Altered microRNA and gene expression in the follicular fluid of women with polycystic ovary syndrome

Abstract

Purpose To determine if microRNAs are differentially expressed in the follicular fluid of women with PCOS compared to fertile oocyte donors and identify associated altered gene expression. Methods Women undergoing IVF who met Rotterdam criteria for PCOS or who were fertile oocyte donors were recruited from a private IVF center. Individual follicle fluid was collected at the time of oocyte retrieval. MicroRNA analysis was performed using microarray and validated using real-time PCR on additional samples. Potential gene targets were identified and their expression analyzed by real time PCR. Results Microarray profiling of human follicular fluid revealed expression of 235 miRNAs, 29 were differentially expressed between the groups. Using PCR validation, 5 miRNAs (32, 34c, 135a, 18b, and 9) showed significantly increased expression in the PCOS group. Pathway analysis revealed genes involved in insulin regulation and inflammation. Three potential target genes were found to have significantly decreased expression in the PCOS group (interleukin 8, synaptogamin 1, and insulin receptor substrate 2).Conclusions MicroRNAs are differentially expressed in the follicular fluid of women with PCOS when compared to fertile oocyte donors. There is also altered expression of potential target genes associated with the PCOS phenotype.

Aberrant expression of long noncoding RNAs in cumulus cells isolated from PCOS patients

“…Noncoding RNAs are divided into short noncoding RNAs and long noncoding RNAs according to their length. Recent studies have revealed that microRNAs, the best-studied short noncoding RNAs, are differentially expressed in the follicular fluid of PCOS patients [17,18]. Moreover, an increasing body of evidence indicates that lncRNAs longer than 200 nucleotides play key roles in both normal development and diseases [15].…”

Epigenética del síndrome de ovario poliquístico

“…Sin embargo, un estudio posterior no observó este fenómeno, lo cual podría deberse a que los grupos estudiados pertenecían a diferentes etnias 41,42 . Éste último observó una expresión aumentada de 29 miRNA en mujeres con SOP, de estos, 5 miRNA (hsa-miR-9, 18b, 32, 34c y 135a) presentaron una sobreexpresión significativa en comparación a las controles.…”

“…Al mismo tiempo se observó una disminución en la expresión de tres genes: IRS2, SYT1 y IL8. Es probable que todos los miRNA diferencialmente expresados, posean un potencial inhibidor sobre estos genes, lo cual es relevante, ya que, estos genes están asociados al fenotipo SOP 42 .…”

In search of the transcriptional blueprints of a competent oocyte

“…Increasing evidences on the role of miRNAs during female reproduction point to an association between these molecules and several diseases, which generally affect oocyte developmental competence (Sirotkin et al, 2010;Roth et al, 2014) at least in humans. Although data in domestic animals are not available yet, it is of interest to consider this aspect as well, since it may have a wider impact than currently perceived.…”

“…They are found in the diverse compartments of ovarian follicles, including granulosa cells (Hatzirodos et al, 2014a), theca cells (Hatzidoros et al, 2014b), follicular fluid and oocytes (Bonnet et al, 2008). Studies demonstrated their role in follicle development of humans (Sirotkin et al, 2009;Sang et al, 2013;Roth et al, 2014), mice (Fiedler et al, 2008;Carletti et al, 2010), cattle (Tesfaye et al, 2009;Ma et al, 2011;Sohel et al, 2013), pigs (Lin et al, 2012;Donadeu and Schauer, 2013) and horses (Da Silveira et al, 2012). Data suggest that miRNAs may regulate cellular differentiation during follicular development and may contribute to the oocyte-somatic cells dialog during the acquisition of oocyte developmental competence.…”