Circular DDX10 is associated with ovarian function and assisted reproductive technology outcomes through modulating the proliferation and steroidogenesis of granulosa cells

circRNAs are present in human ovarian tissue, but how they regulate ovarian function remains unknown. In the current study, we investigated the levels of circRNAs in granulosa cells (GCs) derived from human follicular fluid, explored their correlation with female ovarian reserve function and clinical outcomes of assisted reproduction technique (ART), and investigated their effects on the biological functions of GC cell lines (COV434) in vitro. We identified that the levels of circDDX10 in GCs decreased gradually with aging (P < 0.01) and was positively correlated with AMH (r = 0.45, P < 0.01) and AFC (r = 0.32, P 0.01), but not with FSH and estradiol (P 0.05). Additionally, circDDX10 was related to the number of oocytes obtained, and good quality embryo rates. Silencing circDDX10 in GCs could markedly up-regulate the expression of apoptosis-related factors, reduce cell proliferation activity, inhibit the expression of steroid hormone synthesis-related factors, and prohibit the synthesis of estradiol. On the contrary, over-expression of circDDX10 had the opposite effect. circDDX10 is expected to become a novel biomarker for predicting the outcomes of ART, and may participate in the regulation of ovarian function by affecting the proliferation and apoptosis of GCs and steroid hormone synthesis.

Automated summary

The study found that circDDX10 levels in GCs decrease with age and are positively correlated with AMH and AFC. circDDX10 is also related to the number of obtained oocytes and rates of good quality embryos.