Abstract
Embryo manipulation is a requisite step in assisted reproductive technology (ART). Therefore, it is of great necessity to appraise the safety of ART and investigate the long-term effect, including lipid metabolism, on ART-conceived offspring. Augmenting our ART rabbit model to investigate lipid metabolic outcomes in offspring longitudinally, we detected variations in hepatic DNA methylation ART offspring in the F3 generation for embryonic exposure (multiple ovulation, vitrification and embryo transfer). Through adult liver metabolomics and proteomics, we identified changes mainly related to lipid metabolism (e.g., polyunsaturated fatty acids, steroids, steroid hormone). We also found that DNA methylation analysis was linked to changes in lipid metabolism and apoptosis genes. Nevertheless, these differences did not apparently alter the general health status. Thus, our findings suggest that ART is likely to be a player in embryo epigenetic events related to hepatic homeostasis alteration in adulthood.
Highlights
During the preimplantation period, major epigenetic reprogramming occurs to provide the developing embryo with an epigenetic profile coherent with pluripotency, from which differentiated cells acquire lineage-specific transcriptional profile [1]
A specific circumstance is that assisted reproductive technology (ART) handling occurs during preimplantation development, coinciding with global reprogramming of the epigenome and the establishment of epigenetic changes that persist into adulthood [2,5,6,7]
We performed an analysis of DNA methylation profile in liver tissue in a cohort of F3 generation animals conceived by MOVET and compared findings with counterpart naturally conceived animals
Summary
Major epigenetic reprogramming occurs to provide the developing embryo with an epigenetic profile coherent with pluripotency, from which differentiated cells acquire lineage-specific transcriptional profile [1]. Stressful exposures outside their natural range in mammalian embryos that have not evolved appropriate mechanisms may result in non-adaptive responses [4]. This theory, called developmental origins of health and disease (DOHaD), postulates that a suboptimal environment during embryo or fetal development may lead to adjustments in the anatomy, physiology and metabolism of various organ systems and thereby influence disease susceptibility [3,4]. A specific circumstance is that assisted reproductive technology (ART) handling occurs during preimplantation development, coinciding with global reprogramming of the epigenome and the establishment of epigenetic changes that persist into adulthood [2,5,6,7]
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