MicroRNA profiling reveals effects of Erzhi Tiangui granules on kidney deficiency diminished ovarian reserve: A randomized trial

Background: Diminished ovarian reserve (DOR) is a danger signal of reduced fertility. The clinical incidence is increasing yearly, exhibiting a gradual low-age trend. Traditional Chinese medicine theory suggests that kidney deficiency is the basic pathogenesis. Erzhi Tiangui granules (ETG), a kidney-tonifying prescription, have been clinically shown to improve ovarian reserve function. The purpose of this study was to investigate the microRNA (miRNA) markers of kidney deficiency DOR and the potential mechanism of ETG on in vitro fertilization outcomes in DOR patients. Methods: Experiment 1: Granulosa cells from 5 normal ovarian reserves and 5 kidney deficiency DOR patients were subjected to miRNA sequencing. Experiment 2: Eighty DOR patients were randomly divided into treatment and control groups (40 subjects each), then treated with ETG and placebo, respectively. granulosa cells were collected and subjected to quantitative polymerase chain reaction for analyzing the expression of specific miRNA found in experiment 1. We also compared fertilization rates, high-quality embryos, and clinical pregnancy rates between the 2 groups. Results: miRNA sequencing revealed differential expression of 81 miRNAs, of which 39 were downregulated, specially miR-214-3p and miR-193a-5p, whereas 42 were upregulated, specially let-7e-5p and miR-140-3p. In the second experiment, we found that miR-214-3p was significantly upregulated whereas let-7e-5p and miR-140-3p were significantly downregulated in the treatment group, relative to the control group (P < .05). Patients in the ETG treatment group exhibited a significantly higher fertilization rate than those in the control group (P < .05). Conclusion: ETG significantly increased fertilization rates in DOR patients with kidney deficiency syndrome and affected the expression of miR-214-3p, let-7e-5p, and miR-140-3p, the potential biomarkers.