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Inheritance of acquired epigenetic modifications by the next generation occurs through the germline, although the precise mechanisms remain to be elucidated. Here, we used a sheep model to evaluate if modification of the maternal diet (CTR; control, UND: undernutrition; FA: undernutrition and folic acid supplementation) during the peri-conceptional period affects the genome-wide methylation status of the gametes of male offspring. Sperm DNA methylation, measured by Reduced Representation Bisulfite Sequencing (RRBS), identified Differentially Methylated Regions (DMR) in offspring that experienced in utero undernutrition, both in UND (244) and FA (240), compared with CTR. Gene ontology (GO) analysis identified DMRs in categories related to sperm function, therefore we investigated whether the fertilizing capacity of the semen from the three groups differed in an in vitro fertilization assay. Spermatozoa from the undernourished groups showed lower motility and sperm chromatin structure abnormalities, represented by a higher percentage of DNA fragmentation and an increased number of immature cells, compared with CTR. While good quality blastocysts were obtained from all three groups, the proportion of embryos reaching the blastocyst stage was reduced in the UND vs CTR, an effect partially rescued by the FA treatment. The data reported here show that nutritional stress during early pregnancy leads to epigenetic modifications in the semen of the resulting offspring, the effects of which in next generation remain to be elucidated.<\/jats:p>","DOI":"10.1530\/rep-19-0549","type":"journal-article","created":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T06:30:36Z","timestamp":1582785036000},"page":"513-523","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-11","source":"Crossref","is-referenced-by-count":26,"title":["Maternal peri-conceptional undernourishment perturbs offspring sperm methylome"],"prefix":"10.1093","volume":"159","author":[{"given":"Paola","family":"Toschi","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Embryology , Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Capra","sequence":"additional","affiliation":[{"name":"Department of Animal Science , Food and Technology \u2013 DIANA, and Nutrigenomics and Proteomics Research Center \u2013 PRONUTRIGEN, Universit\u00e0 Cattolica del Sacro Cuore, Piacenza, Italy"},{"name":"Institute of Agricultural Biology and Biotechnology (IBBA) , National Research Council (CNR), Lodi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora A","family":"Anzalone","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Embryology , Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Lazzari","sequence":"additional","affiliation":[{"name":"Department of Animal Science , Food and Technology \u2013 DIANA, and Nutrigenomics and Proteomics Research Center \u2013 PRONUTRIGEN, Universit\u00e0 Cattolica del Sacro Cuore, Piacenza, Italy"},{"name":"Institute of Agricultural Biology and Biotechnology (IBBA) , National Research Council (CNR), Lodi, 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