Functional signaling and gene regulatory networks between the oocyte and the surrounding cumulus cells

Abstract

BackgroundThe maturation and successful acquisition of developmental competence by an oocyte, the female gamete, during folliculogenesis is highly dependent on molecular interactions with somatic cells. Most of the cellular interactions identified, thus far, are modulated by growth factors, ions or metabolites. We hypothesized that this interaction is also modulated at the transcriptional level, which leads to the formation of gene regulatory networks between the oocyte and cumulus cells. We tested this hypothesis by analyzing transcriptome data from single oocytes and the surrounding cumulus cells collected from antral follicles employing an analytical framework to determine interdependencies at the transcript level.ResultsWe overlapped our transcriptome data with putative protein-protein interactions and identified hundreds of ligand-receptor pairs that can transduce paracrine signaling between an oocyte and cumulus cells. We determined that 499 ligand-encoding genes expressed in oocytes and cumulus cells are functionally associated with transcription regulation (FDR < 0.05). Ligand-encoding genes with specific expression in oocytes or cumulus cells were enriched for biological functions that are likely associated with the coordinated formation of transzonal projections from cumulus cells that reach the oocyte’s membrane. Thousands of gene pairs exhibit significant linear co-expression (absolute correlation > 0.85, FDR < 1.8 × 10− 5) patterns between oocytes and cumulus cells. Hundreds of co-expressing genes showed clustering patterns associated with biological functions (FDR < 0.5) necessary for a coordinated function between the oocyte and cumulus cells during folliculogenesis (i.e. regulation of transcription, translation, apoptosis, cell differentiation and transport).ConclusionOur analyses revealed a complex and functional gene regulatory circuit between the oocyte and surrounding cumulus cells. The regulatory profile of each cumulus-oocyte complex is likely associated with the oocytes’ developmental potential to derive an embryo.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4738-2) contains supplementary material, which is available to authorized users.

Rewiring of gene expression in circulating white blood cells is associated with pregnancy outcome in heifers (Bos taurus)

“…Sequences were submitted to a custom build bioinformatics pipeline 74,75,76 . Reads were aligned to the bovine genome (ARS-UCD1.2 obtained from Ensembl 77 ) using HISAT2 78 .…”

“…Significance was estimated by the eFDR approach 75,89,90 . We resampled (5000 randomizations) the labels of pregnancy outcome and calculated r for each pair of genes in the scrambled data set ( r scramble ).…”

“…: for r=0.99, eFDR<0.002, Supplementary Fig. 1), relative to the total number of correlations calculated using the formulas described elsewhere 75,89,90 .…”

“…We calculated Pearson’s correlation ( r ) 86,87 values between miRNA and mRNA genes for all 17 samples. Significance was estimated by the eFDR approach 75,89,90 by shuffling (5000 randomizations) the animal identification on mRNA dataset, thus breaking the common source of both RNA types (Supplementary Fig. 2).…”

“…This nominal P value corresponded to eFDR≤0.05 (Supplementary Fig. 4), as calculated according to the procedure and formulas outlined elsewhere 75,89,90 using 10000 randomizations of sample reshuffling. Genes inferred as differentially expressed based on P values were further selected through “leave-one-out” cross validation 94,95 .…”