{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T09:56:03Z","timestamp":1781690163956,"version":"3.54.5"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Funding Program for Academic Human Resources Development in Institutions of Higher Learning Under the Jurisdiction of Beijing Municipality of China"},{"name":"Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81273070"],"award-info":[{"award-number":["81273070"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"R&D Program of Beijing Municipal Education","award":["KZ202210025027"],"award-info":[{"award-number":["KZ202210025027"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Maternal obesity is known to adversely affect fetal development, with placental transcriptional dysregulation being one of the key mechanisms. However, the effect of a maternal high-fat diet (HFD) on dynamic placental gene expression, particularly in the context of obesity propensity, remains poorly understood. This study aimed to investigate the impact of a maternal HFD on time-dependent placental transcriptome alterations, with a focus on identifying key dysregulated pathways during mid-to-late gestation in rats. Female Sprague\u2013Dawley rats were fed either a HFD or control chow (CC) diet before and during pregnancy. HFD-treated rats were categorized into obese-prone (OP) and obese-resistant (OR) groups based on pre-pregnancy weight. Maternal and fetal characteristics, as well as fetal outcomes, were recorded at gestational days (GD) 14.5, 17.5, and 19.5. Plasma cytokine levels were also measured. RNA sequencing (RNA-seq) was used to compare the transcriptomes of the three groups at GD 14.5, GD 17.5, and GD 19.5. At GD 14.5, OP and OR groups showed significantly lower fetal body weight, placental weight, and efficiency compared to the CC group, with these measures increasing significantly by GD 17.5. Concurrently, RNA-seq time-series analysis revealed a significant dysregulation of the spliceosome pathway in the OR group and the parathyroid hormone synthesis pathway in the OP group during mid-to-late gestation. Specifically, 19 out of 229 annotated spliceosome genes were differentially expressed in the OR group. These transcriptomic findings were robustly validated by qPCR, which confirmed the upregulation of Sf3a1 and Sart1 in both the OR and OP groups at GD 14.5, while Sf3a2, Sf3b4, and Rbm22 were specifically elevated in the OP group. Maternal HFD disrupts placental transcriptome dynamics during mid-to-late gestation, particularly affecting spliceosome pathways, regardless of maternal obesity phenotype, contributing to placental dysfunction and adverse fetal outcomes. The observed time-dependent divergences highlight the need for phenotype- and gestational stage-specific interventions to mitigate developmental risks associated with maternal HFD.<\/jats:p>","DOI":"10.1093\/biolre\/ioag023","type":"journal-article","created":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T12:41:04Z","timestamp":1769258464000},"page":"1980-1990","source":"Crossref","is-referenced-by-count":0,"title":["Maternal high-fat diet disrupts placental spliceosome pathways independent of obesity phenotype: time-series transcriptome analysis during mid-to-late gestation in rats"],"prefix":"10.1093","volume":"114","author":[{"given":"Xiaohan","family":"Du","sequence":"first","affiliation":[{"name":"School of Public Health, Beijing Key Laboratory of Environment and Aging, Capital Medical University , Beijing Municipality 100069 ,","place":["P. R. China"]},{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Capital Medical University , Beijing Municipality 100069 ,","place":["P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Public Health, Beijing Key Laboratory of Environment and Aging, Capital Medical University , Beijing Municipality 100069 ,","place":["P. R. China"]},{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Capital Medical University , Beijing Municipality 100069 ,","place":["P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyin","family":"Le","sequence":"additional","affiliation":[{"name":"School of Public Health, Beijing Key Laboratory of Environment and Aging, Capital Medical University , Beijing Municipality 100069 ,","place":["P. R. China"]},{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Capital Medical University , Beijing Municipality 100069 ,","place":["P. R. China"]},{"name":"Department of Clinical Nutrition, China-Japan Friendship Hospital , Chaoyang District, Beijing Municipality 100029 ,","place":["P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongliang","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Beijing Key Laboratory of Environment and Aging, Capital Medical University , Beijing Municipality 100069 ,","place":["P. R. China"]},{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Capital Medical University , Beijing Municipality 100069 ,","place":["P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyang","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Public Health, Beijing Key Laboratory of Environment and Aging, Capital Medical University , Beijing Municipality 100069 ,","place":["P. R. China"]},{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Capital Medical University , Beijing Municipality 100069 ,","place":["P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanling","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Public Health, Beijing Key Laboratory of Environment and Aging, Capital Medical University , Beijing Municipality 100069 ,","place":["P. R. China"]},{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Capital Medical University , Beijing Municipality 100069 ,","place":["P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1389-6208","authenticated-orcid":false,"given":"Xiaxia","family":"Cai","sequence":"additional","affiliation":[{"name":"School of Public Health, Beijing Key Laboratory of Environment and Aging, Capital Medical University , Beijing Municipality 100069 ,","place":["P. R. China"]},{"name":"Department of Nutrition and Food Hygiene, School of Public Health, Capital Medical University , Beijing Municipality 100069 ,","place":["P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"2026061705221047000_ref1","doi-asserted-by":"publisher","first-page":"e37348","DOI":"10.1097\/MD.0000000000037348","article-title":"The causal effect of obesity on concomitant exotropia: a lifecourse Mendelian randomization study","volume":"103","author":"Liu","year":"2024","journal-title":"Medicine (Baltimore)"},{"key":"2026061705221047000_ref2","doi-asserted-by":"publisher","first-page":"3272","DOI":"10.3390\/nu12113272","article-title":"Elevated fat intake increases body weight and the risk of overweight and obesity among Chinese adults: 1991\u20132015 trends","volume":"12","author":"Wang","year":"2020","journal-title":"Nutrients"},{"key":"2026061705221047000_ref3","doi-asserted-by":"publisher","first-page":"780","DOI":"10.2337\/dc11-1790","article-title":"The hyperglycemia and adverse pregnancy outcome study: associations of GDM and obesity with pregnancy outcomes","volume":"35","author":"Catalano","year":"2012","journal-title":"Diabetes Care"},{"key":"2026061705221047000_ref4","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1111\/ppe.12125","article-title":"March of Dimes Prematurity Research Center at Stanford University School of Medicine. Maternal prepregnancy body mass index and risk of spontaneous preterm birth","volume":"28","author":"Shaw","year":"2014","journal-title":"Paediatr Perinat Epidemiol"},{"key":"2026061705221047000_ref5","doi-asserted-by":"publisher","first-page":"11255","DOI":"10.1073\/pnas.1602012113","article-title":"Maternal and fetal genomes interplay through phosphoinositol 3-kinase(PI3K)-p110\u03b1 signaling to modify placental resource allocation","volume":"113","author":"Sferruzzi-Perri","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026061705221047000_ref6","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.rbmo.2012.03.017","article-title":"Placental adaptations to the maternal-fetal environment: implications for fetal growth and developmental programming","volume":"25","author":"Sandovici","year":"2012","journal-title":"Reprod Biomed Online"},{"key":"2026061705221047000_ref7","doi-asserted-by":"publisher","first-page":"33","DOI":"10.3389\/fphys.2016.00033","article-title":"The programming power of the placenta","volume":"7","author":"Sferruzzi-Perri","year":"2016","journal-title":"Front Physiol"},{"key":"2026061705221047000_ref8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.placenta.2023.10.011","article-title":"Placental pathologic features in obesity","volume":"144","author":"Beneventi","year":"2023","journal-title":"Placenta."},{"key":"2026061705221047000_ref9","doi-asserted-by":"publisher","first-page":"2279","DOI":"10.1007\/s00404-024-07462-w","article-title":"Maternal obesity and placental function: impaired maternal-fetal axis","volume":"309","author":"Louwen","year":"2024","journal-title":"Arch Gynecol Obstet"},{"key":"2026061705221047000_ref10","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1055\/s-0034-1395584","article-title":"The status of research into resistance to diet-induced obesity","volume":"47","author":"Ding","year":"2015","journal-title":"Horm Metab Res"},{"key":"2026061705221047000_ref11","doi-asserted-by":"publisher","first-page":"1452","DOI":"10.1038\/ijo.2016.70","article-title":"The metabolic response to a high-fat diet reveals obesity-prone and -resistant phenotypes in mice with distinct mRNA-seq transcriptome profiles","volume":"40","author":"Choi","year":"2016","journal-title":"Int J Obes (Lond)"},{"key":"2026061705221047000_ref12","doi-asserted-by":"publisher","first-page":"2140","DOI":"10.1002\/oby.21620","article-title":"Obesity alters immune and metabolic profiles: new insight from obese-resistant mice on high-fat diet","volume":"24","author":"Boi","year":"2016","journal-title":"Obesity (Silver Spring)"},{"key":"2026061705221047000_ref13","doi-asserted-by":"crossref","first-page":"832","DOI":"10.3389\/fpsyg.2014.00832","article-title":"AT1 receptor blockade alters nutritional and biometric development in obesity-resistant and obesity-prone rats submitted to a high fat diet","volume":"5","author":"Smith","year":"2014","journal-title":"Front Psychol"},{"key":"2026061705221047000_ref14","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.regpep.2011.07.004","article-title":"Slower gastric emptying in high-fat diet induced obese rats is associated with attenuated plasma ghrelin and elevated plasma leptin and cholecystokinin concentrations","volume":"171","author":"Li","year":"2011","journal-title":"Regul Pept"},{"key":"2026061705221047000_ref15","doi-asserted-by":"publisher","first-page":"3928","DOI":"10.1096\/fj.13-234823","article-title":"An obesogenic diet during mouse pregnancy modifies maternal nutrient partitioning and the fetal growth trajectory","volume":"27","author":"Sferruzzi-Perri","year":"2013","journal-title":"FASEB J"},{"key":"2026061705221047000_ref16","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.lfs.2018.10.008","article-title":"Differential effects of high-fat diets before pregnancy and\/or during pregnancy on fetal growth development","volume":"212","author":"Song","year":"2018","journal-title":"Life Sci"},{"key":"2026061705221047000_ref17","doi-asserted-by":"publisher","first-page":"3111","DOI":"10.2337\/db14-1627","article-title":"Maternal high-fat feeding increases placental lipoprotein lipase activity by reducing SIRT1 expression in mice","volume":"64","author":"Qiao","year":"2015","journal-title":"Diabetes."},{"key":"2026061705221047000_ref18","doi-asserted-by":"publisher","first-page":"300","DOI":"10.4274\/jcrpe.4510","article-title":"Effect of maternal obesity on Fetal growth and expression of placental fatty acid transporters","volume":"9","author":"Ye","year":"2017","journal-title":"J Clin Res Pediatr Endocrinol"},{"key":"2026061705221047000_ref19","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.ydbio.2011.07.036","article-title":"Ablation of Tpbpa-positive trophoblast precursors leads to defects in maternal spiral artery remodeling in the mouse placenta","volume":"358","author":"Hu","year":"2011","journal-title":"Dev Biol"},{"key":"2026061705221047000_ref20","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1128\/MCB.00662-09","article-title":"The imprinted Phlda2 gene regulates extraembryonic energy stores","volume":"30","author":"Tunster","year":"2010","journal-title":"Mol Cell Biol"},{"key":"2026061705221047000_ref21","doi-asserted-by":"publisher","first-page":"3280","DOI":"10.1002\/dvdy.20981","article-title":"Origin and characteristics of glycogen cells in the developing murine placenta","volume":"235","author":"Coan","year":"2006","journal-title":"Dev Dyn"},{"key":"2026061705221047000_ref22","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1101\/gad.316034.118","article-title":"Coordinate regulation of alternative pre-mRNA splicing events by the human RNA chaperone proteins hnRNPA1 and DDX5","volume":"32","author":"Lee","year":"2018","journal-title":"Genes Dev"},{"key":"2026061705221047000_ref23","doi-asserted-by":"publisher","first-page":"e40325","DOI":"10.7554\/eLife.40325","article-title":"Splicing factors Sf3A2 and Prp31 have direct roles in mitotic chromosome segregation","volume":"7","author":"Pellacani","year":"2018","journal-title":"Elife."},{"key":"2026061705221047000_ref24","doi-asserted-by":"publisher","first-page":"2041731417712073","DOI":"10.1177\/2041731417712073","article-title":"Cellularizing hydrogel-based scaffolds to repair bone tissue: how to create a physiologically relevant micro-environment?","volume":"8","author":"Maisani","year":"2017","journal-title":"J Tissue Eng"},{"key":"2026061705221047000_ref25","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1095\/biolreprod.113.116186","article-title":"Increasing maternal body mass index is associated with systemic inflammation in the mother and the activation of distinct placental inflammatory pathways","volume":"90","author":"Aye","year":"2014","journal-title":"Biol Reprod"},{"key":"2026061705221047000_ref26","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.3389\/fphys.2018.01089","article-title":"Inflammatory determinants of Pregravid obesity in placenta and peripheral blood","volume":"9","author":"Sureshchandra","year":"2018","journal-title":"Front Physiol"},{"key":"2026061705221047000_ref27","doi-asserted-by":"publisher","first-page":"296","DOI":"10.3390\/nu12020296","article-title":"Effect of maternal obesity in mice on IL-6 levels and placental endothelial cell homeostasis","volume":"12","author":"Kretschmer","year":"2020","journal-title":"Nutrients."},{"key":"2026061705221047000_ref28","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.placenta.2010.02.002","article-title":"Maternal obesity up-regulates inflammatory signaling pathways and enhances cytokine expression in the mid-gestation sheep placenta","volume":"31","author":"Zhu","year":"2010","journal-title":"Placenta."},{"key":"2026061705221047000_ref29","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.placenta.2016.01.002","article-title":"Maternal obesity induced by a 'cafeteria' diet in the rat does not increase inflammation in maternal, placental or fetal tissues in late gestation","volume":"39","author":"Crew","year":"2016","journal-title":"Placenta."},{"key":"2026061705221047000_ref30","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1038\/s41419-021-04063-2","article-title":"Alternatively spliced ANLN isoforms synergistically contribute to the progression of head and neck squamous cell carcinoma","volume":"12","author":"Guo","year":"2021","journal-title":"Cell Death Dis"},{"key":"2026061705221047000_ref31","doi-asserted-by":"publisher","first-page":"104","DOI":"10.34763\/devperiodmed.20192302.104108","article-title":"Recent progress in human placental transcriptomics","volume":"23","author":"J\u00f3\u017awik","year":"2019","journal-title":"Dev Period Med"},{"key":"2026061705221047000_ref32","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1007\/s00439-020-02248-x","article-title":"Alternative splicing in normal and pathological human placentas is correlated to genetic variants","volume":"140","author":"Ruano","year":"2021","journal-title":"Hum Genet"},{"key":"2026061705221047000_ref33","doi-asserted-by":"publisher","first-page":"217530","DOI":"10.1016\/j.canlet.2025.217530","article-title":"Splicing factor SF3B4 acts as a switch in cancer cell senescence by regulating p21 mRNA stability","volume":"615","author":"Kang","year":"2025","journal-title":"Cancer Lett"},{"key":"2026061705221047000_ref34","doi-asserted-by":"publisher","first-page":"718","DOI":"10.14348\/molcells.2022.0037","article-title":"SF3B4 depletion retards the growth of A549 non-small cell lung cancer cells via UBE4B-mediated regulation of p53\/p21 and p27 expression","volume":"45","author":"Kim","year":"2022","journal-title":"Mol Cells"},{"key":"2026061705221047000_ref35","doi-asserted-by":"publisher","first-page":"622","DOI":"10.21873\/cgp.20478","article-title":"SF3B4 regulates cellular senescence and suppresses therapy-induced senescence of cancer cells","volume":"21","author":"Yang","year":"2024","journal-title":"Cancer Genomics Proteomics"},{"key":"2026061705221047000_ref36","doi-asserted-by":"publisher","first-page":"2367","DOI":"10.1016\/j.cmet.2021.10.016","article-title":"Nutritional reprogramming of mouse liver proteome is dampened by metformin, resveratrol, and rapamycin","volume":"33","author":"Le Couteur","year":"2021","journal-title":"Cell Metab"},{"key":"2026061705221047000_ref37","doi-asserted-by":"publisher","first-page":"23484","DOI":"10.1021\/acsomega.3c00627","article-title":"TMT Labeling reveals the effects of exercises on the proteomic characteristics of the subcutaneous adipose tissue of growing high-fat-diet-fed rats","volume":"8","author":"Song","year":"2023","journal-title":"ACS Omega"}],"container-title":["Biology of Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/biolreprod\/advance-article-pdf\/doi\/10.1093\/biolre\/ioag023\/66602087\/ioag023.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biolreprod\/article-pdf\/114\/6\/1980\/66602087\/ioag023.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biolreprod\/article-pdf\/114\/6\/1980\/66602087\/ioag023.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T09:22:25Z","timestamp":1781688145000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biolreprod\/article\/114\/6\/1980\/8442843"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":37,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,1,28]]},"published-print":{"date-parts":[[2026,6,15]]}},"URL":"https:\/\/doi.org\/10.1093\/biolre\/ioag023","relation":{},"ISSN":["0006-3363","1529-7268"],"issn-type":[{"value":"0006-3363","type":"print"},{"value":"1529-7268","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,6]]},"published":{"date-parts":[[2026,1,28]]}}}