{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:32:23Z","timestamp":1787808743689,"version":"build-2784847793"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T00:00:00Z","timestamp":1723766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["17K11250"],"award-info":[{"award-number":["17K11250"]}]},{"name":"JSPS KAKENHI","award":["19K18679"],"award-info":[{"award-number":["19K18679"]}]},{"name":"JSPS KAKENHI","award":["20K18199"],"award-info":[{"award-number":["20K18199"]}]},{"name":"JSPS KAKENHI","award":["20K09650"],"award-info":[{"award-number":["20K09650"]}]},{"name":"JSPS KAKENHI","award":["21K09501"],"award-info":[{"award-number":["21K09501"]}]},{"name":"JSPS KAKENHI","award":["2017"],"award-info":[{"award-number":["2017"]}]},{"name":"JSPS KAKENHI","award":["2015"],"award-info":[{"award-number":["2015"]}]},{"name":"JSPS KAKENHI","award":["23E116"],"award-info":[{"award-number":["23E116"]}]},{"name":"the Shimabara Science Promotion Foundation","award":["17K11250"],"award-info":[{"award-number":["17K11250"]}]},{"name":"the Shimabara Science Promotion Foundation","award":["19K18679"],"award-info":[{"award-number":["19K18679"]}]},{"name":"the Shimabara Science Promotion Foundation","award":["20K18199"],"award-info":[{"award-number":["20K18199"]}]},{"name":"the Shimabara Science Promotion Foundation","award":["20K09650"],"award-info":[{"award-number":["20K09650"]}]},{"name":"the Shimabara Science Promotion Foundation","award":["21K09501"],"award-info":[{"award-number":["21K09501"]}]},{"name":"the Shimabara Science Promotion Foundation","award":["2017"],"award-info":[{"award-number":["2017"]}]},{"name":"the Shimabara Science Promotion Foundation","award":["2015"],"award-info":[{"award-number":["2015"]}]},{"name":"the Shimabara Science Promotion Foundation","award":["23E116"],"award-info":[{"award-number":["23E116"]}]},{"name":"the Sumitomo Foundation","award":["17K11250"],"award-info":[{"award-number":["17K11250"]}]},{"name":"the Sumitomo Foundation","award":["19K18679"],"award-info":[{"award-number":["19K18679"]}]},{"name":"the Sumitomo Foundation","award":["20K18199"],"award-info":[{"award-number":["20K18199"]}]},{"name":"the Sumitomo Foundation","award":["20K09650"],"award-info":[{"award-number":["20K09650"]}]},{"name":"the Sumitomo Foundation","award":["21K09501"],"award-info":[{"award-number":["21K09501"]}]},{"name":"the Sumitomo Foundation","award":["2017"],"award-info":[{"award-number":["2017"]}]},{"name":"the Sumitomo Foundation","award":["2015"],"award-info":[{"award-number":["2015"]}]},{"name":"the Sumitomo Foundation","award":["23E116"],"award-info":[{"award-number":["23E116"]}]},{"name":"Saitama Medical University Hospital","award":["17K11250"],"award-info":[{"award-number":["17K11250"]}]},{"name":"Saitama Medical University Hospital","award":["19K18679"],"award-info":[{"award-number":["19K18679"]}]},{"name":"Saitama Medical University Hospital","award":["20K18199"],"award-info":[{"award-number":["20K18199"]}]},{"name":"Saitama Medical University Hospital","award":["20K09650"],"award-info":[{"award-number":["20K09650"]}]},{"name":"Saitama Medical University Hospital","award":["21K09501"],"award-info":[{"award-number":["21K09501"]}]},{"name":"Saitama Medical University Hospital","award":["2017"],"award-info":[{"award-number":["2017"]}]},{"name":"Saitama Medical University Hospital","award":["2015"],"award-info":[{"award-number":["2015"]}]},{"name":"Saitama Medical University Hospital","award":["23E116"],"award-info":[{"award-number":["23E116"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Decidualization denotes the morphological and biological differentiating process of human endometrial stromal cells (HESCs). Fatty acid pathways are critical for endometrial decidualization. However, the participation of fatty acids as an energy source and their role in endometrial decidualization have received little attention. To identify fatty acids and clarify their role in decidualization, we comprehensively evaluated free fatty acid profiles using liquid chromatography\/Fourier transform mass spectrometry (LC\/FT-MS). LC\/FT-MS analysis detected 26 kinds of fatty acids in the culture medium of decidualized or un-decidualized HESCs. Only the production of octanoic acid, which is an essential energy source for embryonic development, was increased upon decidualization. The expressions of genes related to octanoic acid metabolism including ACADL, ACADM, and ACADS; genes encoding proteins catalyzing the first step of mitochondrial fatty acid beta-oxidation; and ACSL5 and ACSM5; genes encoding fatty acid synthesis proteins were significantly altered upon decidualization. These results suggest that decidualization promotes lipid metabolism, implying that decidualized HESCs require energy metabolism of the mitochondria in embryo implantation.<\/jats:p>","DOI":"10.3390\/biom14081014","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T04:29:57Z","timestamp":1723782597000},"page":"1014","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Decidualized Endometrial Stromal Cells Promote Mitochondrial Beta-Oxidation to Produce the Octanoic Acid Required for Implantation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6313-5648","authenticated-orcid":false,"given":"Yumi","family":"Mizuno","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Saitama Medical University, Iruma, Moroyama 350-0495, Saitama, Japan"},{"name":"Biomedical Research Center, Faculty of Medicine, Saitama Medical University, Iruma, Moroyama 350-0495, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7340-6931","authenticated-orcid":false,"given":"Shunsuke","family":"Tamaru","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Saitama Medical University, Iruma, Moroyama 350-0495, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideno","family":"Tochigi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Saitama Medical University, Iruma, Moroyama 350-0495, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Saitama Medical University, Iruma, Moroyama 350-0495, Saitama, Japan"},{"name":"Department of Anatomy, Saitama Medical University, Iruma, Moroyama 350-0495, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyuko","family":"Kishi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Saitama Medical University, Iruma, Moroyama 350-0495, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1147-3113","authenticated-orcid":false,"given":"Akira","family":"Ohtake","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics, Faculty of Medicine, Saitama Medical University, Iruma, Moroyama 350-0495, Saitama, Japan"},{"name":"Department of Pediatrics, Faculty of Medicine, Saitama Medical University, Iruma, Moroyama 350-0495, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Ishihara","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Saitama Medical University, Iruma, Moroyama 350-0495, Saitama, Japan"},{"name":"Nutrition Clinic, Kagawa Nutrition University, Toshima 170-8481, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Kajihara","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Saitama Medical University, Iruma, Moroyama 350-0495, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/j.placenta.2015.10.008","article-title":"Fibulin-5 is upregulated in decidualized human endometrial stromal cells and promotes primary human extravillous trophoblast outgrowth","volume":"36","author":"Winship","year":"2015","journal-title":"Placenta"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1067\/mob.2002.127305","article-title":"The myometrial junctional zone spiral arteries in normal and abnormal pregnancies: A review of the literature","volume":"187","author":"Brosens","year":"2002","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1055\/s-2007-991042","article-title":"Decidualization of the human endometrium: Mechanisms, functions, and clinical perspectives","volume":"25","author":"Gellersen","year":"2007","journal-title":"Semin. Reprod. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1210\/er.2014-1045","article-title":"Cyclic decidualization of the human endometrium in reproductive health and failure","volume":"35","author":"Gellersen","year":"2014","journal-title":"Endocr. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1177\/1933719113497280","article-title":"Androgens modulate the morphological characteristics of human endometrial stromal cells decidualized in vitro","volume":"21","author":"Kajihara","year":"2014","journal-title":"Reprod. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Gellersen, B., Wolf, A., Kruse, M., Schwenke, M., and Bamberger, A.M. (2013). Human endometrial stromal cell-trophoblast interactions: Mutual stimulation of chemotactic migration and promigratory roles of cell surface molecules CD82 and CEACAM1. Biol. Reprod., 88.","DOI":"10.1095\/biolreprod.112.106724"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Quenby, S., and Brosens, J.J. (2013). Human implantation: A tale of mutual maternal and fetal attraction. Biol. Reprod., 88.","DOI":"10.1095\/biolreprod.113.108886"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1210\/en.2008-1081","article-title":"Facilitative glucose transporter type 1 is differentially regulated by progesterone and estrogen in murine and human endometrial stromal cells","volume":"150","author":"Frolova","year":"2009","journal-title":"Endocrinology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1210\/en.2010-1266","article-title":"Quantitative analysis of glucose transporter mRNAs in endometrial stromal cells reveals critical role of GLUT1 in uterine receptivity","volume":"152","author":"Frolova","year":"2011","journal-title":"Endocrinology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3885","DOI":"10.1210\/jc.2002-021890","article-title":"Glucose transporter proteins (GLUT) in human endometrium: Expression, regulation, and function throughout the menstrual cycle and in early pregnancy","volume":"88","author":"Ursel","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0304-4157(84)90005-4","article-title":"The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function","volume":"779","author":"Stubbs","year":"1984","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1152\/physiolgenomics.00042.2015","article-title":"Endometrial gene expression in high- and low-fertility heifers in the late luteal phase of the estrous cycle and a comparison with midluteal gene expression","volume":"48","author":"Killeen","year":"2016","journal-title":"Physiol. Genom."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Killeen, A.P., Morris, D.G., Kenny, D.A., Mullen, M.P., Diskin, M.G., and Waters, S.M. (2014). Global gene expression in endometrium of high and low fertility heifers during the mid-luteal phase of the estrous cycle. BMC. Genom., 15.","DOI":"10.1186\/1471-2164-15-234"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1016\/j.bbadis.2012.05.004","article-title":"The genomics of the human endometrium","volume":"1822","author":"Blesa","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tsai, J.H., Chi, M.M., Schulte, M.B., and Moley, K.H. (2014). The fatty acid beta-oxidation pathway is important for decidualization of endometrial stromal cells in both humans and mice. Biol. Reprod., 90.","DOI":"10.1095\/biolreprod.113.113217"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Yamada, M., Takanashi, K., Hamatani, T., Hirayama, A., Akutsu, H., Fukunaga, T., Ogawa, S., Sugawara, K., Shinoda, K., and Soga, T. (2012). A medium-chain fatty acid as an alternative energy source in mouse preimplantation development. Sci. Rep., 2.","DOI":"10.1038\/srep00930"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1210\/me.2006-0118","article-title":"Differential expression of FOXO1 and FOXO3a confers resistance to oxidative cell death upon endometrial decidualization","volume":"20","author":"Kajihara","year":"2006","journal-title":"Mol. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"20825","DOI":"10.1074\/jbc.M201018200","article-title":"Cyclic AMP-induced forkhead transcription factor, FKHR, cooperates with CCAAT\/enhancer-binding protein beta in differentiating human endometrial stromal cells","volume":"277","author":"Christian","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1096\/fj.09-149153","article-title":"Silencing of the JNK pathway maintains progesterone receptor activity in decidualizing human endometrial stromal cells exposed to oxidative stress signals","volume":"24","author":"Leitao","year":"2010","journal-title":"FASEB J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.chroma.2018.11.057","article-title":"Basic eluent for rapid and comprehensive analysis of fatty acid isomers using reversed-phase high performance liquid chromatography\/Fourier transform mass spectrometry","volume":"1585","author":"Ozaki","year":"2019","journal-title":"J. Chromatogr. A"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mizuno, Y., Ninomiya, Y., Nakachi, Y., Iseki, M., Iwasa, H., Akita, M., Tsukui, T., Shimozawa, N., Ito, C., and Toshimori, K. (2013). Tysnd1 deficiency in mice interferes with the peroxisomal localization of PTS2 enzymes, causing lipid metabolic abnormalities and male infertility. PLOS Genet., 9.","DOI":"10.1371\/journal.pgen.1003286"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1006\/excr.1993.1139","article-title":"Establishment and characterization of first trimester human trophoblast cells with extended lifespan","volume":"206","author":"Graham","year":"1993","journal-title":"Exp. Cell Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1042\/bj3200345","article-title":"Mammalian mitochondrial beta-oxidation","volume":"320","author":"Eaton","year":"1996","journal-title":"Biochem. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.fertnstert.2013.03.034","article-title":"Variability in protein quality used for embryo culture: Embryotoxicity of the stabilizer octanoic acid","volume":"100","author":"Leonard","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1007\/s10815-015-0560-9","article-title":"The impact of the protein stabilizer octanoic acid on embryonic development and fetal growth in a murine model","volume":"32","author":"Fredrickson","year":"2015","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Menkhorst, E.M., Lane, N., Winship, A.L., Li, P., Yap, J., Meehan, K., Rainczuk, A., Stephens, A., and Dimitriadis, E. (2012). Decidual-secreted factors alter invasive trophoblast membrane and secreted proteins implying a role for decidual cell regulation of placentation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031418"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1095\/biolreprod.107.060558","article-title":"Polyunsaturated fatty acids in male and female reproduction","volume":"77","author":"Wathes","year":"2007","journal-title":"Biol. Reprod."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.1439-0531.2009.01402.x","article-title":"Role of fatty acids in energy provision during oocyte maturation and early embryo development","volume":"44","author":"Sturmey","year":"2009","journal-title":"Reprod. Domest. Anim."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1056\/NEJMra000763","article-title":"Implantation and the survival of early pregnancy","volume":"345","author":"Norwitz","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jnutbio.2019.03.015","article-title":"Maternal short and medium chain fatty acids supply during early pregnancy improves embryo survival through enhancing progesterone synthesis in rats","volume":"69","author":"Ye","year":"2019","journal-title":"J. Nutr. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3600","DOI":"10.1111\/cas.14606","article-title":"Caprylic acid (C8:0) promotes bone metastasis of prostate cancer by dysregulated adipo-osteogenic balance in bone marrow","volume":"111","author":"Wang","year":"2020","journal-title":"Cancer Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.fertnstert.2012.12.026","article-title":"Lipidomics as an emerging tool to predict endometrial receptivity","volume":"99","author":"Vilella","year":"2013","journal-title":"Fertil. Steril."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/8\/1014\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:37:31Z","timestamp":1760110651000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/8\/1014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,16]]},"references-count":32,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["biom14081014"],"URL":"https:\/\/doi.org\/10.3390\/biom14081014","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,16]]}}}