Abstract: Objective To study the mechanism of high glucose-induced apoptosis of human villous trophoblasts HTR- 8/SVneo. Methods Human villous trophoblasts HTR-8/SVneo were cultured in vitro and divided into the blank control group, the high glucose group, the negative control group (NC), the phosphatase and tensin homology deleted on chromosome ten (PTEN) -siRNA group (inhibition of PTEN expression) and the mammalian target of rapamycin (mTOR) pathway inhibitor group (GDC-0349 group). Methyl thiazolyl tetrazolium (MTT) assay and flow cytometry were used to detect the proliferation of HTR-8/SVneo cells and the apoptosis of HTR-8/SVneo cells, respectively. The expression of apoptosis related proteins and proteins related to PTEN/mTOR pathway were detected by Western blot assay. Results Compared with the blank control group, HTR-8/SVneo cell proliferation inhibition rate, apoptosis rate and Bcl-2 related X protein (Bax), cleaved caspase-3 and PTEN protein expression levels were significantly increased in the high glucose group (P＜0.05), while the expression levels of B-cell lymphoma-2 (Bcl-2), phosphorylation phosphatidylinositol-3-kinase (p-PI3K)/PI3K, phosphorylation protein kinase B (p-AKT)/AKT and phosphorylation mTOR (p-mTOR)/mTOR protein were significantly decreased (P＜0.05). Compared with the high glucose group and the NC group, the HTR-8/SVneo cell proliferation inhibition rate, apoptosis rate, Bax, cleaved caspase-3 and PTEN protein expression levels were significantly decreased in the PTEN-siRNA group (P＜0.05), while the expression levels of Bcl-2, p-PI3K/PI3K, p-AKT/AKT and p-mTOR/mTOR protein were significantly increased (P＜0.05). Compared with the PTEN-siRNA group, the proliferation inhibition rate, apoptosis rate and the protein expression levels of Bax, cleaved caspase-3 were significantly increased in the GDC-0349 group (P＜0.05), while the expression levels of Bcl-2, p-PI3K/PI3K, p-AKT/AKT and p-mTOR/mTOR protein were significantly decreased (P＜0.05). Conclusion High glucose can inhibit the growth and induce apoptosis of human villous trophoblasts HTR-8/SVneo, which may be achieved by up-regulating the expression of PTEN and inhibiting the activation of PI3K/AKT/mTOR pathway.

Key words: TOR serine-threonine kinases, trophoblasts, apoptosis, PTEN phosphohydrolase, phosphatidylinositol 3-kinase, high glucose, human villous trophoblasts HTR-8/SVneo