Abstract
Polycystic ovarian syndrome (PCOS) is a multi-factorial gynecological endocrine disorder. It affects fertility in women and also predisposes to insulin resistance, type 2 diabetes mellitus, obesity etc. Earlier, significance of autophagy has been explored in PCOS-related metabolic disorders and during normal folliculogenesis. Increasing evidences reveal connection of autophagy with chronic inflammatory behaviour, an associated phenomena in polycystic ovaries. However, understanding of the association of autophagy with PCOS is still obscure. This study reveals that increased autophagy in mifepristone (RU486) treated KK-1 cells and in vivo PCO rat model is characterized by upregulated Androgen Receptor (AR) expression and downregulated PCO biomarker aromatase. The prevalence of autophagy has been observed to be concomitant with increased expression of two autophagic markers Beclin1 and MAP-LC3-II while the autophagy substrate p62/SQSTM1 was downregulated. Immunohistochemical staining revealed increased localization of MAP-LC3 in the compacted granulosa layers of the follicular cysts in the PCO model. The PCO rat models also demonstrated augmented levels of p65, the active subunit of NF-κB, which acts as a transcriptional regulator of several pro-inflammatory factors. NF-κB repressor and anti-inflammatory herbal drug thymoquinone, known to alleviate PCO condition, downregulated autophagy modules substantially. Pre-treatment with thymoquinone upregulated aromatase, reduced AR levels and decreased autophagic markers as well as p65 levels, simulating super-ovulated condition. In conclusion, the anti-inflammatory phytochemical thymoquinone alleviated PCO condition.
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