ABSTRACT
BACKGROUND: Paraoxonase-3 (PON3), as a high density lipoprotein (HDL)-associated lactonase, is capable of preventing the oxidative modification of low density lipoprotein (LDL). PON3 activity in follicular fluid (FF) is three times more than its activity in serum. However, the detailed role of PON3 in women's fertility remains unknown. The aim of this study was to investigate the correlation between PON3 activity in the FF of women undergoing assisted reproductive technique (ART), in vitro fertilization (IVF), or intra-cytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: This cross-sectional study consisted of 50 women from couples with male factor infertility (MFI) or with female factor infertility (FFI). The FF samples were obtained during the ART intervention. PON3 activity, HDL cholesterol (HDL C), total antioxidant status (TAS) and the level of malondialdehyde (MDA) were determined. The morphology of the embryo was determined using embryo cell number (ECN) and embryo fragmentation score (EFS). In addition, fertilization rate (FR) was used an oocyte fertilization index. RESULTS: Of 50 women, 20 women belonged to FFI group and the remaining 30 women belonged to MFI group. PON3 activity in FF of women in FFI group was significantly lower (p<0.05) in comparison with corresponding value in MFI group. The value of PON3 activity/MDA in the FFI group was lower than that in MFI group. Moreover, MDA level in the FF of FFI group was significantly higher (p<0.05) than its concentration in MFI group. Meanwhile, no significant difference was found in HDL-C concentration and TAS of both groups. No significant correlation was observed between the ECN and FF biochemical parameters. There was also a negative correlation between FR and MDA (r=-0.42, p=0.02), whereas a positive relation between FR with PON3 activity (r=0.59, p=0.004), HDL-C (r=0.35, p=0.04) and PON3/MDA (r=0.59, p=0.001). CONCLUSION: According to the results of this study, PON3 activity level as a key component of antioxidant system in FF may directly be associated with the success rate of ART and fertilization rate in women.
ABSTRACT
PURPOSE: Stearoyl-CoA desaturase 1 (SCD1) is a novel therapeutic target in various malignancies, including breast cancer. The present study was designed to investigate the effect of the pharmacologic inhibition of SCD1 on fatty acid composition in tissue explant cultures of human breast cancer and to compare these effects with those in adjacent nonneoplastic breast tissue. METHODS: Paired samples of tumor and adjacent noncancerous tissue were isolated from 12 patients with infiltrating ductal breast cancer. Samples were explant cultured in vitro, exposed to the highly selective SCD1 inhibitor CAY10566, and examined for fatty acid composition by gas liquid chromatography. The cytotoxic and antigrowth effects were evaluated by quantification of lactate dehydrogenase release and by sulforhodamine B (SRB) measurement, respectively. RESULTS: Breast cancer tissue samples were found to have higher levels of monounsaturated fatty acids (MUFA) (p<0.001) and arachidonic acid (20:4n-6, p<0.001) and a lower level of linoleic acid (18:2n-6, p=0.02) than the normal-appearing breast tissues. While exhibiting no evident cytotoxicity, treatment with the SCD1 inhibitor, CAY10566 (0.1-1 microM), for 48 hours significantly increased 18:2n-6 levels in both the tumor and adjacent normal-appearing tissue (approximately 1.2 fold, p<0.05). However, the breast cancer tissue samples showed significant increases in the levels of MUFA and 20:4n-6 compared to the normal-appearing breast tissues (p<0.05). The SRB growth assay revealed a higher rate of inhibition with the SCD1 inhibitor in breast cancer tissues than in normal-appearing tissues (p<0.01, 41% vs. 29%). The SCD1 inhibitor also elevated saturated fatty acid (1.46-fold, p=0.001) levels only in the tumor tissue explant. CONCLUSION: The fatty acid composition and response to SCD1 inhibition differed between the explant cultures from breast cancer and the adjacent normal-appearing tissue. Altered fatty acid composition induced by SCD1 inhibition may also, in addition to Delta9 desaturation, modulate other reactions in de novo fatty acid synthesis and lipogenesis, and subsequently affect the overall survival and progression of breast cancer.
