Menopause is the most important sign of aging in women, and the ovary is the organ most sensitive to aging. Quercetin is a potential antioxidant and free radical scavenger that is widely found in fruits, vegetables, and leaves. However, the effect of quercetin on ovarian aging has not been elucidated, and the mechanism underlying its antioxidative effect remains unclear. The purpose of the current study was to investigate whether quercetin protects ovarian function by decreasing oxidative stress. In an in vivo experiment, female menopausal rats (12 months old) were intragastrically administered quercetin at three doses (12.5 mg/kg, 25 mg/kg, and 50 mg/kg) for 90 days, and the estrous cycles were determined by vaginal smearing. In an in vitro experiment, rat primary ovarian granulosa cells were cultured and treated with H2O2 (400 μM) alone or H2O2 plus quercetin at 5 μM, 20 μM, or 50 μM. The levels of the hormones estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were detected by radioimmunoassay. The serum levels of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-PX) and glutathione S-transferase (GST) were examined. The expression levels of the oxidative stress-related genes SOD-1, catalase (CAT) and glutathione synthetase (GSS) in the ovaries and ovarian granulosa cells were detected by Western blot. The in vivo results demonstrated that quercetin had no effects on ovarian morphology, hormone secretion, or the estrous cycle in menopausal rats. Although no significant changes were detected in the serum levels of T-AOC, SOD, GSH, GSH-PX, and GST between the quercetin and control groups, the mRNA and protein expression levels of the oxidative stress-related genes SOD-1, CAT and GSS in menopausal rat ovaries were increased by low-dose quercetin. Moreover, the in vitro results demonstrated that quercetin significantly rescued the decrease in cell viability by H2О2-induced oxidative stress and enhanced the H2O2-induced decrease in expression of oxidative stress-related proteins. Together, the results of this study indicated that quercetin increased the antioxidant capacity of the ovary by upregulating the expression of some oxidative stress-related genes both in vivo and in vitro.

Glucose transporter isoform-3 (GLUT3), one of the primary placental facilitative glucose transporters responsible for basal glucose transport, has a crucial role in glucose transport and fetal growth during early pregnancy. A GLUT3 mutation in mice has been reported to cause loss of early pregnancy or late-gestational fetal growth restriction. However, the underlying mechanisms that regulate the placental GLUT3 transporter in humans are largely unknown. In the present study, we used the JEG-3 human choriocarcinoma cell line, which resembles a first trimester placental model, to study the role of the mammalian target of rapamycin complex 1 (mTORC1) in the regulation of placental GLUT3. We combined rapamycin treatment and small interfering (si) RNA-mediated silencing approaches with mRNA and protein expression/localization studies to investigate the alteration of GLUT3 expression and localization following mTORC1 inhibition in JEG-3 trophoblasts. Inhibition of mTORC1 signaling by silencing raptor decreased GLUT3 mRNA expression (−41%) and protein expression (−50%). Similar effects were obtained in cells in which mTORC1 was inhibited by rapamycin. Immunofluorescence analysis revealed that GLUT3 expression was markedly reduced in the cell surface and cytoplasm of JEG-3 cells in response to mTORC1 silencing. Because placental mTORC1 activity and GLUT3 expression are decreased in human intrauterine growth restriction, our data suggested one possible mechanism for the abnormal fetal growth in this pregnancy complication.