Identification of sex-dependent epigenetic signatures of the bovine conceptus associated with its developmental potential and its response to different maternal microenvironment during early elongation stage
Final Report Abstract
The aim of this study was to investigate the sex-specific transcriptome and DNA methylome signatures induced in the male or female bovine early elongation-stage conceptus by the physiological status of the mothers and to investigate transcriptome and epigenome markers of early elongation-stage conceptus in relation to its developmental potential. Therefore, we investigated the influences of the maternal environment on the transcriptome and epigenome signatures of male and female early elongation-stage embryos by transferring male and female early cleavage-stage embryos into the oviduct of Holstein Friesian cows and heifers and recollected these at day 13 of conception. The transcriptome profile indicated sexual dimorphic gene expression patterns in early elongation-stage embryos. More detailed, male and female early elongation-stage embryos which developed in cows showed differential expression of genes associated with lipid metabolism, homeostasis and steroid biosynthesis whereas male and female embryos which developed in heifers showed differential expression of genes involved in tissue development, female sex differentiation and placental development. Similarly, our study confirmed sexual dimorphic miRNA expression in early elongation-stage embryos. While male and female embryos developed in cows showed differential expression of miRNAs associated with the immune system, mTOR signalling, cell-to-cell communication and cell proliferation, male and female embryos developed in heifers showed differential expression of only four miRNAs, suggesting that the maternal environment of the cow could induce differences in miRNA expression between male and female embryos. These findings were in line with the sexual dimorphic DNA methylome signatures in which 172741 and 127905 CpG sites found to be differentially methylated between male and female early elongation-stage embryos which developed in cows and heifers, respectively. On the other hand, our study clearly uncovered a marked effect of the maternal environment on the epigenome of the early elongation-stage embryo with male embryos being more sensitive. Moreover, early elongation stage embryos that resulted in pregnancy until Day 50 of the gestation period showed a differential expression of 75 genes that could be involved in regulation of metabolic processes, system development and vascular development, compared to those ending up in no pregnancy. In line with these results, the DNA methylation analysis identified 60893 and 120585 CpG sites as well as 13792 and 48653 CpG sites overlapping with genes in elongated male and female embryos, respectively whose methylation patterns were significantly different between those resulting in pregnancy and no pregnancy. Interestingly, we also uncovered sexual dimorphic methylome signatures in early elongation-stage embryos ending up in conception. Thus, sexual dimorphic transcriptome and DNA methylome profiles in early elongation stage embryos reflecting the physiological status of the mother as well as being predictive for developmental capacity may indicate sex-specific molecular responses which may also contribute to skewed sex ratios at birth in cattle.
Publications
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63 Maternal microenvironment-induced, sex-specific microRNA expression patterns during the early elongation stage of bovine embryo development. Reproduction, Fertility and Development, 35(2), 158-158.
Salilew-Wondim, D.; Blaschka, C.; Tholen, E.; Tesfaye, D.; Besenfelder, U.; Havlicek, V. & Hoelker, M.
