This study was designed to investigate the protective effect of curcumin againstd-galactose (d-gal)-induced premature ovarian failure (POF) in mice. A mouse POF model was induced by subcutaneous injection ofd-gal (200 mg/kg/day) daily for 42 days. Mice in the curcumin group received bothd-gal treatment and intraperitoneal injection of curcumin (100 mg/kg/day) for 42 days. Ovarian function, oxidative stress and apoptosis were evaluated. The P, E2 and SOD levels were higher, and the FSH, LH and MDA levels were significantly lower in the curcumin group than those in thed-gal group. The proportion of primordial follicles was also significantly higher in the curcumin group than that in thed-gal group. In addition, curcumin treatment afterd-gal administration resulted in significantly lowerSod2,Cat, 8-OhdG, 4-HNE, NTY and senescence-associated protein P16 expression levels, higherAmhexpression levels and less apoptosis in granulosa cells than was observed in thed-gal group. Moreover, the p-Akt, Nrf2 and HO-1 protein expression levels were significantly higher and the apoptosis-related cleaved caspase-3 and -9 protein expression levels were markedly lower in the curcumin group than in thed-gal group. In conclusion, curcumin effectively inhibitedd-gal-induced oxidative stress, apoptosis and ovarian injury via a mechanism involving the Nrf2/HO-1 and PI3K/Akt signaling pathways, suggesting that curcumin is a potential protective agent against POF.

Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy, and has important health implications for mother and child. Changes in the fetoplacental vessels may predict those in the vasculature of the developing fetus, as these have been implicated in the pathogenesis of human GDM. This study aimed to determine the differences in the localization and expression level of VEGFA and VEGFR2 between placentas of women with GDM and placentas of normal pregnancies, which is the first step in elucidating the possible roles of VEGFA and VEGFR2 in the altered uteroplacental function resulting from maternal hyperglycaemia and ultimately in the manifestation of GDM. The expressions of VEGFA and VEGFR2 mRNA and protein in 20 samples from each group were analyzed by real-time PCR, immunohistochemistry and Western blot. The placental blood barrier and angiogenesis were observed by the transmission electron microscopy (TEM) in10 GDM samples and ten controls. The expression levels of VEGFA and VEGFR2 mRNA and protein were significantly decreased in the GDM group (P < 0.05 or 0.01). Immunohistochemical analysis showed the reduced expression of VEGFA and VEGFR2 protein in GDM-affected placental tissues, and the degenerative alterations of the terminal villi vascular. The expressions of VEGFA and VEGFR-2 mRNAs and protein were reduced in GDM-affected placental tissues, suggesting that maternal GDM affects the pathophysiological function of placentas.

Objectives. Gestational diabetes mellitus (GDM) leads to an abnormal placental environment which may cause some structural alterations of placenta and affect placental development and function. In this study, the ultrastructural appearances of term placentas from women with GDM and normal pregnancy were meticulously compared.Materials and Methods. The placenta tissues of term birth from 10 women with GDM and 10 women with normal pregnancy were applied with the signed informed consent. The morphology of fetomaternal interface of placenta was examined using light microscopy (LM) and transmission electron microscopy (TEM).Results. On LM, the following morphological changes in villous tissues were found in the GDM placentas when compared with the control placentas: edematous stroma, apparent increase in the number of syncytial knots, and perivillous fibrin deposition. On TEM, the distinct ultrastructural alterations indicating the degeneration of terminal villi were found in the GDM placentas as follows: thickening of the basal membrane (BM) of vasculosyncytial membrane (VSM) and the VSM itself, significantly fewer or even absent syncytiotrophoblastic microvilli, swollen or completely destroyed mitochondria and endoplasmic reticulum, and syncytiotrophoblasts with multiple vacuoles.Conclusion. Ultrastructural differences exist between GDM and control placentas. The differences of placenta ultrastructure are likely responsible for the impairment of placental barrier and function in GDM.

If fertilization does not occur for a prolonged period in vivo or in vitro, the postovulatory oocytes will deteriorate, which called the postovulatory aging. This process disrupts the developmental competence. In the present study, we showed that the reactive oxygen species (ROS) was accumulated in oocytes during the postovulatory aging. ROS inhibited Sirt1 expression, and then increased oxidative stress by downregulating the intracellular Sirt1-FOXO3a-SOD2 axis. Moreover, the inhibited Sirt1 expression was related to the decreased mitochondrial function and the lowered level of autophagy. The mitochondrial-related apoptosis was increased by inhibiting the AKT and ERK1/2 pathways, due to the accumulation of ROS in the postovulatory oocytes. The mitochondrial pyruvate dehydrogenase kinase-4 (PDK4) can reduce ROS by inhibiting the tricarboxylic acid (TAC) cycle. We found that PDK4 was significantly decreased in the postovulatory aging oocytes. Putrescine, one of the abundant biogenic amines, ameliorated the effects of ROS and therefore improved the quality of the postovulatory aging oocytes by increasing the expression of PDK4. When PDK4 was downregulated using siRNAs, the effects of putrescine were significantly receded. We concluded that putrescine delayed the aging process of postovulatory oocytes by upregulating PDK4 expression and improving mitochondrial activity.

Although many nanomaterials are being used in academia, industry and daily life, there is little understanding about the effects of nanoparticles on the reproductive health of vertebral animals, including human beings. An experimental study was therefore performed here to explore the effect of calcium phosphate nanoparticles on both steroid hormone production and apoptosis in human ovarian granulosa cells. Calcium phosphate nanoparticles uptaking was evaluated by transmission electron microscopy (TEM). The cell cycle was assessed with propidium iodide-stained cells (distribution of cells in G0/G1, S, and G2/M phases) by flow cytometry. The pattern of cell death (necrosis and apoptosis) was analyzed by flow cytometry with annexin V-FITC/PI staining. The expression of mRNAs encoding P450scc, P450arom and StAR were determined by RT-PCR. Progesterone and estradiol levels were measured by radioimmunoassay. TEM results confirmed that calcium phosphate nanoparticles could enter into granulosa cells, and distributed in the membranate compartments, including lysosome and mitochondria and intracellular vesicles. The increased percentage of cells in S phase when cultured with nanoparticles indicated that there was an arrest at the checkpoint from phase S-to-G2/M (from 6.28 +/- 1.55% to 11.18 +/- 1.73%, p < 0.05). The increased ratio of S/(G2/M) implied the inhibition of DNA synthesis and/or impairment in the transition of the S progression stage. The apoptosis rate of normal granulosa cells was 7.83 +/- 2.67%, the apoptotic rate increased to 16.53 +/- 5.56% (P < 0.05) after the cells were treated with 100 microM calcium phosphate nanoparticles for 48 hours. Treatment with calcium phosphate nanoparticles at concentrations of 10-100 microM didn't significantly change either the progesterone or estradiol levels in culture fluid, and the expression levels of mRNAs encoding P450scc, P450arom and StAR after 48 h and 72 h period of treatment. Calcium phosphate nanoparticles interfered with cell cycle of cultured human ovarian granulosa cells thus increasing cell apoptosis. This pilot study suggested that effects of nanoparticles on ovarian function should be extensively investigated.