{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:05:04Z","timestamp":1790485504118,"version":"4.1.0"},"reference-count":155,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Biotechnology and Biological Sciences Research Council, UK","award":["BB\/F007450\/1"],"award-info":[{"award-number":["BB\/F007450\/1"]}]},{"name":"The Rosetrees Trust","award":["A798"],"award-info":[{"award-number":["A798"]}]},{"DOI":"10.13039\/501100004963","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["FP7-CP-FP Epihealth (278418)"],"award-info":[{"award-number":["FP7-CP-FP Epihealth (278418)"]}],"id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004963","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["FP7-PEOPLE-2012-ITN EpiHealthNet (317146)"],"award-info":[{"award-number":["FP7-PEOPLE-2012-ITN EpiHealthNet (317146)"]}],"id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Environment around conception can influence the developmental programme with lasting effects on gestational and postnatal phenotype and with consequences for adult health and disease risk. Peri-conception exposure comprises a crucial part of the \u2018Developmental Origins of Health and Disease\u2019 (DOHaD) concept. In this review, we consider the effects of maternal undernutrition experienced during the peri-conception period in select human models and in a mouse experimental model of protein restriction. Human datasets indicate that macronutrient deprivation around conception affect the epigenome, with enduring effects on cardiometabolic and neurological health. The mouse model, comprising maternal low protein diet exclusively during the peri-conception period, has revealed a stepwise progression in altered developmental programming following induction through maternal metabolite deficiency. This progression includes differential effects in extra-embryonic and embryonic cell lineages and tissues, leading to maladaptation in the growth trajectory and increased chronic disease comorbidities. The timeline embraces an array of mechanisms across nutrient sensing and signalling, cellular, metabolic, epigenetic and physiological processes with a coordinating role for mTORC1 signalling proposed. Early embryos appear active participants in environmental sensing to optimise the developmental programme for survival but with the trade-off of later disease. Similar adverse health outcomes may derive from other peri-conception environmental experiences, including maternal overnutrition, micronutrient availability, pollutant exposure and assisted reproductive treatments (ART) and support the need for preconception health before pregnancy.<\/jats:p>","DOI":"10.3390\/ijerph18179380","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T21:47:38Z","timestamp":1630964858000},"page":"9380","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Environmental Exposures around Conception: Developmental Pathways Leading to Lifetime Disease Risk"],"prefix":"10.3390","volume":"18","author":[{"given":"Tom P.","family":"Fleming","sequence":"first","affiliation":[{"name":"Biological Sciences, Southampton General Hospital, University of Southampton, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congshan","family":"Sun","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Center for Genetic Muscle Disorders, Hugo W. Moser Research Institute at Kennedy Krieger Institute, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Denisenko","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, 850 Republican St., Rm 242, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Caetano","sequence":"additional","affiliation":[{"name":"Biological Sciences, Southampton General Hospital, University of Southampton, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anan","family":"Aljahdali","sequence":"additional","affiliation":[{"name":"Biological Sciences, Southampton General Hospital, University of Southampton, Southampton SO16 6YD, UK"},{"name":"Department of Biological Sciences, Faculty of Science, Alfaisaliah campus, University of Jeddah, Jeddah 23442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna M.","family":"Gould","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences and Psychiatry, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Khurana","sequence":"additional","affiliation":[{"name":"Biological Sciences, Southampton General Hospital, University of Southampton, Southampton SO16 6YD, UK"},{"name":"Institute for Biogenesis Research, Research Corporation of the University of Hawaii, Manoa, Honolulu, HI 96822, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1016\/S0140-6736(18)30312-X","article-title":"Origins of lifetime health around the time of conception: Causes and consequences","volume":"391","author":"Fleming","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"T33","DOI":"10.1530\/JOE-18-0676","article-title":"Periconceptional environment and the developmental origins of disease","volume":"242","author":"Velazquez","year":"2019","journal-title":"J. Endocrinol."},{"key":"ref_3","first-page":"59","article-title":"Dietary regulation of developmental programming in ruminants: Epigenetic modifications in the germline","volume":"67","author":"Sinclair","year":"2010","journal-title":"Soc. Reprod. Fertil. Suppl."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"skaa358","DOI":"10.1093\/jas\/skaa358","article-title":"Maternal periconceptual nutrition, early pregnancy, and developmental outcomes in beef cattle","volume":"98","author":"Caton","year":"2020","journal-title":"J. Anim. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.theriogenology.2016.04.020","article-title":"Epigenetics in preimplantation mammalian development","volume":"86","author":"Canovas","year":"2016","journal-title":"Theriogenology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1093\/humupd\/dmy021","article-title":"Epigenetic regulation in development: Is the mouse a good model for the human?","volume":"24","author":"Hanna","year":"2018","journal-title":"Hum. Reprod. Update"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"10064","DOI":"10.1073\/pnas.1806333115","article-title":"Paternal diet programs offspring health through sperm- and seminal plasma-specific pathways in mice","volume":"115","author":"Watkins","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1113\/JP278270","article-title":"Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice","volume":"598","author":"Morgan","year":"2020","journal-title":"J. Physiol."},{"key":"ref_9","unstructured":"UNICEF(Ed.) (2019). The State of the World\u2019s Children 2019. Children. Food and Nutrition: Growing Well in a Changing World, United Nations Children\u2019s Fund (UNICEF)."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"T135","DOI":"10.1530\/JOE-18-0683","article-title":"Epidemiological evidence for the developmental origins of health and disease: Effects of prenatal undernutrition in humans","volume":"242","author":"Roseboom","year":"2019","journal-title":"J. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.2337\/dc06-0460","article-title":"Impaired insulin secretion after prenatal exposure to the Dutch famine","volume":"29","author":"Painter","year":"2006","journal-title":"Diabetes Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1093\/ajcn\/70.5.811","article-title":"Obesity at the age of 50 y in men and women exposed to famine prenatally","volume":"70","author":"Ravelli","year":"1999","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1093\/ajcn\/72.5.1101","article-title":"Plasma lipid profiles in adults after prenatal exposure to the Dutch famine","volume":"72","author":"Roseboom","year":"2000","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1136\/heart.84.6.595","article-title":"Coronary heart disease after prenatal exposure to the Dutch famine, 1944\u20131945","volume":"84","author":"Roseboom","year":"2000","journal-title":"Heart"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1093\/ajcn\/84.2.322","article-title":"Early onset of coronary artery disease after prenatal exposure to the Dutch famine","volume":"84","author":"Painter","year":"2006","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"179","DOI":"10.3945\/ajcn.111.022038","article-title":"Survival effects of prenatal famine exposure","volume":"95","author":"Veenendaal","year":"2012","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.socscimed.2013.10.027","article-title":"Independent and additive association of prenatal famine exposure and intermediary life conditions with adult mortality between age 18\u201363 years","volume":"119","author":"Ekamper","year":"2014","journal-title":"Soc. Sci. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1176\/ajp.153.12.1637","article-title":"Schizoid personality disorder after prenatal exposure to famine","volume":"153","author":"Hoek","year":"1996","journal-title":"Am. J. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16881","DOI":"10.1073\/pnas.1009459107","article-title":"Prenatal undernutrition and cognitive function in late adulthood","volume":"107","author":"Wouters","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1093\/brain\/aww132","article-title":"Prenatal famine exposure has sex-specific effects on brain size","volume":"139","author":"Caan","year":"2016","journal-title":"Brain J. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.neuroimage.2017.10.047","article-title":"Premature brain aging in humans exposed to maternal nutrient restriction during early gestation","volume":"173","author":"Franke","year":"2018","journal-title":"NeuroImage"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wang, P.X., Wang, J.J., Lei, Y.X., Xiao, L., and Luo, Z.C. (2012). Impact of fetal and infant exposure to the Chinese Great Famine on the risk of hypertension in adulthood. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049720"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1093\/schbul\/sbn168","article-title":"Prenatal malnutrition and adult schizophrenia: Further evidence from the 1959\u20131961 Chinese famine","volume":"35","author":"Xu","year":"2009","journal-title":"Schizophr. Bull."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"17046","DOI":"10.1073\/pnas.0806560105","article-title":"Persistent epigenetic differences associated with prenatal exposure to famine in humans","volume":"105","author":"Heijmans","year":"2008","journal-title":"Proc. Natl Acad Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5592","DOI":"10.1038\/ncomms6592","article-title":"DNA methylation signatures link prenatal famine exposure to growth and metabolism","volume":"5","author":"Tobi","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1093\/ije\/dyv043","article-title":"Early gestation as the critical time-window for changes in the prenatal environment to affect the adult human blood methylome","volume":"44","author":"Tobi","year":"2015","journal-title":"Int. J. Epidemiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"eaao4364","DOI":"10.1126\/sciadv.aao4364","article-title":"DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood","volume":"4","author":"Tobi","year":"2018","journal-title":"Sci. Adv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13148-019-0676-3","article-title":"Early-life exposure to severe famine is associated with higher methylation level in the IGF2 gene and higher total cholesterol in late adulthood: The Genomic Research of the Chinese Famine (GRECF) study","volume":"11","author":"Shen","year":"2019","journal-title":"Clin. Epigenetics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12212","DOI":"10.1038\/s41598-020-69120-w","article-title":"DNA methylation of the INSR gene as a mediator of the association between prenatal exposure to famine and adulthood waist circumference","volume":"10","author":"Wang","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/41245","article-title":"Season of birth predicts mortality in rural Gambia","volume":"388","author":"Moore","year":"1997","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Waterland, R.A., Kellermayer, R., Laritsky, E., Rayco-Solon, P., Harris, R.A., Travisano, M., Zhang, W., Torskaya, M.S., Zhang, J., and Shen, L. (2010). Season of conception in rural gambia affects DNA methylation at putative human metastable epialleles. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1001252"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3746","DOI":"10.1038\/ncomms4746","article-title":"Maternal nutrition at conception modulates DNA methylation of human metastable epialleles","volume":"5","author":"Moore","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s13059-015-0660-y","article-title":"Independent genomewide screens identify the tumor suppressor VTRNA2-1 as a human epiallele responsive to periconceptional environment","volume":"16","author":"Silver","year":"2015","journal-title":"Genome Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"eaat2624","DOI":"10.1126\/sciadv.aat2624","article-title":"Establishment of environmentally sensitive DNA methylation states in the very early human embryo","volume":"4","author":"Kessler","year":"2018","journal-title":"Sci. Adv."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Vaiserman, A. (2020). Season-of-birth phenomenon in health and longevity: Epidemiologic evidence and mechanistic considerations. J. Dev. Orig. Health Dis., 1\u201310.","DOI":"10.1017\/S2040174420001221"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9675","DOI":"10.1038\/s41598-020-66729-9","article-title":"Periconceptional environment predicts leukocyte telomere length in a cross-sectional study of 7\u20139 year old rural Gambian children","volume":"10","author":"Maasen","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1161\/CIRCGENETICS.113.000485","article-title":"Association between shortened leukocyte telomere length and cardiometabolic outcomes: Systematic review and meta-analysis","volume":"8","author":"Ross","year":"2015","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4195","DOI":"10.1242\/dev.127.19.4195","article-title":"Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension","volume":"127","author":"Kwong","year":"2000","journal-title":"Development"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1071\/RD14455","article-title":"Do little embryos make big decisions? How maternal dietary protein restriction can permanently change an embryo","volume":"27","author":"Fleming","year":"2015","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1095\/biolreprod.107.064220","article-title":"Adaptive responses by mouse early embryos to maternal diet protect fetal growth but predispose to adult onset disease","volume":"78","author":"Watkins","year":"2008","journal-title":"Biol. Reprod."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1017\/S0007114509993783","article-title":"Maternal low-protein diet during mouse pre-implantation development induces vascular dysfunction and altered renin-angiotensin-system homeostasis in the offspring","volume":"103","author":"Watkins","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Watkins, A.J., Lucas, E.S., Wilkins, A., Cagampang, F.R., and Fleming, T.P. (2011). Maternal periconceptional and gestational low protein diet affects mouse offspring growth, cardiovascular and adipose phenotype at 1 year of age. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028745"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"E7398","DOI":"10.1073\/pnas.1721876115","article-title":"Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory","volume":"115","author":"Gould","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1017\/S204017442000046X","article-title":"Periconception maternal low-protein diet adversely affects male mouse fetal bone growth and mineral density quality in late gestation","volume":"12","author":"Lanham","year":"2021","journal-title":"J. Dev. Orig. Health Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"321","DOI":"10.22203\/eCM.v022a24","article-title":"Animal models of maternal nutrition and altered offspring bone structure\u2014Bone development across the lifecourse","volume":"22","author":"Lanham","year":"2011","journal-title":"Eur. Cell Mater."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Eckert, J.J., Porter, R., Watkins, A.J., Burt, E., Brooks, S., Leese, H.J., Humpherson, P.G., Cameron, I.T., and Fleming, T.P. (2012). Metabolic induction and early responses of mouse blastocyst developmental programming following maternal low protein diet affecting life-long health. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052791"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12958-019-0458-y","article-title":"Preovulatory exposure to a protein-restricted diet disrupts amino acid kinetics and alters mitochondrial structure and function in the rat oocyte and is partially rescued by folic acid","volume":"17","author":"Schutt","year":"2019","journal-title":"Reprod. Biol. Endocrinol. RBE"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1002\/mrd.22117","article-title":"Cell volume regulation in mammalian oocytes and preimplantation embryos","volume":"79","author":"Baltz","year":"2012","journal-title":"Mol. Reprod. Dev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/978-1-61779-971-6_7","article-title":"Media composition: Amino acids and cellular homeostasis","volume":"912","author":"Houghton","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/S1472-6483(10)60234-9","article-title":"Symposium: Innovative techniques in human embryo viability assessment. Assessing embryo viability by measurement of amino acid turnover","volume":"17","author":"Sturmey","year":"2008","journal-title":"Reprod. Biomed. Online"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1093\/humrep\/deh409","article-title":"Identification of viable embryos in IVF by non-invasive measurement of amino acid turnover","volume":"19","author":"Brison","year":"2004","journal-title":"Hum. Reprod."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1093\/humrep\/dem147","article-title":"Human embryos developing in vitro are susceptible to impaired epithelial junction biogenesis correlating with abnormal metabolic activity","volume":"22","author":"Eckert","year":"2007","journal-title":"Hum. Reprod."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"38078","DOI":"10.1038\/srep38078","article-title":"Uterine glands impact uterine receptivity, luminal fluid homeostasis and blastocyst implantation","volume":"6","author":"Kelleher","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Forde, N., Simintiras, C.A., Sturmey, R., Mamo, S., Kelly, A.K., Spencer, T.E., Bazer, F.W., and Lonergan, P. (2014). Amino acids in the uterine luminal fluid reflects the temporal changes in transporter expression in the endometrium and conceptus during early pregnancy in cattle. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100010"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1007\/s43032-019-00040-5","article-title":"Metabolic Changes of Maternal Uterine Fluid, Uterus, and Plasma during the Peri-implantation Period of Early Pregnancy in Mice","volume":"27","author":"Yang","year":"2020","journal-title":"Reprod. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1079\/BJN2002695","article-title":"Serum concentrations of homocysteine are elevated during early pregnancy in rodent models of fetal programming","volume":"88","author":"Petrie","year":"2002","journal-title":"Br. J. Nutr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12929-020-00679-2","article-title":"Amino acid-dependent control of mTORC1 signaling: A variety of regulatory modes","volume":"27","author":"Takahara","year":"2020","journal-title":"J. Biomed. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1095\/biolreprod.103.018010","article-title":"Amino acid transport regulates blastocyst implantation","volume":"69","author":"Martin","year":"2003","journal-title":"Biol Reprod."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/humupd\/dmi044","article-title":"System B0,+ amino acid transport regulates the penetration stage of blastocyst implantation with possible long-term developmental consequences through adulthood","volume":"12","author":"Tesch","year":"2006","journal-title":"Hum. Reprod. Update"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/bs.ircmb.2015.07.006","article-title":"Ribosomal Protein S6 Phosphorylation: Four Decades of Research","volume":"320","author":"Meyuhas","year":"2015","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/onc.2012.606","article-title":"Ribosomal protein S6 kinase activity controls the ribosome biogenesis transcriptional program","volume":"33","author":"Chauvin","year":"2014","journal-title":"Oncogene"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.bbadis.2017.11.020","article-title":"Insulin and branched-chain amino acid depletion during mouse preimplantation embryo culture programmes body weight gain and raised blood pressure during early postnatal life","volume":"1864","author":"Velazquez","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1242\/dev.103952","article-title":"Mouse early extra-embryonic lineages activate compensatory endocytosis in response to poor maternal nutrition","volume":"141","author":"Sun","year":"2014","journal-title":"Development"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3389\/fcell.2019.00276","article-title":"p38-Mitogen Activated Kinases Mediate a Developmental Regulatory Response to Amino Acid Depletion and Associated Oxidative Stress in Mouse Blastocyst Embryos","volume":"7","author":"Bora","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Caetano, L., Eckert, J., Johnston, D., Chatelet, D., Tumbarello, D., Smyth, N., Ingamells, S., Price, A., and Fleming, T. (2021). Blastocyst trophectoderm endocytic activation, a marker of adverse developmental programming. Reproduction.","DOI":"10.1530\/REP-21-0234"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1079\/PNS2001137","article-title":"Manipulating the sulfur amino acid content of the early diet and its implications for long-term health","volume":"61","author":"Rees","year":"2002","journal-title":"Proc. Nutr. Soc."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1093\/humupd\/dmt041","article-title":"The periconceptional period, reproduction and long-term health of offspring: The importance of one-carbon metabolism","volume":"19","author":"Twigt","year":"2013","journal-title":"Hum. Reprod. Update"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"300","DOI":"10.3389\/fcell.2019.00300","article-title":"One-Carbon Metabolism Regulates Embryonic Stem Cell Fate Through Epigenetic DNA and Histone Modifications: Implications for Transgenerational Metabolic Disorders in Adults","volume":"7","author":"Ryznar","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Van Winkle, L.J., Galat, V., and Iannaccone, P.M. (2020). Lysine Deprivation during Maternal Consumption of Low-Protein Diets Could Adversely Affect Early Embryo Development and Health in Adulthood. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17155462"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1095\/biolreprod.108.072595","article-title":"Metabolic and mitochondrial dysfunction in early mouse embryos following maternal dietary protein intervention","volume":"80","author":"Mitchell","year":"2009","journal-title":"Biol. Reprod."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Chiaratti, M.R., Malik, S., Diot, A., Rapa, E., Macleod, L., Morten, K., Vatish, M., Boyd, R., and Poulton, J. (2015). Is Placental Mitochondrial Function a Regulator that Matches Fetal and Placental Growth to Maternal Nutrient Intake in the Mouse?. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130631"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1016\/j.bbamcr.2008.08.011","article-title":"ERK and p38 pathways regulate amino acid signalling","volume":"1783","author":"Tato","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"14951","DOI":"10.1002\/jcp.28334","article-title":"RAS\/MAPK signaling functions in oxidative stress, DNA damage response and cancer progression","volume":"234","author":"Rezatabar","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_74","first-page":"1997","article-title":"ERK\/MAPK signalling pathway and tumorigenesis","volume":"19","author":"Guo","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.devcel.2013.05.004","article-title":"Oct4 cell-autonomously promotes primitive endoderm development in the mouse blastocyst","volume":"25","author":"Frum","year":"2013","journal-title":"Dev. Cell"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ydbio.2018.02.007","article-title":"GATA6 phosphorylation by Erk1\/2 propels exit from pluripotency and commitment to primitive endoderm","volume":"436","author":"Meng","year":"2018","journal-title":"Dev. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"160190","DOI":"10.1098\/rsob.160190","article-title":"p38 (Mapk14\/11) occupies a regulatory node governing entry into primitive endoderm differentiation during preimplantation mouse embryo development","volume":"6","author":"Thamodaran","year":"2016","journal-title":"Open Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"20130538","DOI":"10.1098\/rstb.2013.0538","article-title":"Developmental plasticity, cell fate specification and morphogenesis in the early mouse embryo","volume":"369","author":"Bedzhov","year":"2014","journal-title":"Philos. Trans. R Soc. Lond. B Biol. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1095\/biolreprod.110.085209","article-title":"Establishing three blastocyst lineages\u2014Then what?","volume":"84","author":"Gasperowicz","year":"2011","journal-title":"Biol. Reprod."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0890-6238(97)00147-0","article-title":"Quantitative studies on the mechanisms of amino acid supply to rat embryos during organogenesis","volume":"12","author":"Beckman","year":"1998","journal-title":"Reprod. Toxicol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.ydbio.2011.10.021","article-title":"Leucine and arginine regulate trophoblast motility through mTOR-dependent and independent pathways in the preimplantation mouse embryo","volume":"361","author":"Martin","year":"2012","journal-title":"Dev. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1095\/biolreprod.104.036913","article-title":"Expression and role of cubilin in the internalization of nutrients during the peri-implantation development of the rodent embryo","volume":"72","author":"Assemat","year":"2005","journal-title":"Biol. Reprod."},{"key":"ref_83","first-page":"175","article-title":"Maturation and polarization of the endocytotic system in outside blastomeres during mouse preimplantation development","volume":"89","author":"Fleming","year":"1985","journal-title":"J. Embryol. Exp. Morphol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1210\/er.2018-00281","article-title":"Uterine Glands: Developmental Biology and Functional Roles in Pregnancy","volume":"40","author":"Kelleher","year":"2019","journal-title":"Endocr. Rev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e98804","DOI":"10.15252\/embj.201798804","article-title":"The complex relationship between TFEB transcription factor phosphorylation and subcellular localization","volume":"37","author":"Puertollano","year":"2018","journal-title":"EMBO J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"jcs236661","DOI":"10.1242\/jcs.236661","article-title":"The small GTPase Rab32 resides on lysosomes to regulate mTORC1 signaling","volume":"133","author":"Chen","year":"2020","journal-title":"J. Cell Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1530\/REP-14-0667","article-title":"Maternal nutrition modifies trophoblast giant cell phenotype and fetal growth in mice","volume":"149","author":"Watkins","year":"2015","journal-title":"Reproduction"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1113\/jphysiol.2009.181214","article-title":"Adaptations in placental phenotype support fetal growth during undernutrition of pregnant mice","volume":"588","author":"Coan","year":"2010","journal-title":"J. Physiol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Sun, C., Denisenko, O., Sheth, B., Cox, A., Lucas, E.S., Smyth, N.R., and Fleming, T.P. (2015). Epigenetic regulation of histone modifications and Gata6 gene expression induced by maternal diet in mouse embryoid bodies in a model of developmental programming. BMC Dev. Biol., 15.","DOI":"10.1186\/s12861-015-0053-1"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Law, P.P., and Holland, M.L. (2018). Deciphering the Role of the Non-Coding Genome in Regulating Gene-Diet Interactions. Nutrients, 10.","DOI":"10.3390\/nu10121831"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Gensous, N., Ravaioli, F., Pirazzini, C., Gramignoli, R., Ellis, E., Storci, G., Capri, M., Strom, S., Laconi, E., and Franceschi, C. (2020). Aging and Caloric Restriction Modulate the DNA Methylation Profile of the Ribosomal RNA Locus in Human and Rat Liver. Nutrients, 12.","DOI":"10.3390\/nu12020277"},{"key":"ref_92","unstructured":"Uchiumi, F. (2018). Control of Ribosomal RNA Transcription by Nutrients. Gene Expression and Regulation in Mammalian Cells\u2014Transcription Toward the Establishment of Novel Therapeutics, BoD."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1146\/annurev.cellbio.24.110707.175259","article-title":"The epigenetics of rRNA genes: From molecular to chromosome biology","volume":"24","author":"McStay","year":"2008","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.bbagrm.2016.04.001","article-title":"Regulation of ribosomal RNA expression across the lifespan is fine-tuned by maternal diet before implantation","volume":"1859","author":"Denisenko","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e20832","DOI":"10.7554\/eLife.20832","article-title":"The dynamic assembly of distinct RNA polymerase I complexes modulates rDNA transcription","volume":"6","author":"Torreira","year":"2017","journal-title":"Elife"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1080\/21541264.2017.1416267","article-title":"RNA polymerase I activation and hibernation: Unique mechanisms for unique genes","volume":"9","year":"2018","journal-title":"Transcription"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1126\/science.aaf7040","article-title":"Early-life nutrition modulates the epigenetic state of specific rDNA genetic variants in mice","volume":"353","author":"Holland","year":"2016","journal-title":"Science"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/bmb\/60.1.5","article-title":"The thrifty phenotype hypothesis","volume":"60","author":"Hales","year":"2001","journal-title":"Br. Med. Bull."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1007\/s00125-012-2589-y","article-title":"The thrifty phenotype hypothesis revisited","volume":"55","author":"Vaag","year":"2012","journal-title":"Diabetologia"},{"key":"ref_100","first-page":"353","article-title":"Diabetes mellitus: A \u201cthrifty\u201d genotype rendered detrimental by \u201cprogress\u201d?","volume":"14","author":"Neel","year":"1962","journal-title":"Am. J. Hum. Genet."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1111\/ahg.12132","article-title":"Pacific Populations, Metabolic Disease and \u2018Just-So Stories\u2019: A Critique of the \u2018Thrifty Genotype\u2019 Hypothesis in Oceania","volume":"79","author":"Gosling","year":"2015","journal-title":"Ann. Hum. Genet."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1101\/gad.285504","article-title":"mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability","volume":"18","author":"Mayer","year":"2004","journal-title":"Genes Dev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3389\/fnut.2020.00081","article-title":"PTEN: A Thrifty Gene That Causes Disease in Times of Plenty?","volume":"7","author":"Venniyoor","year":"2020","journal-title":"Front. Nutr."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1093\/biolre\/ioaa070","article-title":"Is there a definite relationship between placental mTOR signaling and fetal growth?","volume":"103","author":"Dong","year":"2020","journal-title":"Biol. Reprod."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"583801","DOI":"10.3389\/fcell.2020.583801","article-title":"mTORC1 Transcriptional Regulation of Ribosome Subunits, Protein Synthesis, and Molecular Transport in Primary Human Trophoblast Cells","volume":"8","author":"Rosario","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4874","DOI":"10.1016\/j.jmb.2018.10.008","article-title":"Transcriptional and Epigenetic Regulation by the Mechanistic Target of Rapamycin Complex 1 Pathway","volume":"430","author":"Laribee","year":"2018","journal-title":"J. Mol. Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1055\/s-0029-1237424","article-title":"Developmental origins of health and disease: Brief history of the approach and current focus on epigenetic mechanisms","volume":"27","author":"Wadhwa","year":"2009","journal-title":"Semin. Reprod. Med."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"G\u00fcrke, J., Hirche, F., Thieme, R., Haucke, E., Schindler, M., Stangl, G.I., Fischer, B., and Navarrete Santos, A. (2015). Maternal Diabetes Leads to Adaptation in Embryonic Amino Acid Metabolism during Early Pregnancy. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127465"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1093\/humrep\/dev008","article-title":"Amino acid composition of human uterine fluid: Association with age, lifestyle and gynaecological pathology","volume":"30","author":"Kermack","year":"2015","journal-title":"Hum. Reprod."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.fertnstert.2019.09.041","article-title":"Effect of a 6-week \"Mediterranean\" dietary intervention on in vitro human embryo development: The Preconception Dietary Supplements in Assisted Reproduction double-blinded randomized controlled trial","volume":"113","author":"Kermack","year":"2020","journal-title":"Fertil. Steril."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3389\/fcell.2018.00107","article-title":"Periconceptional Maternal Mediterranean Diet Is Associated With Favorable Offspring Behaviors and Altered CpG Methylation of Imprinted Genes","volume":"6","author":"House","year":"2018","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.fertnstert.2017.01.017","article-title":"Obesity and female infertility: Potential mediators of obesity\u2019s impact","volume":"107","author":"Broughton","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1210\/jc.2008-2648","article-title":"Obese women exhibit differences in ovarian metabolites, hormones, and gene expression compared with moderate-weight women","volume":"94","author":"Robker","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Igosheva, N., Abramov, A.Y., Poston, L., Eckert, J.J., Fleming, T.P., Duchen, M.R., and McConnell, J. (2010). Maternal Diet-Induced Obesity Alters Mitochondrial Activity and Redox Status in Mouse Oocytes and Zygotes. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010074"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1093\/humrep\/deu276","article-title":"Human embryos from overweight and obese women display phenotypic and metabolic abnormalities","volume":"30","author":"Leary","year":"2015","journal-title":"Hum. Reprod."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1042\/CS20190266","article-title":"Placental function in maternal obesity","volume":"134","author":"Kelly","year":"2020","journal-title":"Clin. Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"R69","DOI":"10.1530\/REP-18-0130","article-title":"Effects of micronutrients on placental function: Evidence from clinical studies to animal models","volume":"156","author":"Baker","year":"2018","journal-title":"Reproduction"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Schr\u00f6der-Heurich, B., Springer, C.J.P., and von Versen-H\u00f6ynck, F. (2020). Vitamin D Effects on the Immune System from Periconception through Pregnancy. Nutrients, 12.","DOI":"10.3390\/nu12051432"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"19351","DOI":"10.1073\/pnas.0707258104","article-title":"DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status","volume":"104","author":"Sinclair","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3945\/jn.109.119453","article-title":"A methyl-deficient diet fed to rat dams during the peri-conception period programs glucose homeostasis in adult male but not female offspring","volume":"141","author":"Maloney","year":"2011","journal-title":"J. Nutr."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1146\/annurev-animal-020518-115206","article-title":"One-Carbon Metabolism: Linking Nutritional Biochemistry to Epigenetic Programming of Long-Term Development","volume":"7","author":"Clare","year":"2019","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1017\/S2040174419000217","article-title":"Maternal folic acid depletion during early pregnancy increases sensitivity to squamous tumor formation in the offspring in mice","volume":"10","author":"Morioka","year":"2019","journal-title":"J. Dev. Orig. Health Dis."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/mrd.23462","article-title":"High maternal folic acid intake around conception alters mouse blastocyst lineage allocation and expression of key developmental regulatory genes","volume":"88","author":"Penailillo","year":"2021","journal-title":"Mol. Reprod. Dev."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Vecoli, C., Pulignani, S., and Andreassi, M.G. (2016). Genetic and Epigenetic Mechanisms Linking Air Pollution and Congenital Heart Disease. J. Cardiovasc. Dev. Dis., 3.","DOI":"10.3390\/jcdd3040032"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"110694","DOI":"10.1016\/j.envres.2020.110694","article-title":"Endocrine disrupting chemicals: Impacts on human fertility and fecundity during the peri-conception period","volume":"194","author":"Green","year":"2021","journal-title":"Environ. Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1146\/annurev-pharmtox-010818-021304","article-title":"Environmental Obesogens: Mechanisms and Controversies","volume":"59","author":"Heindel","year":"2019","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"513","DOI":"10.3389\/fendo.2018.00513","article-title":"Developmental Exposure to Endocrine Disrupting Chemicals and Type 1 Diabetes Mellitus","volume":"9","author":"Howard","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1093\/humrep\/dew156","article-title":"Influence of embryo culture medium (G5 and HTF) on pregnancy and perinatal outcome after IVF: A multicenter RCT","volume":"31","author":"Kleijkers","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1210\/jc.2007-2432","article-title":"Cardiometabolic differences in children born after in vitro fertilization: Follow-up study","volume":"93","author":"Ceelen","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Gkourogianni, A., Kosteria, I., Telonis, A.G., Margeli, A., Mantzou, E., Konsta, M., Loutradis, D., Mastorakos, G., Papassotiriou, I., and Klapa, M.I. (2014). Plasma metabolomic profiling suggests early indications for predisposition to latent insulin resistance in children conceived by ICSI. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094001"},{"key":"ref_131","first-page":"291","article-title":"Postnatal persistence of fetal cardiovascular remodelling associated with assisted reproductive technologies: A cohort study","volume":"126","author":"Serafini","year":"2018","journal-title":"BJOG"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"103076","DOI":"10.1016\/j.ebiom.2020.103076","article-title":"Integrated multi-omics reveal epigenomic disturbance of assisted reproductive technologies in human offspring","volume":"61","author":"Chen","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"3922","DOI":"10.1038\/s41467-019-11929-9","article-title":"Assisted reproductive technologies are associated with limited epigenetic variation at birth that largely resolves by adulthood","volume":"10","author":"Novakovic","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"5449","DOI":"10.1073\/pnas.0610317104","article-title":"Mouse embryo culture induces changes in postnatal phenotype including raised systolic blood pressure","volume":"104","author":"Watkins","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"5052","DOI":"10.1172\/JCI68943","article-title":"Mice generated by in vitro fertilization exhibit vascular dysfunction and shortened life span","volume":"123","author":"Rexhaj","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1093\/humrep\/dex361","article-title":"Birthweight of singletons born after cleavage-stage or blastocyst transfer in fresh and warming cycles","volume":"33","author":"Tournaye","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.rbmo.2018.12.031","article-title":"Comparison of perinatal outcomes following blastocyst and cleavage-stage embryo transfer: Analysis of 10 years\u2019 data from a single centre","volume":"38","author":"Shi","year":"2019","journal-title":"Reprod. Biomed. Online"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1093\/humrep\/deaa205","article-title":"The duration of embryo culture after mouse IVF differentially affects cardiovascular and metabolic health in male offspring","volume":"35","author":"Aljahdali","year":"2020","journal-title":"Hum. Reprod."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Hu, R., Li, Y., Yang, Y., and Liu, M. (2021). Mass spectrometry-based strategies for single-cell metabolomics. Mass Spectrom. Rev.","DOI":"10.1002\/mas.21704"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Yan, Z., An, J., Peng, Y., Kong, S., Liu, Q., Yang, M., He, Q., Song, S., Chen, Y., and Chen, W. (2021). DevOmics: An integrated multi-omics database of human and mouse early embryo. Brief. Bioinform., bbab208.","DOI":"10.1093\/bib\/bbab208"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Rabaglino, M.B., O\u2019Doherty, A., Bojsen-M\u00f8ller Secher, J., Lonergan, P., Hyttel, P., Fair, T., and Kadarmideen, H.N. (2021). Application of multi-omics data integration and machine learning approaches to identify epigenetic and transcriptomic differences between in vitro and in vivo produced bovine embryos. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0252096"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1093\/humrep\/dev179","article-title":"Differences in gene expression profiles between human preimplantation embryos cultured in two different IVF culture media","volume":"30","author":"Kleijkers","year":"2015","journal-title":"Hum. Reprod."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1071\/RD14359","article-title":"Applying metabolomic analyses to the practice of embryology: Physiology, development and assisted reproductive technology","volume":"27","author":"Krisher","year":"2015","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1080\/19396368.2019.1625085","article-title":"Can trophectoderm RNA analysis predict human blastocyst competency?","volume":"65","author":"Ntostis","year":"2019","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1016\/j.stem.2021.04.027","article-title":"Integrated pseudotime analysis of human pre-implantation embryo single-cell transcriptomes reveals the dynamics of lineage specification","volume":"28","author":"Meistermann","year":"2021","journal-title":"Cell Stem Cell"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Khurana, P., Smyth, N.R., Sheth, B., Velazquez, M.A., Eckert, J.J., and Fleming, T.P. (2021). Advanced maternal age perturbs mouse embryo development and alters the phenotype of derived embryonic stem cells. J. Dev. Orig. Health Dis., 1\u201311.","DOI":"10.1017\/S2040174421000325"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Simbulan, R.K., Di Santo, M., Liu, X., Lin, W., Donjacour, A., Maltepe, E., Shenoy, A., Borini, A., and Rinaudo, P. (2015). Embryonic stem cells derived from in vivo or in vitro-generated murine blastocysts display similar transcriptome and differentiation potential. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0117422"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1016\/S0140-6736(18)30311-8","article-title":"Before the beginning: Nutrition and lifestyle in the preconception period and its importance for future health","volume":"391","author":"Stephenson","year":"2018","journal-title":"Lancet"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"20180123","DOI":"10.1098\/rstb.2018.0123","article-title":"Metabolic programming in early life in humans","volume":"374","author":"Fall","year":"2019","journal-title":"Philos. Trans. R Soc. Lond. B Biol. Sci."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1093\/emph\/eoz037","article-title":"The Maternal Nutritional Buffering Model: An evolutionary framework for pregnancy nutritional intervention","volume":"2020","author":"Thayer","year":"2020","journal-title":"Evol. Med. Public Health"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/ijgo.13331","article-title":"Prevention of noncommunicable diseases by interventions in the preconception period: A FIGO position paper for action by healthcare practitioners","volume":"151","author":"Jacob","year":"2020","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.jpeds.2020.09.032","article-title":"Growth from Birth Through Six Months for Infants of Mothers in the \u201cWomen First\u201d Preconception Maternal Nutrition Trial","volume":"229","author":"Krebs","year":"2021","journal-title":"J. Pediatrics"},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Salavati, N., Bakker, M.K., Lewis, F., Vinke, P.C., Mubarik, F., Erwich, J.H.M., and van der Beek, E.M. (2020). Associations between preconception macronutrient intake and birth weight across strata of maternal BMI. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0243200"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1093\/ajcn\/nqaa193","article-title":"Effect of maternal preconceptional and pregnancy micronutrient interventions on children\u2019s DNA methylation: Findings from the EMPHASIS study","volume":"112","author":"Saffari","year":"2020","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1016\/S0140-6736(18)30313-1","article-title":"Intervention strategies to improve nutrition and health behaviours before conception","volume":"391","author":"Barker","year":"2018","journal-title":"Lancet"}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/17\/9380\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:56:59Z","timestamp":1760165819000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/17\/9380"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,6]]},"references-count":155,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijerph18179380"],"URL":"https:\/\/doi.org\/10.3390\/ijerph18179380","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,6]]}}}