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Chun-Yi Guan,1,2,* Shi Tian,3,* Jing-Li Cao,1,2 Xue-Qin Wang,1,2 Xu Ma,1,2 Hong-Fei Xia1,2 1Reproductive and Genetic Center of National Research Institute for Family Planning, Beijing 100081, People’s Republic of China; 2Graduate School, Peking Union Medical College, Beijing Province 100005, People’s Republic of China; 3Haidian Maternal & Child Health Hospital, Beijing 100080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xu Ma; Hong-Fei XiaReproductive and Genetic Center of National Research Institute for Family Planning, Beijing 100081, People’s Republic of ChinaTel +86-10-62178932Fax +86-10-62179059Email xuma_genetics@163.com; hongfeixia@126.comPurpose: This study aimed to investigate the role of miR-21 expression in the reduction of placental function in GDM patients.Materials and Methods: qRT-PCR was used to detect the differential expression of miR-21 in the serum of gestational diabetes mellitus (GDM) and normal pregnant women, and to verify the functional target gene PPAR-α of miR-21 by double fluorescence experiments. Cellular experiments were performed to verify the effect of PPAR-α on cell function.Results: miR-21 is down-regulated in the serum and placenta of GDM patients compared to normal pregnant women. In the case of insulin resistance, miR-21-5p knockdown promoted glucose uptake, but no significant effect was found under physiological condition. Functional studies have shown that reduced PPAR-α expression can restore miR-21 knockdown-mediated cell growth and metastasis inhibition. Additionally, decreased expression of miR-21 but increased expression of -PPAR-α was observed in patients with GDM and GDM rats.Conclusion: The expression of the placental miR-21-5p, which inhibits cell growth and infiltration by up-regulating PPAR-α, is downregulated in pregnant GDM patients, which in turn may affect the placental function.Keywords: gestational diabetes mellitus, miRNA-21, insulin resistance, PPAR-α