Expression of microRNAs and isomiRs in the porcine endometrium: implications for gene regulation at the maternal-conceptus interface

Abstract

BackgroundEmbryo implantation is a complex, synchronized process that requires establishment of a reciprocal dialogue between a receptive endometrium and developing blastocysts. Recently, microRNAs (miRNAs), known to modulate gene expression through post-transcriptional mechanisms, were implicated in regulation of early pregnancy events including maternal recognition of pregnancy and implantation. To characterize complex transcriptomic changes, expression of miRNAs in pregnant and cyclic endometria collected on days 12, 16 and 20 was analyzed using Illumina deep sequencing and analyzed with bioinformatic pipeline. Moreover, expression profiles of ten genes related to miRNA synthesis and transport such as DROSHA, DGCR8, XPO5, DICER, TARBP2, TNRC6A, and AGO1-4 were determined.ResultsAmong genes involved in miRNA transport and synthesis DROSHA, XPO5, DICER1, TARBP, and AGO1 expression was affected by the reproductive status. Moreover, DICER1 and AGO2 proteins were localized in luminal and glandular epithelium with immunofluorescence staining. Several hundred mature, canonical and non-canonical miRNAs were found to be expressed in the endometrial samples. Detailed analysis revealed that miRNA length variants, isomiRs, accounted for the vast majority of defined sequences. Both miRNA and isomiR of miR-140-3p were shown to affect expression of putative targets in endometrial stromal cells in vitro. Computational analysis of putative target genes for miRNAs differentially expressed (DE) between pregnant and cyclic animals resulted in lists of biological processes and regulatory pathways indicating their role in cellular development, cell cycle, immunological response and organismal development. Among predicted target genes for DE miRNAs, vascular endothelial growth factor (VEGF), progesterone and estradiol receptors (PGR, ESR1) and leukemia inhibitory factor (LIF) were found.ConclusionsThis research revealed a repertoire of pregnancy-related miRNAs in porcine endometrium during initial stages of conceptus implantation and during the estrous cycle, and sheds light on mechanisms regulating miRNA-mediated gene expression at the maternal-conceptus interface.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2172-2) contains supplementary material, which is available to authorized users.

Peri‐conceptional under‐nutrition alters transcriptomic profile in the endometrium during the peri‐implantation period—The study in domestic pigs

“…We found that restricted diet may decrease the expression of genes encoded proteins which are involved in the formation of exosome vesicles in the endometrium (Tannetta, Dragovic, Alyahyaei, & Southcombe, ). It was found that exosomes may contain miRNA that contributes to proper development of endometrial‐embryo cross‐talk (Krawczynski, Bauersachs, Reliszko, Graf, & Kaczmarek, ). Observed in our study decreased expression of genes involved in the formation of exosome vesicles may indicate that restricted diet during peri‐conceptional period affects the mechanisms of endometrial‐embryo cross‐talk mediated via components of exosome vesicles.…”

MiRNAs in the Peri-Implantation Period: Contribution to Embryo–Maternal Communication in Pigs

“…Recently, pregnancy stage-dependent expression profiles of genes involved in miRNA synthesis and transport were demonstrated in porcine conceptuses, trophoblasts, and endometria [22,23]. Uterine glands and luminal epithelia were the only sites of DICER1 and AGO2 immunoreactivity, where miRNA biogenesis seems likely to occur during early pregnancy in pigs.…”

Impact of preimplantational oral low‐dose estradiol‐17β exposure on the endometrium: The role of miRNA

“…Expression profiling has identified a large number of miRNAs in reproductive tissues, including the ovary and the endometrium (Chegini, 2010;Su et al, 2014). Endometrial miRNAs have been associated with the regulation of genes that are important for differentiation, proliferations, receptivity, extracellular matrix factors, angiogenesis, and immunological response processes, which are crucial in preparation of the endometrium for implantation (Bidarimath et al, 2014;Krawczynski, Bauersachs, Reliszko, Graf, & Kaczmarek, 2015;Wessels et al, 2013). Steroid hormones and their respective receptors such as estrogen receptors (ER) α and β largely control these processes (Chegini, 2010).…”