{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T05:02:05Z","timestamp":1769835725768,"version":"3.49.0"},"reference-count":36,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AgriFutures Australia Thoroughbred Horses Program","award":["PRJ-011748"],"award-info":[{"award-number":["PRJ-011748"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Understanding the systemic biochemistry of early pregnancy in the mare is essential for developing new diagnostics and identifying causes for pregnancy loss. This study aimed to elucidate the dynamic lipidomic changes occurring during the initial stages of equine pregnancy, with a specific focus on days 7 and 14 post-ovulation. By analysing and comparing the plasma lipid profiles of pregnant and non-pregnant mares, the objective of this study was to identify potential biomarkers for pregnancy and gain insights into the biochemical adaptations essential for supporting maternal recognition of pregnancy and early embryonic development. Employing discovery lipidomics, we analysed plasma samples from pregnant and non-pregnant mares on days 7 and 14 post-conception using the SCIEX ZenoTOF 7600 system. This high-resolution mass spectrometry approach enabled us to comprehensively profile and compare the lipidomes across these critical early gestational timepoints. Our analysis revealed significant lipidomic alterations between pregnant and non-pregnant mares and between days 7 and 14 of pregnancy. Key findings include the upregulation of bile acids, sphingomyelins, phosphatidylinositols, and triglycerides in pregnant mares. These changes suggest enhanced lipid synthesis and mobilization, likely associated with the embryo\u2019s nutritional requirements and the establishment of embryo\u2013maternal interactions. There were significant differences in lipid metabolism between pregnant and non-pregnant mares, with a notable increase in the sterol lipid BA 24:1;O5 in pregnant mares as early as day 7 of gestation, suggesting it as a sensitive biomarker for early pregnancy detection. Notably, the transition from day 7 to day 14 in pregnant mares is characterized by a shift towards lipids indicative of membrane biosynthesis, signalling activity, and preparation for implantation. The study demonstrates the profound lipidomic shifts that occur in early equine pregnancy, highlighting the critical role of lipid metabolism in supporting embryonic development. These findings provide valuable insights into the metabolic adaptations during these period and potential biomarkers for early pregnancy detection in mares.<\/jats:p>","DOI":"10.3390\/ijms252011073","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T08:09:08Z","timestamp":1728979748000},"page":"11073","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Plasma Lipidomics Reveals Lipid Signatures of Early Pregnancy in Mares"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1096-7955","authenticated-orcid":false,"given":"Tharangani R. W.","family":"Perera","sequence":"first","affiliation":[{"name":"Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan 2308, Australia"},{"name":"Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights 2305, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth G.","family":"Bromfield","sequence":"additional","affiliation":[{"name":"School of BioSciences, Bio21 Institute, The University of Melbourne, Parkville 3052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zamira","family":"Gibb","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan 2308, Australia"},{"name":"Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights 2305, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2745-8188","authenticated-orcid":false,"given":"Brett","family":"Nixon","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan 2308, Australia"},{"name":"Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights 2305, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3814-9734","authenticated-orcid":false,"given":"Alecia R.","family":"Sheridan","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan 2308, Australia"},{"name":"Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights 2305, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7229-2469","authenticated-orcid":false,"given":"Thusitha","family":"Rupasinghe","sequence":"additional","affiliation":[{"name":"SCIEX, Mount Waverley 3149, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1804-1826","authenticated-orcid":false,"given":"David A.","family":"Skerrett-Byrne","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan 2308, Australia"},{"name":"Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights 2305, Australia"},{"name":"Institute of Experimental Genetics, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health, D-85764 Neuherberg, Germany"},{"name":"German Center for Diabetes Research (DZD), D-85764 Neuherberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7371-5400","authenticated-orcid":false,"given":"Aleona","family":"Swegen","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan 2308, Australia"},{"name":"Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights 2305, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/RAF-21-0104","article-title":"Conception and early pregnancy in the mare: Lipidomics the unexplored frontier","volume":"3","author":"Lawson","year":"2022","journal-title":"Reprod. Fertil."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1600433","DOI":"10.1002\/pmic.201600433","article-title":"From Peptide Masses to Pregnancy Maintenance: A Comprehensive Proteomic Analysis of The Early Equine Embryo Secretome, Blastocoel Fluid, and Capsule","volume":"17","author":"Swegen","year":"2017","journal-title":"Proteomics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1530\/jrf.0.0390145","article-title":"Direct evidence of retention of unfertilized ova in the oviduct of the mare","volume":"39","author":"Betteridge","year":"1974","journal-title":"J. Reprod. Fertil."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1095\/biolreprod.110.088732","article-title":"Transcriptional Profiling of Equine Conceptuses Reveals New Aspects of Embryo-Maternal Communication in the Horse","volume":"84","author":"Klein","year":"2011","journal-title":"Biol. Reprod."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"R139","DOI":"10.1530\/REP-20-0437","article-title":"Maternal recognition of pregnancy in the mare: Does it exist and why do we care?","volume":"161","author":"Swegen","year":"2021","journal-title":"Reproduction"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.theriogenology.2016.04.048","article-title":"Embryo-maternal communication during the first 4 weeks of equine pregnancy","volume":"86","author":"Stout","year":"2016","journal-title":"Theriogenology"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Newcombe, J.R., Cuervo-Arango, J., and Wilsher, S. (2023). The Timing of the Maternal Recognition of Pregnancy Is Specific to Individual Mares. Animals, 13.","DOI":"10.3390\/ani13101718"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1071\/RD9951275","article-title":"Fetal and maternal plasma lipids in chronically catheterized mares in late gestation: Effects of different nutritional states","volume":"7","author":"Stammers","year":"1995","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_9","first-page":"54","article-title":"Lipid and protein plasma profiles in quarter horse mares in different reproductive periods","volume":"25","year":"2014","journal-title":"Rev. Vet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"87","DOI":"10.15421\/021914","article-title":"Influence of Marmix premix on the state of lipid peroxidation and indices of non-specific resistance of the organism of pregnant mares with microelementosis","volume":"10","author":"Shcherbatyy","year":"2019","journal-title":"Regul. Mech. Biosyst."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.theriogenology.2016.04.005","article-title":"Serum levels of mitochondrial uncoupling protein 1, leptin, and lipids during late pregnancy and the early postpartum period in mares","volume":"86","author":"Arfuso","year":"2016","journal-title":"Theriogenology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s12944-023-01887-z","article-title":"LC\/MS based untargeted lipidomics reveals lipid signatures of Non-Puerperal Mastitis","volume":"22","author":"Chen","year":"2023","journal-title":"Lipids Health Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1146\/annurev-biochem-081308-165917","article-title":"Sterol Regulation of Metabolism, Homeostasis, and Development","volume":"80","author":"Wollam","year":"2011","journal-title":"Annu. Rev. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.tem.2021.09.002","article-title":"Mechanisms of lipid metabolism in uterine receptivity and embryo development","volume":"32","author":"Ye","year":"2021","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chatuphonprasert, W., Jarukamjorn, K., and Ellinger, I. (2018). Physiology and pathophysiology of steroid biosynthesis, transport and metabolism in the human placenta. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01027"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1743-7075-7-47","article-title":"Cellular cholesterol delivery, intracellular processing and utilization for biosynthesis of steroid hormones","volume":"7","author":"Hu","year":"2010","journal-title":"Nutr. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"416","DOI":"10.2741\/4216","article-title":"Physiological and pathological implications of cholesterol","volume":"19","author":"Cortes","year":"2014","journal-title":"Front. Biosci.-Landmark"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: Lessons from sphingolipids","volume":"9","author":"Hannun","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Geltinger, F., Schartel, L., Wiederstein, M., Tevini, J., Aigner, E., Felder, T.K., and Rinnerthaler, M. (2020). Friend or Foe: Lipid Droplets as Organelles for Protein and Lipid Storage in Cellular Stress Response, Aging and Disease. Molecules, 25.","DOI":"10.3390\/molecules25215053"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Howie, D., Ten Bokum, A., Necula, A.S., Cobbold, S.P., and Waldmann, H. (2018). The Role of Lipid Metabolism in T Lymphocyte Differentiation and Survival. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01949"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1172\/JCI110369","article-title":"Biliary lipids, bile acids, and gallbladder function in the human female. Effects of pregnancy and the ovulatory cycle","volume":"68","author":"Kern","year":"1981","journal-title":"J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1146\/annurev.nutr.26.061505.111156","article-title":"Choline: Critical role during fetal development and dietary requirements in adults","volume":"26","author":"Zeisel","year":"2006","journal-title":"Annu. Rev. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1111\/liv.14052","article-title":"Bile acids increase steroidogenesis in cholemic mice and induce cortisol secretion in adrenocortical H295R cells via S1PR2, ERK and SF-1","volume":"39","author":"Liu","year":"2019","journal-title":"Liver Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"104127","DOI":"10.1016\/j.jevs.2022.104127","article-title":"The Correlation of Endogenous Progesterone Concentration in Diestrus on Early Pregnancy Rate in Thoroughbred Mares","volume":"118","author":"Hollinshead","year":"2022","journal-title":"J. Equine Vet. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Aurich, C., and Budik, S. (2015). Early pregnancy in the horse revisited\u2014Does exception prove the rule?. J. Anim. Sci. Biotechnol., 6.","DOI":"10.1186\/s40104-015-0048-6"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4829180","DOI":"10.1155\/2017\/4829180","article-title":"Ethanolamine and phosphatidylethanolamine: Partners in health and disease","volume":"2017","author":"Patel","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1039\/D2MO00294A","article-title":"The dynamic inflammatory profile of pregnancy can be monitored using a novel lipid-based mass spectrometry technique","volume":"19","author":"Rees","year":"2023","journal-title":"Mol. Omics"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Miyazaki, M., and Ntambi, J.M. (2008). Fatty acid desaturation and chain elongation in mammals. Biochemistry of Lipids, Lipoproteins and Membranes, Elsevier.","DOI":"10.1016\/B978-044453219-0.50009-X"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jare.2018.01.001","article-title":"Arachidonic acid and other unsaturated fatty acids and some of their metabolites function as endogenous antimicrobial molecules: A review","volume":"11","author":"Das","year":"2018","journal-title":"J. Adv. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Hughes, C.H.K., Bosviel, R., Newman, J.W., and Pate, J.L. (2019). Luteal Lipids Regulate Progesterone Production and May Modulate Immune Cell Function During the Estrous Cycle and Pregnancy. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00662"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17003","DOI":"10.1021\/acs.analchem.2c02167","article-title":"Effect of Delayed Centrifugation on the Levels of NMR-Measured Lipoproteins and Metabolites in Plasma and Serum Samples","volume":"94","author":"Debik","year":"2022","journal-title":"Anal. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/lipd.12263","article-title":"A Review of Efforts to Improve Lipid Stability during Sample Preparation and Standardization Efforts to Ensure Accuracy in the Reporting of Lipid Measurements","volume":"56","author":"Ulmer","year":"2021","journal-title":"Lipids"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1194\/jlr.S087163","article-title":"MS-based lipidomics of human blood plasma: A community-initiated position paper to develop accepted guidelines","volume":"59","author":"Burla","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez Requena, B., Nadeem, S., Reddy, V.P., Naidoo, V., Glasgow, J.N., Steyn, A.J.C., Barbas, C., and Gonzalez-Riano, C. (2024). LiLA: Lipid lung-based ATLAS built through a comprehensive workflow designed for an accurate lipid annotation. Commun. Biol., 7.","DOI":"10.1038\/s42003-023-05680-7"},{"key":"ref_35","unstructured":"Mackenzie Pearson, S.K.K., Norris, P., and Hunter, C. (2018). Achieve Broad Lipid Quantitation Using a High-Throughput Targeted Lipidomics Method, SCIEX."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"W388","DOI":"10.1093\/nar\/gkab382","article-title":"MetaboAnalyst 5.0: Narrowing the gap between raw spectra and functional insights","volume":"49","author":"Pang","year":"2021","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/20\/11073\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:13:43Z","timestamp":1760112823000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/20\/11073"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,15]]},"references-count":36,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["ijms252011073"],"URL":"https:\/\/doi.org\/10.3390\/ijms252011073","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,15]]}}}