title: DNA methylation and gene expression changes derived from assisted reproductive technologies can be decreased by reproductive fluids.
abstract: The number of children born since the origin of Assisted Reproductive Technologies (ART) exceeds 5 million. The majority seem healthy, but a higher frequency of defects has been reported among ART-conceived infants, suggesting an epigenetic cost. We report the first whole-genome DNA methylation datasets from single pig blastocysts showing differences between in vivo and in vitro produced embryos. Blastocysts were produced in vitro either without (C-IVF) or in the presence of natural reproductive fluids (Natur-IVF). Natur-IVF embryos were of higher quality than C-IVF in terms of cell number and hatching ability. RNA-Seq and DNA methylation analyses showed that Natur-IVF embryos have expression and methylation patterns closer to in vivo blastocysts. Genes involved in reprogramming, imprinting and development were affected by culture, with fewer aberrations in Natur-IVF embryos. Methylation analysis detected methylated changes in C-IVF, but not in Natur-IVF, at genes whose methylation could be critical, such as IGF2R and NNAT.
authors.affiliation: Physiology of Reproduction Group, Departamento de Fisiología, Facultad de Veterinaria, Universidad de Murcia-Campus Mare Nostrum, Murcia, Spain.|Instituto Murciano de Investigación Biosanitaria, Murcia, Spain.
authors.forename: Sebastian
authors.identifier: 0000-0003-4190-6258
authors.initials: S
authors.lastname: Canovas
authors.affiliation: Epigenetics Programme, The Babraham Institute, Cambridge, United Kingdom.
authors.forename: Elena
authors.initials: E
authors.lastname: Ivanova
authors.affiliation: Physiology of Reproduction Group, Departamento de Fisiología, Facultad de Veterinaria, Universidad de Murcia-Campus Mare Nostrum, Murcia, Spain.|Instituto Murciano de Investigación Biosanitaria, Murcia, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Romar
authors.affiliation: Physiology of Reproduction Group, Departamento de Fisiología, Facultad de Veterinaria, Universidad de Murcia-Campus Mare Nostrum, Murcia, Spain.|Instituto Murciano de Investigación Biosanitaria, Murcia, Spain.
authors.forename: Soledad
authors.initials: S
authors.lastname: García-Martínez
authors.affiliation: Physiology of Reproduction Group, Departamento de Fisiología, Facultad de Veterinaria, Universidad de Murcia-Campus Mare Nostrum, Murcia, Spain.|Instituto Murciano de Investigación Biosanitaria, Murcia, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Soriano-Úbeda
authors.affiliation: Physiology of Reproduction Group, Departamento de Fisiología, Facultad de Veterinaria, Universidad de Murcia-Campus Mare Nostrum, Murcia, Spain.|Instituto Murciano de Investigación Biosanitaria, Murcia, Spain.
authors.forename: Francisco A
authors.initials: FA
authors.lastname: García-Vázquez
authors.affiliation: Epigenetics Programme, The Babraham Institute, Cambridge, United Kingdom.|Bioinformatics Group, The Babraham Institute, Cambridge, United Kingdom.
authors.forename: Heba
authors.initials: H
authors.lastname: Saadeh
authors.affiliation: Bioinformatics Group, The Babraham Institute, Cambridge, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Andrews
authors.affiliation: Epigenetics Programme, The Babraham Institute, Cambridge, United Kingdom.|Centre for Trophoblast Research, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Gavin
authors.identifier: 0000-0002-9762-5634
authors.initials: G
authors.lastname: Kelsey
authors.affiliation: Physiology of Reproduction Group, Departamento de Fisiología, Facultad de Veterinaria, Universidad de Murcia-Campus Mare Nostrum, Murcia, Spain.|Instituto Murciano de Investigación Biosanitaria, Murcia, Spain.
authors.forename: Pilar
authors.identifier: 0000-0002-3943-1890
authors.initials: P
authors.lastname: Coy
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000502:physiology*; D000013:Congenital Abnormalities / Q000503:physiopathology*; D003470:Culture Media / Q000737:chemistry*; D004247:DNA / Q000737:chemistry; D019175:DNA Methylation; D004195:Disease Models, Animal; D015870:Gene Expression; D020869:Gene Expression Profiling; D027724:Reproductive Techniques, Assisted / Q000009:adverse effects*; D013552:Swine
chemical_list: D003470:Culture Media; D004247:DNA
keywords: In vitro fertilization; blastocyst; developmental biology; epigenetics; imprinting; pig; reproductive secretions; stem cells