carbocyanines and Polycystic-Ovary-Syndrome

Mitochondrial injury in granulosa cells (GCs) is associated with the pathophysiological mechanism of polycystic ovary syndrome (PCOS). Melatonin reduces the mitochondrial injury by enhancing SIRT1 (NAD-dependent deacetylase sirtuin-1), while the mechanism remains unclear. Mitochondrial membrane potential is a universal selective indicator of mitochondrial function. In this study, mitochondrial swelling and membrane defect mitochondria in granulosa cells were observed from PCOS patients and DHT-induced PCOS-like mice, and the cytochrome C level in the cytoplasm and the expression of BAX (BCL2-associated X protein) in mitochondria were significantly increased in GCs, with p-Akt decreased, showing mitochondrial membrane was damaged in GCs of PCOS. Melatonin treatment decreased mitochondrial permeability transition pore (mPTP) opening and increased the JC-1 (5,5',6,6'-tetrachloro1,1',3,3'-tetramethylbenzimidazolylcarbocyanine iodide) aggregate/monomer ratio in the live KGN cells treated with DHT, indicating melatonin mediates mPTP to increase mitochondrial membrane potential. Furthermore, we found melatonin decreased the levels of cytochrome C and BAX in DHT-induced PCOS mice. PDK1/Akt played an essential role in improving the mitochondrial membrane function, and melatonin treatment increased p-PDK 1 and p-Akt in vivo and in vitro. The SIRT1 was also increased with melatonin treatment, while knocking down SIRT1 mRNA inhibiting the protective effect of melatonin to activate PDK1/Akt. In conclusion, melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS.

Topics: 3-Phosphoinositide-Dependent Protein Kinases; Adult; Animals; bcl-2-Associated X Protein; Benzimidazoles; Carbocyanines; Cytochromes c; Cytoplasm; Female; Gene Knockdown Techniques; Granulosa Cells; Humans; Melatonin; Membrane Potential, Mitochondrial; Mice; Mitochondria; Mitochondrial Membranes; Mitochondrial Permeability Transition Pore; Polycystic Ovary Syndrome; Proto-Oncogene Proteins c-akt; Sirtuin 1

To explore the gene which might influence endometrium receptivity during the implantation window time in normal women and patients with polycystic ovary syndrome (PCOS).. Transvaginal ultrasound were performed and serum estrogen and progestogen levels were measured in all women to monitor the exact time of ovulation. Endometrium biopsy was done in normal women and PCOS patients during implantation window time. Sixteen women were enrolled in this study, in which seven were normal women, and nine were PCOS patients. cDNA extraction was performed, matrix metalloproteinase 26 (MMP-26) primers were synthesized and real time fluorescent quantitative PCR was conducted using beta-actin gene as endogenous control.. The ratios of MMP-26 were 0.31, 0.11 and 0.05 in 3 patients with PCOS by real time fluorescent quantitative PCR, obviously decreased during implantation time compared with the normal women.. Our data suggest a lower expression of MMP-26 in implantation window time in patients with PCOS than in normal patients. This might indicate a declined capability of endometrium receptivity in implantation window time in patients with PCOS.

Topics: Adult; Carbocyanines; DNA, Complementary; Embryo Implantation; Endometrium; Female; Gene Expression Regulation, Enzymologic; Humans; Matrix Metalloproteinases, Secreted; Menstrual Cycle; Polycystic Ovary Syndrome; Reverse Transcriptase Polymerase Chain Reaction; Time Factors