title: Insulin exposure during in vitro bovine oocyte maturation changes blastocyst gene expression and developmental potential.
abstract: Metabolic imbalance impairs fertility, because changes in concentrations of metabolites and hormones in the blood and follicular fluid create an unfavourable environment for early embryonic development. Insulin is a key metabolic hormone known for its effects on fertility: insulin concentrations are increased during energy balance disturbances in diabetes or metabolic syndrome. Still, insulin is frequently used at supraphysiological concentrations for embryo in vitro culture with unknown consequences for the developmental potential of the offspring. In the present study we investigated the effects of insulin exposure during in vitro bovine oocyte maturation on developmental rates, embryo quality and gene expression. Supplementation of the maturation media with insulin at 10 or 0.1 µg mL-1 decreased blastocyst rates compared with an insulin-free control (19.8 ± 1.3% and 20.4 ± 1.3% vs 23.8 ± 1.3%, respectively; P < 0.05) and led to increased cell numbers (nearly 10% more cells on Day 8 compared with control; P < 0.05). Transcriptome analysis revealed significant upregulation of genes involved in lipid metabolism, nuclear factor (erythroid-derived 2)-like 2 (NRF2) stress response and cell differentiation, validated by quantitative polymerase chain reaction. To conclude, the results of the present study demonstrate that insulin exposure during in vitro oocyte maturation has a lasting effect on the embryo until the blastocyst stage, with a potential negative effect in the form of specific gene expression perturbations.
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, P.O. Box 7054, SE-750 07 Uppsala, Sweden.|Corresponding author. Email: denise.laskowski@slu.se.
authors.forename: Denise
authors.initials: D
authors.lastname: Laskowski
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, P.O. Box 7054, SE-750 07 Uppsala, Sweden.
authors.forename: Ylva
authors.initials: Y
authors.lastname: Sjunnesson
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, P.O. Box 7054, SE-750 07 Uppsala, Sweden.
authors.forename: Patrice
authors.initials: P
authors.lastname: Humblot
authors.affiliation: Departement des Sciences Animales, Centre de Recherche en Biologie de la Reproduction, Pavillon Des Services, local 2732, Université Laval, Québec G1V 0A6, Canada.
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Sirard
authors.affiliation: Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, P.O. Box 7054, SE-750 07 Uppsala, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Andersson
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, P.O. Box 7054, SE-750 07 Uppsala, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Gustafsson
authors.affiliation: Department of Clinical Sciences, Swedish University of Agricultural Sciences, P.O. Box 7054, SE-750 07 Uppsala, Sweden.
authors.forename: Renée
authors.initials: R
authors.lastname: Båge
keywords: dairy cow; embryo; metabolic programming; metabolic syndrome; metabolism; morphology; subfertility; transcriptome