Inhibition of oocyte maturation by follicular extracellular vesicles of non-hyperandrogenic PCOS patients requiring IVF


 
 
 Polycystic ovarian syndrome (PCOS) is one of the most common diseases that contribute to subfertility. Recent evidence showed that oocytes of women with PCOS matured in vitro away from the follicular fluid presented better potentials, whereas the reason remained unclear.
 
 
 
 To investigate whether follicular extracellular vesicles (EVs) of PCOS patients interfere with the quality of oocytes.
 
 
 
 Follicular EVs of women with PCOS (PCOS-EVs) and control women (CTRL-EVs) were isolated and determined using western blotting, nanoparticle tracking analysis, and transmission electron microscopy. The two types of EVs were co-cultured with murine germinal vesicle oocytes, respectively. Fluorescence labeled EVs were used to visualize internalization by oocytes. After co-culture, oocyte maturation rates were calculated. Mitochondria distribution and reactive oxygen species (ROS) level were detected in the different groups. Spindle morphology was evaluated using immunofluorescence. Moreover, the expression of catalase (CAT), glutathione synthetase (GSS), and superoxide dismutase (SOD) was determined in the oocytes.
 
 
 
 Both PCOS-EVs and CTRL-EVs are bilayered vesicles, approximately 100-150 nm in size, and enriched in EV-associating protein markers. EVs were internalized by oocytes within one hour. Oocyte maturation rate decreased significantly in the PCOS-EV group compared with the CTRL-EV group; whereas the abnormal mitochondria distribution rate and abnormal spindle rate were significantly increased in the PCOS-EV group. Moreover, PCOS-EVs increased the ROS level and the expression of CAT, GSS, and SOD in the oocytes.
 
 
 
 PCOS-EVs interfered with oocyte mitochondria and spindles and inhibited oocyte maturation. Moreover, oxidative stress induced by PCOS-EVs might be a potential cause.
