RUNX2, GPX3 and PTX3 gene expression profiling in cumulus cells are reflective oocyte/embryo competence and potentially reliable predictors of embryo developmental competence in PCOS patients

Abstract

BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women. The developmental competence of oocytes and embryos in PCOS patients is reduced to a certain extent (comparing to non-PCOS patients, the high quality embryo rate was decreased by 16% from the data of our centre) during the in vitro fertilization (IVF) process. Cross-talk between the oocyte and cumulus cells is critical for oocyte maturation and embryo competence. In this study, we have evaluated the transcription of specific genes in cumulus cells harvested from pre-ovulatory follicles of PCOS patients before IVF, according to individual oocyte nuclear maturity and developmental competence. Seven genes (RUNX2, PSAT1, ADAMTS9, CXCL1, CXCL2, CXCL3, and ITGB5) were targeted from our previous cDNA microarray data which isolated genes related to oocyte nuclear maturation in PCOS patients. Two additional genes which had been found to be associated with oocyte maturation or embryo quality in non-PCOS patients (GPX3 and PTX3) were also studied.MethodsThe mRNA expression levels of cumulus cells were detected by qRT- PCR.ResultsConsistent with our previous cDNA microarray data, with the exception of GPX3 and PTX3, the selected 7 genes were related to oocyte nuclear maturation in PCOS patients. Noticeably, the expression level of RUNX2 was lower in cumulus cells derived from oocytes that could develop into blastocysts than the level of expression from oocytes that could not. The PTX3 expression level was significantly lower in cumulus cells from oocytes with two normal pronuclei than that from oocytes that formed >2 pronuclei (MPN) after fertilization. GPX3 mRNA levels were decreased in cumulus cells isolated from oocytes that developed into blastocysts with high potential development competence.ConclusionsSeveral cumulus cell genes were associated with oocyte maturation, fertilization and embryo quality in PCOS patients. RUNX2 and GPX3 are candidate genetic markers in the monitoring of embryo quality for PCOS patients, whereas PTX3 mainly played a role in fertilization process. Together with morphological evaluation, cumulus cells genes may serve as biomarkers of oocyte and embryo selection during the IVF process for PCOS patients and may advance our understanding of PCOS.

Embryo splitting affects the transcriptome during elongation stage of in vitro–produced bovine blastocysts

“…ADAM metallopeptidase is a member of the protein family disintegrin and metalloproteinases with thrombospondin motif. Members of this family are associated with various inflammatory processes as well as with inhibition of angiogenesis, normal growth, fertility, organ morphology and function [58] and embryo survival after Day 12 in Adamts9 null mice [59,60].…”

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

“…The cumulus cells were retrieved, and the oocytes were cultured and inseminated as described previously [29]. In brief, after COC retrieval, a proportion of the CCs surrounding a single oocyte was removed using a sharp needle, lysed in 80 μl of RLT buffer (RNeasy Mini Kit, Qiagen) supplemented with 1 % (v/v) 2-β-mercaptoethanol (M-3148; Sigma, Lyon, France), and stored at −80°C until RNA extraction.…”

Growth differentiation factor 8 down-regulates pentraxin 3 in human granulosa cells

“…Aside from ovulatory dysfunction, PCOS patients often encounter poor fertilization rates of retrieved oocytes during in vitro fertilization treatment (Jabara and Coutifaris, 2003). Indeed, the expression levels of PTX3 in cumulus cells have been shown to positively correlate with the quality and fertilization rates of the corresponding oocytes (Huang et al, 2013;Zhang et al, 2005). Interestingly, serum GDF8 concentrations were shown to be higher in women with PCOS than those without PCOS (Chen et al, 2012).…”