title: Negative energy balance affects imprint stability in oocytes recovered from postpartum dairy cows.
abstract: Ovarian follicle development in post-partum, high-producing dairy cows, occurs in a compromised endogenous metabolic environment (referred to as negative energy balance, NEB). Key events that occur during oocyte/follicle growth, such as the vital process of genomic imprinting, may be detrimentally affected by this altered ovarian environment. Imprinting is crucial for placental function and regulation of fetal growth, therefore failure to establish and maintain imprints during oocyte growth may contribute to early embryonic loss. Using ovum pick-up (OPU), oocytes and follicular fluid samples were recovered from cows between days 20 and 115 post-calving, encompassing the NEB period. In a complimentary study, cumulus oocyte complexes were in vitro matured under high non-esterified fatty acid (NEFA) concentrations and in the presence of the methyl-donor S-adenosylmethionine (SAM). Pyrosequencing revealed the loss of methylation at several imprinted loci in the OPU derived oocytes. The loss of DNA methylation was observed at the PLAGL1 locus in oocytes, following in vitro maturation (IVM) in the presence of elevated NEFAs and SAM. Finally, metabolomic analysis of postpartum follicular fluid samples revealed significant differences in several branched chain amino acids, with fatty acid profiles bearing similarities to those characteristic of lactating dairy cows. These results provide the first evidence that (1) the postpartum ovarian environment may affect maternal imprint acquisition and (2) elevated NEFAs during IVM can lead to the loss of imprinted gene methylation in bovine oocytes.
authors.affiliation: School of Agriculture & Food Science, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Alan M
authors.initials: AM
authors.lastname: O'Doherty
authors.affiliation: School of Agriculture & Food Science, University College Dublin, Belfield, Dublin 4, Ireland; Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Aoife
authors.initials: A
authors.lastname: O'Gorman
authors.affiliation: Lyons Research Farm, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Abdullah
authors.initials: A
authors.lastname: al Naib
authors.affiliation: School of Agriculture & Food Science, University College Dublin, Belfield, Dublin 4, Ireland; Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Brennan
authors.affiliation: Lyons Research Farm, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Edward
authors.initials: E
authors.lastname: Daly
authors.affiliation: Lyons Research Farm, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Pat
authors.initials: P
authors.lastname: Duffy
authors.affiliation: School of Agriculture & Food Science, University College Dublin, Belfield, Dublin 4, Ireland. Electronic address: trudee.fair@ucd.ie.
authors.forename: Trudee
authors.initials: T
authors.lastname: Fair
mesh_terms: D000818:Animals; D002417:Cattle / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D019175:DNA Methylation; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D015571:Follicular Fluid / Q000378:metabolism; D018392:Genomic Imprinting; D055442:Metabolome; D009865:Oocytes / Q000378:metabolism*; D049590:Postpartum Period / Q000235:genetics* / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics
chemical_list: D005230:Fatty Acids, Nonesterified; D014157:Transcription Factors; D012436:S-Adenosylmethionine
keywords: DNA methylation; Environment; Epigenetics; Imprinting; Negative energy balance; Oocyte