The effect of platelet-rich plasma extracellular vesicles (PRP-EVs) on the expression of BECN1, CYP19a1, and BMP6 as critical genes related to autophagy and steroidogenesis in ovarian granulosa cells of polycystic ovarian syndrome (PCOS) mouse model.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is the most common endocrine condition in which aberrant expression of androgens leads to disrupted steroidogenesis, increased apoptosis, as well as autophagy in granulosa cells (GCs) and impaired ovulation. Here, we evaluated the therapeutic capacity of extracellular vesicles derived from platelet-rich plasma (PRP-EVs) on the expression of genes related to autophagy and steroidogenesis in ovarian GCs of PCOS mouse model.

METHODS: In this experimental study, 40 female NMRI mice were classified into four groups, including control (untreated) and experimental groups 2, 3, and 4 (n = 8). The experimental group of 2 was considered as PCOS mice. PCOS was induced using a single subcutaneous injection of estradiol valerate (4 mg/kg). In the experimental groups of 3 and 4, (60 days after PCOS induction) PRP-EVs were injected intraperitoneally at doses of 25 and 50 µg/kg body weight for two consecutive weeks. For this purpose, PRP-EVs were isolated from eight NMRI mice and characterized with DLS, as well as assessment the CD63 EVs marker using flow cytometry. The effect of PRP-EVs on the PCOS ovaries was evaluated by analyzing serum hormone levels and histological analysis. Finally, assessment of the steroidogenic and autophagic gene expression was performed in isolated ovarian GCs using quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS: According to the hormonal analysis, PCOS mice had a decreased FSH/LH ratio compared to the control group. Histological data also showed more cystic follicles (CF) and more occasional healthy follicles in PCOS mice. Furthermore, in PCOS-induced mice, attenuation of CYP19a1, as well as an increment in BECN1 and BMP6, was observed in the transcriptional levels of isolated GCs. In contrast, the FSH/LH ratio and ovarian structures were revitalized by PRP-EVs treatment (50 µg/kg body weight). In addition, gene expression analysis exhibited CYP19a1 up-regulation, as well as BECN1 and BMP6 down-regulation in ovarian GCs under exposure to an optimum dose of PRP-EVs.

CONCLUSION: Overall, our study suggests that PRP-EVs can be suggested as a promising biopharmaceutical source for PCOS conditions as a novel therapeutic option. Despite this advance, purifying EVs, quantifying EVs by particle size, providing safety, and determining fertility outcomes hinder the clinical application of PRP-EVs.