{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:42:45Z","timestamp":1791895365487,"version":"4.3.4"},"reference-count":78,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T00:00:00Z","timestamp":1631059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017642","name":"Spanish National Plan for Scientific and Technical Research and Innovation","doi-asserted-by":"publisher","award":["AGL2014-53405-C2-1-P"],"award-info":[{"award-number":["AGL2014-53405-C2-1-P"]}],"id":[{"id":"10.13039\/501100017642","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011596","name":"Conselleria d'Educaci\u00f3, Investigaci\u00f3, Cultura i Esport","doi-asserted-by":"publisher","award":["Prometeo II 2014\/036"],"award-info":[{"award-number":["Prometeo II 2014\/036"]}],"id":[{"id":"10.13039\/501100011596","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms22189716","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T10:12:03Z","timestamp":1631095923000},"page":"9716","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Early Embryo Exposure to Assisted Reproductive Manipulation Induced Subtle Changes in Liver Epigenetics with No Apparent Negative Health Consequences in Rabbit"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3022-8092","authenticated-orcid":false,"given":"Ximo","family":"Garc\u00eda-Dom\u00ednguez","sequence":"first","affiliation":[{"name":"Laboratory of Biotechnology of Reproduction, Institute for Animal Science and Technology (ICTA), Universitat Polit\u00e8cnica de Valencia, 46022 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1441-0233","authenticated-orcid":false,"given":"Gianfranco","family":"Diretto","sequence":"additional","affiliation":[{"name":"Casaccia Research Centre, Italian National Agency for New Technologies, Energy and Sustainable Development (ENEA), 00123 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0861-976X","authenticated-orcid":false,"given":"David S.","family":"Pe\u00f1aranda","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology of Reproduction, Institute for Animal Science and Technology (ICTA), Universitat Polit\u00e8cnica de Valencia, 46022 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8161-3797","authenticated-orcid":false,"given":"Sarah","family":"Frusciante","sequence":"additional","affiliation":[{"name":"Casaccia Research Centre, Italian National Agency for New Technologies, Energy and Sustainable Development (ENEA), 00123 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Garc\u00eda-Carpintero","sequence":"additional","affiliation":[{"name":"Institute for the Conservation and Breeding of Agricultural Biodiversity (COMAV-UPV), Universitat Polit\u00e8cnica de Valencia, 46022 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"Ca\u00f1izares","sequence":"additional","affiliation":[{"name":"Institute for the Conservation and Breeding of Agricultural Biodiversity (COMAV-UPV), Universitat Polit\u00e8cnica de Valencia, 46022 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0481-3802","authenticated-orcid":false,"given":"Jos\u00e9 S.","family":"Vicente","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology of Reproduction, Institute for Animal Science and Technology (ICTA), Universitat Polit\u00e8cnica de Valencia, 46022 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5226-4118","authenticated-orcid":false,"given":"Francisco","family":"Marco-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Laboratory of Biotechnology of Reproduction, Institute for Animal Science and Technology (ICTA), Universitat Polit\u00e8cnica de Valencia, 46022 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.biocel.2015.04.014","article-title":"Germline-derived DNA methylation and early embryo epigenetic reprogramming: The selected survival of imprints","volume":"67","author":"Monk","year":"2015","journal-title":"Int. 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