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Postpartum lactational peak and reduced feed intake lead to negative energy balance in cattle. As a compensatory mechanism, cattle start mobilizing fat reserves to meet the energy demand for vital body functions. Consequently, diminished glucose concentrations and elevated ketone body levels lead to poor ovarian function. The impaired follicular development and subpar oocyte quality diminish the conception rates, which poses significant economic repercussions. Follicular fluid is integral to the processes of follicular growth and oocyte development. Hence, the present study was performed to identify potential alterations in metabolites in the follicular fluid under in vitro culture conditions mimicking negative energy balance. Our results revealed nine distinct metabolites exhibiting differential expression in follicular fluid under negative energy balance. The differentially expressed metabolites were predominantly associated with pathways related to amino acid metabolism, lipid metabolism, signal transduction mechanisms, and membrane transport, alongside other biological processes. The identified signature metabolites may be further validated to determine oocyte fitness subjected to in vitro fertilization or embryo production from slaughterhouse source ovaries.<\/jats:p>","DOI":"10.3390\/ijms252312629","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T03:59:01Z","timestamp":1732507141000},"page":"12629","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Unravelling the Signature Follicular Fluid Metabolites in Dairy Cattle Follicles Growing Under Negative Energy Balance: An In Vitro Approach"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8615-7516","authenticated-orcid":false,"given":"Muhammad","family":"Shahzad","sequence":"first","affiliation":[{"name":"Institute of Animal Sciences (IAS), Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan Western Road, Haidian District, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Cao","sequence":"additional","affiliation":[{"name":"Institute of Animal Sciences (IAS), Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan Western Road, Haidian District, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubdar Ali","family":"Kolachi","sequence":"additional","affiliation":[{"name":"Institute of Animal Sciences (IAS), Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan Western Road, Haidian District, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4910-151X","authenticated-orcid":false,"given":"Jesse Oluwaseun","family":"Ayantoye","sequence":"additional","affiliation":[{"name":"Institute of Animal Sciences (IAS), Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan Western Road, Haidian District, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Animal Sciences (IAS), Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan Western Road, Haidian District, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Niu","sequence":"additional","affiliation":[{"name":"Institute of Animal Sciences (IAS), Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan Western Road, Haidian District, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengcheng","family":"Wan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Sheep Genetic Improvement and Healthy Breeding, Institute of Animal Husbandry and Veterinary Sciences, Xinjiang Academy of Agricultural and Reclamation Sciences, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Animal Sciences (IAS), Chinese Academy of Agricultural Sciences (CAAS), No. 2 Yuanmingyuan Western Road, Haidian District, Beijing 100193, China"},{"name":"State Key Laboratory of Sheep Genetic Improvement and Healthy Breeding, Institute of Animal Husbandry and Veterinary Sciences, Xinjiang Academy of Agricultural and Reclamation Sciences, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100292","DOI":"10.1016\/j.animal.2021.100292","article-title":"Genetic selection of high-yielding dairy cattle toward sustainable farming systems in a rapidly changing world","volume":"15","author":"Brito","year":"2021","journal-title":"Animal"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gutierrez-Reinoso, M.A., Aponte, P.M., and Garcia-Herreros, M. (2021). Genomic analysis, progress and future perspectives in dairy cattle selection: A review. Animals, 11.","DOI":"10.3390\/ani11030599"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.3168\/jds.2021-21483","article-title":"Trend analysis and prediction of seasonal changes in milk composition from a pasture-based dairy research herd","volume":"106","author":"Hayes","year":"2023","journal-title":"J. Dairy Sci."},{"key":"ref_4","unstructured":"(2024, September 19). USDA Development of the Average Annual Milk Production Per Cow in the United States Since 1924, Available online: https:\/\/quickstats.nass.usda.gov\/."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1093\/af\/vfad014","article-title":"Dairy cow physiology and production limits","volume":"13","author":"Gross","year":"2023","journal-title":"Anim. Front. Rev. Mag. Anim. Agric."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhao, C., Shu, S., Bai, Y., Wang, D., Xia, C., and Xu, C. (2019). Plasma protein comparison between dairy cows with inactive ovaries and estrus. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-49785-8"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Bai, Y., Zhang, F., Zhang, H., Xu, C., Wu, L., and Xia, C. (2020). Follicular fluid metabolite changes in dairy cows with inactive ovary identified using untargeted metabolomics. BioMed Res. Int., 2020.","DOI":"10.1155\/2020\/9837543"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"288","DOI":"10.3168\/jdsc.2022-0354","article-title":"Effects of pathogen-specific clinical mastitis occurrence in the first 100 days of lactation 1 on future mastitis occurrence in Holstein dairy cows: An observational study","volume":"4","author":"Hertl","year":"2023","journal-title":"JDS Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1590\/1678-4162-11659","article-title":"Nutritional, behavioral and performance parameters of F1 Holstein x Zebu cows at different lactation stages","volume":"72","author":"Santana","year":"2020","journal-title":"Arq. Bras. Med. Veterin\u00e1ria E Zootec."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10353","DOI":"10.3168\/jds.2017-13242","article-title":"A 100-Year Review: Regulation of nutrient partitioning to support lactation","volume":"100","author":"Baumgard","year":"2017","journal-title":"J. Dairy Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lin, Y., Sun, X., Hou, X., Qu, B., Gao, X., and Li, Q. (2016). Effects of glucose on lactose synthesis in mammary epithelial cells from dairy cow. BMC Vet. Res., 12.","DOI":"10.1186\/s12917-016-0704-x"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Habel, J., and Sundrum, A. (2020). Mismatch of glucose allocation between different life functions in the transition period of dairy cows. Animals, 10.","DOI":"10.3390\/ani10061028"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Brandstetter, V., Neubauer, V., Humer, E., Kr\u00f6ger, I., and Zebeli, Q. (2019). Chewing and drinking activity during transition period and lactation in dairy cows fed partial mixed rations. Animals, 9.","DOI":"10.3390\/ani9121088"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"602","DOI":"10.3168\/jds.2020-18883","article-title":"Differential gene expression in dairy cows under negative energy balance and ketosis: A systematic review and meta-analysis","volume":"104","author":"Soares","year":"2021","journal-title":"J. Dairy Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Omari, M., Lange, A., Pl\u00f6ntzke, J., and R\u00f6blitz, S. (2020). Model-based exploration of the impact of glucose metabolism on the estrous cycle dynamics in dairy cows. Biol. Direct, 15.","DOI":"10.1186\/s13062-019-0256-7"},{"key":"ref_16","first-page":"55","article-title":"Roles of glucagon and insulin in the regulation of metabolism in ruminants. A review","volume":"19","author":"Brockman","year":"1978","journal-title":"Can. Vet. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"361","DOI":"10.2478\/jvetres-2021-0035","article-title":"Effect of negative energy balance on plasma metabolites, minerals, hormones, cytokines and ovarian follicular growth rate in Holstein dairy cows","volume":"65","author":"Song","year":"2021","journal-title":"J. Vet. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tessari, R., Berlanda, M., Morgante, M., Badon, T., Gianesella, M., Mazzotta, E., Contiero, B., and Fiore, E. (2020). Changes of plasma fatty acids in four lipid classes to understand energy metabolism at different levels of non-esterified fatty acid (NEFA) in dairy cows. Animals, 10.","DOI":"10.3390\/ani10081410"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.rvsc.2022.01.003","article-title":"Global prevalence of subclinical ketosis in dairy cows: A systematic review and meta-analysis","volume":"144","author":"Loiklung","year":"2022","journal-title":"Res. Vet. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Serbetci, I., Gonz\u00e1lez-Grajales, L.A., Herrera, C., Ibanescu, I., Tekin, M., Melean, M., Magata, F., Malama, E., Bollwein, H., and Scarlet, D. (2024). Impact of negative energy balance and postpartum diseases during the transition period on oocyte quality and embryonic development in dairy cows. Front. Vet. Sci., 10.","DOI":"10.3389\/fvets.2023.1328700"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Paes, V.M., de Figueiredo, J.R., Ryan, P.L., Willard, S.T., and Feugang, J.M. (2020). Comparative analysis of porcine follicular fluid proteomes of small and large ovarian follicles. Biology, 9.","DOI":"10.3390\/biology9050101"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Guerreiro, T.M., Gon\u00e7alves, R.F., Melo, C.F.O.R., De Oliveira, D.N., Lima, E.d.O., Visintin, J.A., De Achilles, M.A., and Catharino, R.R. (2018). A metabolomic overview of follicular fluid in cows. Front. Vet. Sci., 5.","DOI":"10.3389\/fvets.2018.00010"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s10815-018-1143-3","article-title":"Influence of follicular fluid and cumulus cells on oocyte quality: Clinical implications","volume":"35","author":"Giorgi","year":"2018","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0378-4320(03)00173-8","article-title":"Metabolite and ionic composition of follicular fluid from different-sized follicles and their relationship to serum concentrations in dairy cows","volume":"80","author":"Leroy","year":"2004","journal-title":"Anim. Reprod. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/j.1439-0531.2006.00650.x","article-title":"The in vitro development of bovine oocytes after maturation in glucose and \u03b2-hydroxybutyrate concentrations associated with negative energy balance in dairy cows","volume":"41","author":"Leroy","year":"2006","journal-title":"Reprod. Domest. Anim."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Wang, Z., Song, Y., Sun, S., Zhao, C., Fu, S., Xia, C., and Bai, Y. (2022). Metabolite Comparison between serum and follicular fluid of dairy cows with inactive ovaries postpartum. Animals, 12.","DOI":"10.3390\/ani12030285"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Aguila, L., Treulen, F., Therrien, J., Felmer, R., Valdivia, M., and Smith, L.C. (2020). Oocyte selection for in vitro embryo production in bovine species: Noninvasive approaches for new challenges of oocyte competence. Animals, 10.","DOI":"10.20944\/preprints202010.0453.v2"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"100039","DOI":"10.1016\/j.meomic.2024.100039","article-title":"The omics technologies and liquid biopsies: Advantages, limitations, applications","volume":"11","author":"Magro","year":"2024","journal-title":"Med. Omics"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Furlani, I.L., da Cruz Nunes, E., Canuto, G.A., Macedo, A.N., and Oliveira, R.V. (2021). Liquid chromatography-mass spectrometry for clinical metabolomics: An overview. Separation Techniques Applied to Omics Sciences: From Principles to Relevant Application, Springer.","DOI":"10.1007\/978-3-030-77252-9_10"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/s41392-023-01399-3","article-title":"Small molecule metabolites: Discovery of biomarkers and therapeutic targets","volume":"8","author":"Qiu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Phillips, K.M., Read, C.C., Kriese-Anderson, L.A., Rodning, S.P., Brandebourg, T.D., Biase, F.H., Marks, M.L., Elmore, J.B., Stanford, M.K., and Dyce, P.W. (2018). Plasma metabolomic profiles differ at the time of artificial insemination based on pregnancy outcome, in Bos taurus beef heifers. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-31605-0"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Yang, J., Li, Y., Li, S., Zhang, Y., Feng, R., Huang, R., Chen, M., and Qian, Y. (2022). Metabolic signatures in human follicular fluid identify lysophosphatidylcholine as a predictor of follicular development. Commun. Biol., 5.","DOI":"10.1038\/s42003-022-03710-4"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1071\/RD14348","article-title":"Lactation-induced changes in metabolic status and follicular-fluid metabolomic profile in postpartum dairy cows","volume":"28","author":"Forde","year":"2016","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1530\/REP-20-0047","article-title":"Proteomics and metabolomics in cow fertility: A systematic review","volume":"160","author":"Aranciaga","year":"2020","journal-title":"Reproduction"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Islam, M.A., Adachi, S., Shiiba, Y., Takeda, K.-i., Haga, S., and Yonekura, S. (2022). Effects of starvation-induced negative energy balance on endoplasmic reticulum stress in the liver of cows. Anim. Biosci., 35.","DOI":"10.5713\/ab.21.0140"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Calder, P.C. (2024). Dietary fatty acids, lipid mediators, immunity, and inflammation. Functional Dietary Lipids, Elsevier.","DOI":"10.1016\/B978-0-443-15327-3.00003-3"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1079\/PNS19980042","article-title":"Modulation of immune function by dietary fatty acids","volume":"57","author":"Miles","year":"1998","journal-title":"Proc. Nutr. Soc."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Teng, Z., Wang, L., Du, H., Yang, G., Fu, T., Lian, H., Sun, Y., Liu, S., Zhang, L., and Gao, T. (2021). Metabolomic and lipidomic approaches to evaluate the effects of Eucommia ulmoides leaves on milk quality and biochemical properties. Front. Vet. Sci., 8.","DOI":"10.3389\/fvets.2021.644967"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Banerjee, J., Sharma, R., Agarwal, A., Maitra, D., Diamond, M.P., and Abu-Soud, H.M. (2012). IL-6 and mouse oocyte spindle. PLoS ONE, 7.","DOI":"10.1371\/annotation\/947afede-1969-4061-a535-164655e9de72"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.theriogenology.2017.04.033","article-title":"Altered expression of cytokines IL-1\u03b1, IL-6, IL-8 and TNF-\u03b1 in bovine follicular persistence","volume":"97","author":"Stassi","year":"2017","journal-title":"Theriogenology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"deae132","DOI":"10.1093\/humrep\/deae132","article-title":"Unveiling the role of chronic inflammation in ovarian aging: Insights into mechanisms and clinical implications","volume":"39","author":"Zeng","year":"2024","journal-title":"Hum. Reprod."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s00277-005-0008-x","article-title":"Decitabine: A historical review of the development of an epigenetic drug","volume":"84","year":"2005","journal-title":"Ann. Hematol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ligasov\u00e1, A., Piskl\u00e1kov\u00e1, B., Friedeck\u00fd, D., and Koberna, K. (2023). A new technique for the analysis of metabolic pathways of cytidine analogues and cytidine deaminase activities in cells. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-47792-4"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1126\/science.167.3920.1003","article-title":"Alanine: Key role in gluconeogenesis","volume":"167","author":"Felig","year":"1970","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Zhang, X., Yang, S., Chen, J., and Su, Z. (2019). Unraveling the regulation of hepatic gluconeogenesis. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00802"},{"key":"ref_46","unstructured":"Reynolds, C. (2005). Glucose balance in cattle. Florida Ruminant Nutrition Symposium, 2005, The Ohio State University."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.theriogenology.2023.05.016","article-title":"The relationship between bovine blastocyst formation in vitro and follicular fluid amino acids","volume":"206","author":"Sanei","year":"2023","journal-title":"Theriogenology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/S1472-6483(10)60153-8","article-title":"Amino acid and fatty acid composition of follicular fluid as predictors of in-vitro embryo development","volume":"16","author":"Sinclair","year":"2008","journal-title":"Reprod. Biomed. Online"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"899","DOI":"10.21451\/1984-3143-AR2018-0017","article-title":"Influences of nutrition and metabolism on reproduction of the female ruminant","volume":"15","author":"Meikle","year":"2018","journal-title":"Anim. Reprod."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Muccini, A.M., Tran, N.T., de Guingand, D.L., Philip, M., Della Gatta, P.A., Galinsky, R., Sherman, L.S., Kelleher, M.A., Palmer, K.R., and Berry, M.J. (2021). Creatine metabolism in female reproduction, pregnancy and newborn health. Nutrients, 13.","DOI":"10.3390\/nu13020490"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ravisankar, S., Hanna, C.B., Brooks, K.E., Murphy, M.J., Redmayne, N., Ryu, J., Kinchen, J.M., Chavez, S.L., and Hennebold, J.D. (2021). Metabolomics analysis of follicular fluid coupled with oocyte aspiration reveals importance of glucocorticoids in primate periovulatory follicle competency. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-85704-6"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"G113","DOI":"10.1152\/ajpgi.00143.2021","article-title":"Contribution of monocarboxylate transporter 12 to blood supply of creatine on the sinusoidal membrane of the hepatocytes","volume":"321","author":"Jomura","year":"2021","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Uhde, K., van Tol, H.T., Stout, T.A., and Roelen, B.A. (2018). Metabolomic profiles of bovine cumulus cells and cumulus-oocyte-complex-conditioned medium during maturation in vitro. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-27829-9"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/S0015-0282(16)49839-0","article-title":"Enhancement of human sperm motility and velocity in vitro: Effects of calcium and creatine phosphate","volume":"46","author":"Fakih","year":"1986","journal-title":"Fertil. Steril."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1080\/09712119.2023.2176859","article-title":"Negative energy balance and its implication on productive and reproductive performance of early lactating dairy cows","volume":"51","author":"Mekuriaw","year":"2023","journal-title":"J. Appl. Anim. Res."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Velasquez, M.T., Ramezani, A., Manal, A., and Raj, D.S. (2016). Trimethylamine N-oxide: The good, the bad and the unknown. Toxins, 8.","DOI":"10.3390\/toxins8110326"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Shanmugham, M., Bellanger, S., and Leo, C.H. (2023). Gut-derived metabolite, trimethylamine-N-oxide (TMAO) in cardio-metabolic diseases: Detection, mechanism, and potential therapeutics. Pharmaceuticals, 16.","DOI":"10.3390\/ph16040504"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cbpb.2005.03.004","article-title":"A comparison of the counteracting effects of glycine betaine and TMAO on the activity of RNase A in aqueous urea solution","volume":"141","author":"Samuelsson","year":"2005","journal-title":"Comp. Biochem. Physiol. Part A Mol. Integr. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Wu, Z.-L., Chen, S.-Y., Hu, S., Jia, X., Wang, J., and Lai, S.-J. (2020). Metabolomic and proteomic profiles associated with ketosis in dairy cows. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.551587"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"106268","DOI":"10.1016\/j.anireprosci.2019.106268","article-title":"Alpine and lowland grazing differentially alter the reproductive tract redox milieu and amino acid composition in cattle","volume":"213","author":"Chiumia","year":"2020","journal-title":"Anim. Reprod. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1017\/S0967199423000588","article-title":"Structural and metabolic cumulus cell alteration affects oocyte quality in underweight women","volume":"32","author":"Ji","year":"2024","journal-title":"Zygote"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/humrep\/dez224","article-title":"Trimethylamine-N-oxide is present in human follicular fluid and is a negative predictor of embryo quality","volume":"35","author":"Nagy","year":"2020","journal-title":"Hum. Reprod."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/s12964-024-01540-x","article-title":"Metabolism of asparagine in the physiological state and cancer","volume":"22","author":"Yuan","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.1093\/humrep\/13.12.3441","article-title":"Intracellular pH of the mouse preimplantation embryo: Amino acids act as buffers of intracellular pH","volume":"13","author":"Edwards","year":"1998","journal-title":"Hum. Reprod."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2000531","DOI":"10.1002\/advs.202000531","article-title":"DPAGT1-Mediated Protein N-Glycosylation Is Indispensable for Oocyte and Follicle Development in Mice","volume":"7","author":"Li","year":"2020","journal-title":"Adv. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.neuron.2013.08.013","article-title":"Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy","volume":"80","author":"Ruzzo","year":"2013","journal-title":"Neuron"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Moran, B., Cummins, S.B., Creevey, C.J., and Butler, S.T. (2016). Transcriptomics of liver and muscle in Holstein cows genetically divergent for fertility highlight differences in nutrient partitioning and inflammation processes. BMC Genom., 17.","DOI":"10.1186\/s12864-016-2938-1"},{"key":"ref_68","first-page":"pgae181","article-title":"Impact of preovulatory follicle maturity on oocyte metabolism and embryo development","volume":"3","author":"Clark","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA Nexus"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6354","DOI":"10.3168\/jds.2019-17916","article-title":"Heritability estimates of predicted blood \u03b2-hydroxybutyrate and nonesterified fatty acids and relationships with milk traits in early-lactation Holstein cows","volume":"103","author":"Benedet","year":"2020","journal-title":"J. Dairy Sci."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Zhang, K.-Y., Guo, J., Zhan, C.-L., Yuan, C.-S., Min, C.-G., Li, Z.-Q., Liu, H.-Y., Wang, J., Zhao, J., and Lu, W.-F. (2023). \u03b2-hydroxybutyrate impairs bovine oocyte maturation via pyruvate dehydrogenase (PDH) associated energy metabolism abnormality. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1243243"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s12192-017-0846-1","article-title":"Nutritional and metabolic stressors on ovine oocyte development and granulosa cell functions in vitro","volume":"23","author":"Nandi","year":"2018","journal-title":"Cell Stress Chaperones"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"txad084","DOI":"10.1093\/tas\/txad084","article-title":"Evaluation of a ruminally protected blend of pantothenic acid, pyridoxine, folic acid, biotin, and vitamin B12 on finishing steer growth performance, efficiency of dietary net energy utilization, carcass trait responses, and liver abscess prevalence and severity","volume":"7","author":"Ribeiro","year":"2023","journal-title":"Transl. Anim. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/j.1439-0396.2010.01004.x","article-title":"Pantothenic acid in ruminant nutrition: A review","volume":"95","author":"Ragaller","year":"2011","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Li, J., Zhang, Z., Wei, Y., Zhu, P., Yin, T., and Wan, Q. (2023). Metabonomic analysis of follicular fluid in patients with diminished ovarian reserve. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1132621"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev-nutr-071816-064916","article-title":"\u03b2-Hydroxybutyrate: A signaling metabolite","volume":"37","author":"Newman","year":"2017","journal-title":"Annu. Rev. Nutr."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"10-1128","DOI":"10.1128\/ecosalplus.3.6.3.4","article-title":"Biosynthesis of pantothenic acid and coenzyme A","volume":"2","author":"Leonardi","year":"2007","journal-title":"EcoSal Plus"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ymben.2020.03.008","article-title":"Transient vitamin B5 starving improves mammalian cell homeostasis and protein production","volume":"60","author":"Pourcel","year":"2020","journal-title":"Metab. Eng."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Read, C.C., Edwards, L., Schrick, N., Rhinehart, J.D., Payton, R.R., Campagna, S.R., Castro, H.F., Klabnik, J.L., Horn, E.J., and Moorey, S.E. (2021). Correlation between pre-ovulatory follicle diameter and follicular fluid metabolome profiles in lactating beef cows. Metabolites, 11.","DOI":"10.3390\/metabo11090623"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Chen, Y., Yang, J., and Zhang, L. (2023). The Impact of Follicular Fluid Oxidative Stress Levels on the Outcomes of Assisted Reproductive Therapy. Antioxidants, 12.","DOI":"10.3390\/antiox12122117"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Kurdi, C., Lelovics, V., Hesszenberger, D., Lajtai, A., Lakatos, \u00c1., Herczeg, R., G\u00f6d\u00f6ny, K., Mauchart, P., V\u00e1rnagy, \u00c1., and Kov\u00e1cs, G.L. (2023). Amino Acid Profiling of Follicular Fluid in Assisted Reproduction Reveals Important Roles of Several Amino Acids in Patients with Insulin Resistance. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202307.0838.v1"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4639","DOI":"10.3168\/jds.2018-15601","article-title":"Plasma metabolite changes in dairy cows during parturition identified using untargeted metabolomics","volume":"102","author":"Luo","year":"2019","journal-title":"J. Dairy Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1080\/1828051X.2016.1180643","article-title":"Pathway analysis of plasma different metabolites for dairy cow ketosis","volume":"15","author":"Wang","year":"2016","journal-title":"Ital. J. Anim. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4795","DOI":"10.3168\/jds.2019-17777","article-title":"Relationship between energy balance and metabolic profiles in plasma and milk of dairy cows in early lactation","volume":"103","author":"Xu","year":"2020","journal-title":"J. Dairy Sci."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Lisuzzo, A., Laghi, L., Faillace, V., Zhu, C., Contiero, B., Morgante, M., Mazzotta, E., Gianesella, M., and Fiore, E. (2022). Differences in the serum metabolome profile of dairy cows according to the BHB concentration revealed by proton nuclear magnetic resonance spectroscopy (1H-NMR). Sci. Rep., 12.","DOI":"10.1038\/s41598-022-06507-x"},{"key":"ref_85","first-page":"100175","article-title":"Exploring the medicinal significance of l-Arginine mediated nitric oxide in preventing health disorders","volume":"12","author":"Oyovwi","year":"2024","journal-title":"Eur. J. Med. Chem. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Luo, Y., Zhu, Y., Basang, W., Wang, X., Li, C., and Zhou, X. (2021). Roles of nitric oxide in the regulation of reproduction: A review. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.752410"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S0015-0282(02)04823-9","article-title":"Effects of nitric oxide and cGMP on inhibin A and inhibin subunit mRNA levels from cultured rat granulosa cells","volume":"79","author":"Chen","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.nutres.2020.08.008","article-title":"Beneficial effect of l-arginine in women using assisted reproductive technologies: A small-scale randomized controlled trial","volume":"82","author":"So","year":"2020","journal-title":"Nutr. Res."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Bodis, J., Farkas, B., Nagy, B., Kovacs, K., and Sulyok, E. (2022). The role of L-arginine-NO system in female reproduction: A narrative review. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314908"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.3945\/jn.117.256404","article-title":"Proline precursors and collagen synthesis: Biochemical challenges of nutrient supplementation and wound healing","volume":"147","author":"Albaugh","year":"2017","journal-title":"J. Nutr."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Parkes, W.S., Amargant, F., Zhou, L.T., Villanueva, C.E., Duncan, F.E., and Pritchard, M.T. (2021). Hyaluronan and collagen are prominent extracellular matrix components in bovine and porcine ovaries. Genes, 12.","DOI":"10.3390\/genes12081186"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1002\/mrd.20580","article-title":"Remodeling of extracellular matrix at ovulation of the bovine ovarian follicle","volume":"73","author":"Catanzariti","year":"2006","journal-title":"Mol. Reprod. Dev."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Zhu, X., Zhao, S., Xu, S., Zhang, D., Zhu, M., Pan, Q., and Huang, J. (2022). Granulosa cells improved mare oocyte cytoplasmic maturation by providing collagens. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.914735"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1002\/term.3228","article-title":"In vitro maturation using an agarose matrix with incorporated extracellular matrix proteins improves porcine oocyte developmental competence by enhancing cytoplasmic maturation","volume":"15","author":"Park","year":"2021","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Joo, S., Oh, S.-H., Sittadjody, S., Opara, E.C., Jackson, J.D., Lee, S.J., Yoo, J.J., and Atala, A. (2016). The effect of collagen hydrogel on 3D culture of ovarian follicles. Biomed. Mater., 11.","DOI":"10.1088\/1748-6041\/11\/6\/065009"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1439-0531.2006.00639.x","article-title":"Meiotic competence of canine oocytes embedded in collagen gel","volume":"41","author":"Otoi","year":"2006","journal-title":"Reprod. Domest. Anim."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Liu, Z., Jiang, A., Lv, X., Fan, D., Chen, Q., Wu, Y., Zhou, C., and Tan, Z. (2024). Combined Metabolomics and Biochemical Analyses of Serum and Milk Revealed Parity-Related Metabolic Differences in Sanhe Dairy Cattle. Metabolites, 14.","DOI":"10.3390\/metabo14040227"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Barbato, V., Genovese, V., De Gregorio, V., Di Nardo, M., Travaglione, A., De Napoli, L., Fragomeni, G., Zanetti, E.M., Adiga, S.K., and Mondrone, G. (2023). Dynamic in vitro culture of bovine and human ovarian tissue enhances follicle progression and health. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-37086-0"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Siu, M.K., and Cheng, C.Y. (2013). The blood-follicle barrier (BFB) in disease and in ovarian function. Biology and Regulation of Blood-Tissue Barriers, Springer.","DOI":"10.1007\/978-1-4614-4711-5_9"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Wen, X., Zhou, J., Yue, S., Zhang, J., Chen, Y., Wang, Z., Wang, L., Peng, Q., and Xue, B. (2024). Establishment of an immortalized yak granulosa cell line: In vitro tool for understanding the molecular processes of ovarian follicle development. Front. Vet. Sci., 11.","DOI":"10.3389\/fvets.2024.1362502"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1080\/1828051X.2021.1899855","article-title":"Follicular fluid proteomic profiling of dairy cows with anestrus caused by negative energy balance","volume":"20","author":"Zhao","year":"2021","journal-title":"Ital. J. Anim. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e20180935","DOI":"10.1590\/0001-3765202020180935","article-title":"Comparison of bovine small antral follicle development in two-and three-dimensional culture systems","volume":"92","author":"He","year":"2020","journal-title":"An. Acad. Bras. Ci\u00eancias"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1262\/jrd.2013-086","article-title":"Multifactorial analysis of the follicular environment is predictive of oocyte morphology in cattle","volume":"60","author":"Warzych","year":"2014","journal-title":"J. Reprod. Dev."},{"key":"ref_104","unstructured":"(2024, November 01). ProteoWizard. Available online: https:\/\/proteowizard.sourceforge.io\/download.html."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/23\/12629\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:38:45Z","timestamp":1760114325000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/23\/12629"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,25]]},"references-count":104,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ijms252312629"],"URL":"https:\/\/doi.org\/10.3390\/ijms252312629","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,25]]}}}