{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:47:56Z","timestamp":1790876876463,"version":"4.1.0"},"reference-count":86,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,2,1]],"date-time":"2020-02-01T00:00:00Z","timestamp":1580515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Flemish Research Fund","award":["11L8716N"],"award-info":[{"award-number":["11L8716N"]}]},{"name":"Flemish Research Fund","award":["42\/FAO10300\/6541"],"award-info":[{"award-number":["42\/FAO10300\/6541"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>STUDY QUESTION<\/jats:title>\n                  <jats:p>Does oocyte maturation under lipolytic conditions have detrimental carry-over effects on post-hatching embryo development of good-quality blastocysts after transfer?<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>SUMMARY ANSWER<\/jats:title>\n                  <jats:p>Surviving, morphologically normal blastocysts derived from bovine oocytes that matured under lipotoxic conditions exhibit long-lasting cellular dysfunction at the transcriptomic and metabolic levels, which coincides with retarded post-hatching embryo development.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                  <jats:p>There is increasing evidence showing that following maturation in pathophysiologically relevant lipotoxic conditions (as in obesity or metabolic syndrome), surviving blastocysts of good (transferable) morphological quality have persistent transcriptomic and epigenetic alteration even when in vitro embryo culture takes place under standard conditions. However, very little is known about subsequent development in the uterus after transfer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                  <jats:p>Bovine oocytes were matured in vitro in the presence of pathophysiologically relevant, high non-esterified fatty acid (NEFA) concentrations (HIGH PA), or in basal NEFA concentrations (BASAL) as a physiological control. Eight healthy multiparous non-lactating Holstein cows were used for embryo transfers. Good-quality blastocysts (pools of eight) were transferred per cow, and cows were crossed over for treatments in the next replicate. Embryos were recovered 7\u00a0days later and assessed for post-hatching development, phenotypic features and gene expression profile. Blastocysts from solvent-free and NEFA-free maturation (CONTROL) were also tested for comparison.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                  <jats:p>Recovered Day 14 embryos were morphologically assessed and dissected into embryonic disk (ED) and extraembryonic tissue (EXT). Samples of EXT were cultured for 24\u00a0h to assess cellular metabolic activity (glucose and pyruvate consumption and lactate production) and embryos\u2019 ability to signal for maternal recognition of pregnancy (interferon-\u03c4 secretion; IFN-\u03c4). ED and EXT samples were subjected to RNA sequencing to evaluate the genome-wide transcriptome patterns.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                  <jats:p>The embryo recovery rate at Day 14 p.i. was not significantly different among treatment groups (P\u00a0&amp;gt;\u20090.1). However, higher proportions of HIGH PA embryos were retarded in growth (in spherical stage) compared to the more elongated tubular stage embryos in the BASAL group (P\u00a0&amp;lt;\u20090.05). Focusing on the normally developed tubular embryos in both groups, HIGH PA exposure resulted in altered cellular metabolism and altered transcriptome profile particularly in pathways related to redox-regulating mechanisms, apoptosis, cellular growth, interaction and differentiation, energy metabolism and epigenetic mechanisms, compared to BASAL embryos. Maturation under BASAL conditions did not have any significant effects on post-hatching development and cellular functions compared to CONTROL.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>LARGE-SCALE DATA<\/jats:title>\n                  <jats:p>The datasets of RNA sequencing analysis are available in the NCBI\u2019s Gene Expression Omnibus (GEO) repository, series accession number GSE127889 (https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE127889). Datasets of differentially expressed genes and their gene ontology functions are available in the Mendeley datasets at http:\/\/dx.doi.org\/10.17632\/my2z7dvk9j.2.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                  <jats:p>The bovine model was used here to allow non-invasive embryo transfer and post-hatching recovery on Day 14. There are physiological differences in some characteristics of post-hatching embryo development between human and cows, such as embryo elongation and trophoblastic invasion. However, the main carry-over effects of oocyte maturation under lipolytic conditions described here are evident at the cellular level and therefore may also occur during post-hatching development in other species including humans. In addition, post-hatching development was studied here under a healthy uterine environment to focus on carry-over effects originating from the oocyte, whereas additional detrimental effects may be induced by maternal metabolic disorders due to adverse changes in the uterine microenvironment. RNA sequencing results were not verified by qPCR, and no solvent control was included.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                  <jats:p>Our observations may increase the awareness of the importance of maternal metabolic stress at the level of the preovulatory oocyte in relation to carry-over effects that may persist in the transferrable embryos. It should further stimulate new research about preventive and protective strategies to optimize maternal metabolic health around conception to maximize embryo viability and thus fertility outcome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                  <jats:p>This study was supported by the Flemish Research Fund (FWO grant 11L8716N and FWO project 42\/FAO10300\/6541). The authors declare there are no conflicts of interest.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/humrep\/dez248","type":"journal-article","created":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T14:38:49Z","timestamp":1571927929000},"page":"293-307","source":"Crossref","is-referenced-by-count":28,"title":["Oocyte maturation under lipotoxic conditions induces carryover transcriptomic and functional alterations during post-hatching development of good-quality blastocysts: novel insights from a bovine embryo-transfer model"],"prefix":"10.1093","volume":"35","author":[{"given":"Karolien L J","family":"Desmet","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waleed F A","family":"Marei","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, 2610 Wilrijk, Belgium"},{"name":"Department of Theriogenology, Faculty of Veterinary Medicine, Cairo University, 12211 Giza, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Richard","sequence":"first","affiliation":[{"name":"UMR Biologie du D\u00e9veloppement et Reproduction, Institut National de la Recherche Agronomique (INRA), \u00c9cole Nationale V\u00e9t\u00e9rinaire d'Alford, Universit\u00e9 Paris-Saclay, 78352 Jouy-en-Josas, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrien","family":"Sprangers","sequence":"first","affiliation":[{"name":"Integrated Molecular Plant Physiology Research Group (IMPRES), Department of Biology, University of Antwerp, 2020 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerrit T S","family":"Beemster","sequence":"first","affiliation":[{"name":"Integrated Molecular Plant Physiology Research Group (IMPRES), Department of Biology, University of Antwerp, 2020 Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Meysman","sequence":"first","affiliation":[{"name":"Biomedical Informatics Research Center Antwerp, Department of Mathematics and Computer Science, University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kris","family":"Laukens","sequence":"first","affiliation":[{"name":"Biomedical Informatics Research Center Antwerp, Department of Mathematics and Computer Science, University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Declerck","sequence":"first","affiliation":[{"name":"Laboratory of Protein Science, Proteomics and Epigenetic Signaling, Department of Biomedical Sciences, University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim","family":"Vanden Berghe","sequence":"first","affiliation":[{"name":"Laboratory of Protein Science, Proteomics and Epigenetic Signaling, Department of Biomedical Sciences, University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter E J","family":"Bols","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, 2610 Wilrijk, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Hue","sequence":"first","affiliation":[{"name":"UMR Biologie du D\u00e9veloppement et Reproduction, Institut National de la Recherche Agronomique (INRA), \u00c9cole Nationale V\u00e9t\u00e9rinaire d'Alford, Universit\u00e9 Paris-Saclay, 78352 Jouy-en-Josas, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo L M 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