Elevated circulating micro-ribonucleic acid (miRNA)-200b and miRNA-429 levels in anovulatory women.

OBJECTIVE

To study the role of micro-RNA (miRNA)-200b and miRNA-429 in human ovulation and to measure their expression levels in ovulatory and anovulatory patients.

DESIGN

Micro-RNA-200b and miRNA-429 expression analysis in human serum and granulosa cells at different phases of the ovulation cycle in normal cycling women and women undergoing assisted reproductive technology cycles.

SETTING

University-affiliated hospital and academic research laboratory.

PATIENT(S): Forty women (7 normally ovulating, 15 normally ovulating with pure male infertility factor, and 18 with polycystic ovary syndrome) were included in this study.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): The expression profile of circulating miRNAs and granulosa cells was assessed by means of real-time quantitative reverse transcription-polymerase chain reaction analysis.

RESULT(S): We identified miRNA-200b and miRNA-429 in the sera of all women tested. These miRNA expression levels were elevated during the early follicular phase of the cycle compared with serum levels during the early luteal phase. Anovulatory women, diagnosed with polycystic ovary syndrome, expressed significantly higher levels of miRNA-200b and miRNA-429 compared with spontaneously ovulating women. Ovulation induction with exogenous gonadotropins during an IVF cycle reduced these levels to the levels measured in normal ovulating women.

CONCLUSION(S): Our findings suggest an involvement of miRNA-200b and miRNA-429 in the pituitary regulation of human ovulation. Although it is unclear whether this altered miRNA expression profile is a cause or a result of anovulation, the levels of these molecules in the serum of anovulatory women may serve as serum biomarkers for the ovulation process.