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Int J Clin Exp Pathol 2013;6(4):650-659

Original Article
Gestational diabetes induces chronic hypoxia stress and excessive in-flammatory
response in murine placenta

Hua-Ping Li, Xuan Chen, Ming-Qing Li

Department of Gynecology & Obstetrics, the 6th People’s Hospital affiliated to Shanghai Jiaotong University, Shanghai 6th People’s Hospital,
Shanghai 200233, China; Soochow University Medical College, Suzhou 215123, China; Laboratory for Reproductive Immunology, Hospital and
Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, 200011, China. These authors contribute
equally to this work.

Received January 13, 2013; Accepted February 22, 2013; Epub March 15, 2013; Published April 1, 2013

Abstract: Metabolic impairments in maternal obesity and gestational diabetes mellitus (GDM) induce an abnormal environment in peripheral
blood and cause vascular structure alterations which affect the placental development and function. A GDM model was developed using
C57BL/6J female mice fed with high fat food (HF) (40% energy from fat) and a control group with control food (CF) (14% energy from fat) for 14
weeks before mating and throughout the gestation period. A subset of dams was sacrificed at gestational day (GD) 18.5 to evaluate the fetal
and placental development. HF-fed dams exhibited significant increase in the maternal weight gain and homeostasis model assessment for
insulin resistance index (HOMA-IR), impaired insulin secretion of glucose stimulus and glucose clearance of insulin stimulus before
pregnancy; in addition, they also had the increase in the fetal and placental weight. HF-fed dams at GD 18.5 showed the high level of circulating
maternal inflammation factors and were associated with increased oxidative stress and hypoxia in the labyrinth, abnormal vascular
development with a high level of hypoxia inducible factor-1α (HIF-1α) and VEGF-A expression, but without a parallel increase in CD31 level;
were induced an exaggerated inflammatory response in placental vascular endothelial cell. Our findings show that GDM induces more
maternal weight gain and fetus weight, with abnormal maternal circulating metabolic and inflammation factors, and forms a placental hypoxia
environment and impacts the placental vascular development. Our findings indicate that gestational diabetes induce excessive chronic hypoxia
stress and inflammatory response in placentas which may contribute mechanisms to the high risks of perinatal complications of obesity and
GDM mothers. (IJCEP1301026).

Keywords: High fat diet, obesity, GDM, placenta, oxidative stress, hypoxia, inflammation factor

Address correspondence to: Dr. Hua-Ping Li, Department of Gynecology & Obstetrics, the 6th People’s Hospital affiliated to Shanghai
Jiaotong University, Shanghai 6th People’s Hospital, 600 Yishan Road, Shanghai 200233, China. Tel: 86-21-64369181; E-mail: hpli819@sohu.