Abnormal PIWI-interacting RNA profile and its association with the deformed extracellular matrix of oocytes from recurrent oocyte maturation arrest patients

Objective To depict the PIWI-interacting RNA (piRNA) profile in oocytes from patients with recurrent oocyte maturation arrest (ROMA) and explore the piRNA candidates associated with the disease. Design An observational study. Setting Academic research unit. Patient(s) Sixteen ROMA patients who provided 140 immature oocytes that arrested at metaphase I, and 146 control patients who provided 420 oocytes for in vitro culture that were collected at the stages of germinal vesicle (GV), metaphase I (MI), and MII. Intervention(s) None. Main Outcome Measure(s) Expression profiles of piRNA and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) validating data of piR-hsa-17139 and its target genes. Result(s) After the piRNA profile was established using piRNA sequencing and hierarchical clustering, the target genes of the piRNA were predicted by bioinformatics databases and matched with mRNA sequencing data. The piRNA expression profiles showed a greater quantity of differentially expressed piRNAs in the older-stage oocytes compared with the early-stage oocytes. The piRNA and mRNA sequencing data indicated that the most affected genes were mainly concentrated in the extracellular matrix (ECM) pathway. Based on the comparison of the piRNA and mRNA sequencing data, four differentially expressed piRNAs were associated with modulation of those ECM pathway genes. The qRT-PCR validation confirmed that piR-hsa-17139 was the only up-regulated piRNA, and its target ECM genes were suppressed in ROMA oocytes. The expression level of piR-hsa-17139 declined slightly while the expression of its target ECM genes plunged dramatically during the development of normal oocytes. Conclusion(s): As the important genome monitors in gametogenesis, abnormally expressed piRNAs may affect the expression of ECM modulating genes, which subsequently contributes to ROMA.