Research questionDoes cholesterol metabolism differ in patients with diminished ovarian reserve (DOR) compared to patients with normal ovarian reserve (NOR)? DesignThe current research included 72 women with NOR and 86 women with DOR. Data on the cholesterol metabolism in granulosa cells of these women were analysed. ResultsOn the day of human chorionic gonadotrophin injection, serum oestradiol and progesterone in the DOR group were significantly lower than in the control group (P < 0.001). There were no significant differences in serum concentrations of total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein between the NOR and DOR groups. The cholesterol-regulated gene SCAP in granulosa cells from women with DOR was down-regulated (P = 0.024). Cholesterol synthesis and transport genes (e.g. IDI1, FDFT1, CYP51A1, SRB1 and STARD1) were also significantly decreased (P = 0.026, P = 0.044, P = 0.049, P = 0.004 and P < 0.001, respectively). In granulosa cells of patients with DOR, cholesterol-related substances such as coprostanone, 11A-acetoxyprogesterone and 17α-hydroxyprogesterone were significantly reduced (P = 0.0008, P = 0.0269, P = 0.0337, respectively). CYP19A1, a key steroidogenesis gene, was significantly reduced (P = 0.009). 17α-hydroxyprogesterone and oestradiol decreased (P = 0.004 and P = 0.039, respectively). ConclusionDecreased cholesterol metabolism affecting steroid hormone synthesis in granulosa cells might be a possible mechanism for DOR.
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