Diterpenoid fingerprints in pine foliage across an environmental and chemotypic matrix: Isoabienol content is a key trait differentiating chemotypes.

Diterpenoids constitute an important part of oleoresin in conifer needles, but the environmental and genetic controls on diterpenoid composition are poorly known. We studied the presence of diterpenoids in four pine populations spanning an extensive range of nitrogen (N) availability. In most samples, isoabienol was the main diterpenoid. Additionally, low contents of (Z)-biformene, abietadiene isomers, manoyl oxide isomers, labda-7,13,14-triene and labda-7,14-dien-13-ol were quantified in pine needles. According to the occurrence and content of diterpenoids it was possible to distinguish 'non diterpenoid pines', 'high isoabienol pines', 'manoyl oxide - isoabienol pines' and 'other diterpenoid pines'. 'Non diterpenoid pines', 'high isoabienol pines' and 'other diterpenoid pines' were characteristic to the dry forest, yet the majority of pines (>80%) of the bog Laeva represented 'high isoabienol pines'. 'Manoyl oxide - isoabienol pines' were present only in the wet sites. Additionally, orthogonal partial least-squares analysis showed, that in the bogs foliar nitrogen content per dry mass (NM) correlated to diterpenoids. Significant correlations existed between abietadienes, isoabienol and foliar NM in 'manoyl oxide - isoabienol pines', and chemotypic variation was also associated by population genetic distance estimated by nuclear microsatellite markers. Previously, the presence of low and high Δ-3-carene pines has been demonstrated, but the results of the current study indicate that also diterpenoids form an independent axis of chemotypic differentiation. Further studies are needed to understand whether the enhanced abundance of diterpenoids in wetter sites reflects a phenotypic or genotypic response.

Meta-signature of human endometrial receptivity: a meta-analysis and validation study of transcriptomic biomarkers.

Previous transcriptome studies of the human endometrium have revealed hundreds of simultaneously up- and down-regulated genes that are involved in endometrial receptivity. However, the overlap between the studies is relatively small, and we are still searching for potential diagnostic biomarkers. Here we perform a meta-analysis of endometrial-receptivity associated genes on 164 endometrial samples (76 from 'pre-receptive' and 88 from mid-secretory, 'receptive' phase endometria) using a robust rank aggregation (RRA) method, followed by enrichment analysis, and regulatory microRNA prediction. We identify a meta-signature of endometrial receptivity involving 57 mRNA genes as putative receptivity markers, where 39 of these we confirm experimentally using RNA-sequencing method in two separate datasets. The meta-signature genes highlight the importance of immune responses, the complement cascade pathway and the involvement of exosomes in mid-secretory endometrial functions. Bioinformatic prediction identifies 348 microRNAs that could regulate 30 endometrial-receptivity associated genes, and we confirm experimentally the decreased expression of 19 microRNAs with 11 corresponding up-regulated meta-signature genes in our validation experiments. The 57 identified meta-signature genes and involved pathways, together with their regulatory microRNAs could serve as promising and sought-after biomarkers of endometrial receptivity, fertility and infertility.

DNA methylation changes in endometrium and correlation with gene expression during the transition from pre-receptive to receptive phase.

The inner uterine lining (endometrium) is a unique tissue going through remarkable changes each menstrual cycle. Endometrium has its characteristic DNA methylation profile, although not much is known about the endometrial methylome changes throughout the menstrual cycle. The impact of methylome changes on gene expression and thereby on the function of the tissue, including establishing receptivity to implanting embryo, is also unclear. Therefore, this study used genome-wide technologies to characterize the methylome and the correlation between DNA methylation and gene expression in endometrial biopsies collected from 17 healthy fertile-aged women from pre-receptive and receptive phase within one menstrual cycle. Our study showed that the overall methylome remains relatively stable during this stage of the menstrual cycle, with small-scale changes affecting 5% of the studied CpG sites (22,272 out of studied 437,022 CpGs, FDR < 0.05). Of differentially methylated CpG sites with the largest absolute changes in methylation level, approximately 30% correlated with gene expression measured by RNA sequencing, with negative correlations being more common in 5' UTR and positive correlations in the gene 'Body' region. According to our results, extracellular matrix organization and immune response are the pathways most affected by methylation changes during the transition from pre-receptive to receptive phase.