{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T11:07:04Z","timestamp":1781780824637,"version":"3.54.5"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"33","license":[{"start":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T00:00:00Z","timestamp":1722816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001280","name":"Horserace Betting Levy Board","doi-asserted-by":"publisher","award":["SPrj046"],"award-info":[{"award-number":["SPrj046"]}],"id":[{"id":"10.13039\/501100001280","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Thoroughbred Breeders Association","award":["TBA2019"],"award-info":[{"award-number":["TBA2019"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,8,13]]},"abstract":"<jats:p>Chromosomal abnormalities are a common cause of human miscarriage but rarely reported in any other species. As a result, there are currently inadequate animal models available to study this condition. Horses present one potential model since mares receive intense gynecological care. This allowed us to investigate the prevalence of chromosomal copy number aberrations in 256 products of conception (POC) in a naturally occurring model of pregnancy loss (PL). Triploidy (three haploid sets of chromosomes) was the most common aberration, found in 42% of POCs following PL over the embryonic period. Over the same period, trisomies and monosomies were identified in 11.6% of POCs and subchromosomal aberrations in 4.2%. Whole and subchromosomal aberrations involved 17 autosomes, with chromosomes 3, 4, and 20 having the highest number of aberrations. Triploid fetuses had clear gross developmental anomalies of the brain. Collectively, data demonstrate that alterations in chromosome number contribute to PL similarly in women and mares, with triploidy the dominant ploidy type over the key period of organogenesis. These findings, along with highly conserved synteny between human and horse chromosomes, similar gestation lengths, and the shared single greatest risk for PL being advancing maternal age, provide strong evidence for the first animal model to truly recapitulate many key features of human miscarriage arising due to chromosomal aberrations, with shared benefits for humans and equids.<\/jats:p>","DOI":"10.1073\/pnas.2405636121","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T15:05:17Z","timestamp":1722870317000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":11,"title":["Naturally occurring horse model of miscarriage reveals temporal relationship between chromosomal aberration type and point of lethality"],"prefix":"10.1073","volume":"121","author":[{"given":"Jessica M.","family":"Lawson","sequence":"first","affiliation":[{"name":"Department of Pathobiology and Population Sciences, Royal Veterinary College, London AL9 7TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5315-8934","authenticated-orcid":false,"given":"Shebl E.","family":"Salem","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4868-1007","authenticated-orcid":false,"given":"Donald","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Kahler","sequence":"additional","affiliation":[{"name":"Department of Pathobiology and Population Sciences, Royal Veterinary College, London AL9 7TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelmina J.","family":"van den Boer","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte A.","family":"Shilton","sequence":"additional","affiliation":[{"name":"Department of Pathobiology and Population Sciences, Royal Veterinary College, London AL9 7TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tia","family":"Sever","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9850-7878","authenticated-orcid":false,"given":"Rebecca R.","family":"Mouncey","sequence":"additional","affiliation":[{"name":"Department of Pathobiology and Population Sciences, Royal Veterinary College, London AL9 7TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Hampshire","sequence":"additional","affiliation":[{"name":"Department of Pathobiology and Population Sciences, Royal Veterinary College, London AL9 7TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alastair K.","family":"Foote","sequence":"additional","affiliation":[{"name":"Rossdales Laboratories, Rossdales Ltd, Beaufort Cottages Stables, Newmarket CB8 8JS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill S.","family":"Bryan","sequence":"additional","affiliation":[{"name":"Rossdales Laboratories, Rossdales Ltd, Beaufort Cottages Stables, Newmarket CB8 8JS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7385-0618","authenticated-orcid":false,"given":"Rytis","family":"Juras","sequence":"additional","affiliation":[{"name":"Department of Veterinary Integrative Biosciences, Texas A&amp;M University, College Station, TX 77843"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver D.","family":"Pynn","sequence":"additional","affiliation":[{"name":"Rossdales Veterinary Surgeons, Rossdales Ltd, Beaufort Cottages Stables, Newmarket CB8 8JS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6121-135X","authenticated-orcid":false,"given":"Brian W.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Veterinary Integrative Biosciences, Texas A&amp;M University, College Station, TX 77843"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca R.","family":"Bellone","sequence":"additional","affiliation":[{"name":"Department of Population Health and Reproduction, Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, CA 95617"},{"name":"Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95617"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2276-475X","authenticated-orcid":false,"given":"Terje","family":"Raudsepp","sequence":"additional","affiliation":[{"name":"Department of Veterinary Integrative Biosciences, Texas A&amp;M University, College Station, TX 77843"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9422-2370","authenticated-orcid":false,"given":"Amanda M.","family":"de Mestre","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,8,5]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00682-6"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02645-5"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.545856"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00517-3"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm243"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/104063879600800114"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-69967-z"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02687-9"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.934543"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-021-09930-z"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1071\/RD22239"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2015.12.014"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1159\/000523715"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-019-01415-y"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/evj.13340"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2018.12.042"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.3390\/ani11030831"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.2746\/042516402776181240"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-013-9450-6"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-3306.1989.tb02092.x"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-3306.1999.tb03796.x"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-3306.1997.tb01638.x"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.104159"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwh332"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2021.103195"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav7321"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.200391"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-48103-7"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.037747"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10577-010-9181-4"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14003"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63107"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200572"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10754"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1178158"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-018-0199-z"},{"key":"e_1_3_4_37_2","unstructured":"R Core Team R: A language and environment for statistical computing (R Foundation for Statistical Computing Vienna Austria 2024)."},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx346"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-58592-5_14"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2052.2010.02101.x"},{"key":"e_1_3_4_41_2","unstructured":"J. M. Lawson deMestre-lab\/Pregnancy-Loss-Genetics-PNAS. Zenodo. https:\/\/zenodo.org\/doi\/10.5281\/zenodo.12745505. Deposited 15 July 2024."},{"key":"e_1_3_4_42_2","unstructured":"J. M. Lawson GGP equine intensity files. Zenodo. https:\/\/zenodo.org\/doi\/10.5281\/zenodo.12746246. Deposited 15 July 2024."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2405636121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T15:07:36Z","timestamp":1722870456000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2405636121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,5]]},"references-count":42,"journal-issue":{"issue":"33","published-print":{"date-parts":[[2024,8,13]]}},"alternative-id":["10.1073\/pnas.2405636121"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2405636121","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,5]]},"assertion":[{"value":"2024-04-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2405636121"}}