title: Live Births from Domestic Dog (Canis familiaris) Embryos Produced by In Vitro Fertilization.
abstract: Development of assisted reproductive technologies (ART) in the dog has resisted progress for decades, due to their unique reproductive physiology. This lack of progress is remarkable given the critical role ART could play in conserving endangered canid species or eradicating heritable disease through gene-editing technologies-an approach that would also advance the dog as a biomedical model. Over 350 heritable disorders/traits in dogs are homologous with human conditions, almost twice the number of any other species. Here we report the first live births from in vitro fertilized embryos in the dog. Adding to the practical significance, these embryos had also been cryopreserved. Changes in handling of both gametes enabled this progress. The medium previously used to capacitate sperm excluded magnesium because it delayed spontaneous acrosome exocytosis. We found that magnesium significantly enhanced sperm hyperactivation and ability to undergo physiologically-induced acrosome exocytosis, two functions essential to fertilize an egg. Unlike other mammals, dogs ovulate a primary oocyte, which reaches metaphase II on Days 4-5 after the luteinizing hormone (LH) surge. We found that only on Day 6 are oocytes consistently able to be fertilized. In vitro fertilization of Day 6 oocytes with sperm capacitated in medium supplemented with magnesium resulted in high rates of embryo development (78.8%, n = 146). Intra-oviductal transfer of nineteen cryopreserved, in vitro fertilization (IVF)-derived embryos resulted in seven live, healthy puppies. Development of IVF enables modern genetic approaches to be applied more efficiently in dogs, and for gamete rescue to conserve endangered canid species.
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.|Atkinson Center for a Sustainable Future, Cornell University, Ithaca, New York, United States of America.|Smithsonian Conservation Biology Institute, National Zoological Park, Front Royal, Virginia, United States of America.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Nagashima
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Skylar R
authors.initials: SR
authors.lastname: Sylvester
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Jacquelyn L
authors.initials: JL
authors.lastname: Nelson
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Soon Hon
authors.initials: SH
authors.lastname: Cheong
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Chinatsu
authors.initials: C
authors.lastname: Mukai
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Colleen
authors.initials: C
authors.lastname: Lambo
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: James A
authors.initials: JA
authors.lastname: Flanders
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Vicki N
authors.initials: VN
authors.lastname: Meyers-Wallen
authors.affiliation: Smithsonian Conservation Biology Institute, National Zoological Park, Front Royal, Virginia, United States of America.
authors.forename: Nucharin
authors.initials: N
authors.lastname: Songsasen
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.|Atkinson Center for a Sustainable Future, Cornell University, Ithaca, New York, United States of America.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Travis
mesh_terms: D000818:Animals; D046028:Canidae; D004285:Dogs; D004624:Embryo Transfer / Q000662:veterinary*; D047108:Embryonic Development; D056727:Endangered Species; D005260:Female; D005307:Fertilization in Vitro / Q000662:veterinary*; D050498:Live Birth; D009865:Oocytes; D011247:Pregnancy