetal growth restriction, and preeclampsia
in the mother. However, the underlying mechanisms of placental dysfunction are
not well understood., We hypothesize that maternal hyperglycemia disrupts
cellular processes important for normal vascular development and function.,
Hyperglycemia, defined as a non-fasting glucose concentration of >250 mg/dL was
induced in eight-week-old female CD1 mice by injecting a one-time
intraperitoneal dose of 150mg/kg streptozotocin. Control mice received an equal
volume of normal saline. Hyperglycemic and control females were mated with CD-1
males. At Embryonic Day 17.5, the pregnant mice were euthanized. Sixty-eight
placentas were harvested from the six euglycemic dams and twenty-six placentas
were harvested from three hyperglycemic dams. RNA was extracted from homogenized
placental tissue (N=12/group; 2-4 placentas per litter of each group). Total RNA
was prepared and sequenced. Differentially expressed genes that were >2-fold
change was considered significant. Placentas (9-20/group) were fixed in paraffin
wax and sectioned at 6 µm. Cross-sectional areas of placental zones were
evaluated using slides stained for hematoxylin and eosin, glycogen, collagen,
proliferation and apoptosis. Quantification of staining intensity and percent
positive nuclei was done using Leica Image Hub Data software. Data were compared
between the control and experimental group using t-tests. Values of p < 0.05
were considered to be statistically significant., The average maternal blood
glucose concentrations for control and diabetic dams were 112+/-24 and 473+/-47
respectively (p<0.0001). A higher rate of resorptions was noted in the
hyperglycemia exposed placentas compared to euglycemic exposed placentas (24% vs
7%; p=0.04). A total of 24 RNA libraries (12/group) were prepared. Placentas
from hyperglycemic pregnancies exhibited 1374 differentially expressed genes
(DEGs). The 10 most significantly differentially expressed genes are Filip 1,
Prom 2, Fam 78a, Pde4d, Pou3f1, Kcnk5, Dusp4, Cxcr4, Slc6a4 and D430019H16Rik.
Their corresponding biologic functions are related to chemotaxis, ossification,
cellular and vascular development. Histologically, we found that hyperglycemia
exposed placentas demonstrated increased proliferation, apoptosis, and glycogen
content and decreased collagen deposition., There was a higher rate of
resorptions in the pregnancies of hyperglycemic dams. Pregestational diabetes
resulted in significant changes in placental morphology, including increased
glycogen content in the spongiotrophoblast, decreased collagen deposition,
increased apoptosis and proliferation in the junction zone. Maternal diabetes
causes widespread disruption in multiple cellular processes important for normal
vascular development and sets the platform for placenta dysfunction.




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