Cited by 328Genetic Syndromes and ImprintingBirth, Development, and HealthPregnancy and preeclampsia studies

The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.

Adaptation of nutrient supply to fetal demand in the mouse involves interaction between the Igf2 gene and placental transporter systems

Open access

Constância, Miguel, Angiolini, Emily, Sandovici, Ionel, Smith, Paul, Smith, Rachel, Kelsey, Gavin, Dean, Wendy, Ferguson-Smith, Anne, Sibley, Colin P., Reik, Wolf, Fowden, Abigail·2005·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0504468103PMC PMC1316882

Open this paper in CoChat — free account

Abstract

The mammalian fetus is unique in its dependence during gestation on the supply of maternal nutrients through the placenta. Maternal supply and fetal demand for nutrients need to be fine tuned for healthy growth and development of the fetus along its genetic trajectory. An altered balance between supply and demand can lead to deviations from this trajectory with long-term consequences for health. We have previously shown that in a knockout lacking the imprinted placental-specific Igf2 transcript (P0), growth of the placenta is compromised from early gestation but fetal growth is normal until late gestation, suggesting functional adaptation of the placenta to meet the fetal demands. Here, we show that placental transport of glucose and amino acids are increased in the Igf2 P0 +/- null and that this up-regulation of transport occurs, at least in part, through increased expression of the transporter genes Slc2a3 and Slc38a4 , the imprinted member of the System A amino acid transporter gene family. Decreasing fetal demand genetically by removal of fetal Igf2 abolished up-regulation of both transport systems and reduced placental System A amino acid transport activity and expression of Slc38a2 in late gestation. Our results provide direct evidence that the placenta can respond to fetal demand signals through regulation of expression of specific placental transport systems. Thus, crosstalk between an imprinted growth demand gene ( Igf2 ) and placental supply transporter genes ( Slc38a4 , Slc38a2 , and Slc2a3 ) may be a component of the genetic control of nutrient supply and demand during mammalian development.

Integrity signals

Registry

Crossref · 10.1073/pnas.0504468103

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Genomic imprinting: parental influence on the genome
Reik, W., & Walter, J. (2001) · Nature Reviews Genetics · doi:10.1038/35047554 · Cited by 2,288
Self-citation
Genomic imprinting in mammalian development: a parental tug-of-war
Moore, T. (1991) · Trends in Genetics · doi:10.1016/0168-9525(91)90230-n · Cited by 1,281
Placental-specific IGF-II is a major modulator of placental and fetal growth
Constância, M., Hemberger, M., Hughes, J., Dean, W., Ferguson-Smith, A., Fundele, R., Stewart, F., Kelsey, G., Fowden, A., Sibley, C., et al. (2002) · Nature · doi:10.1038/nature00819 · Cited by 1,054
Self-citation
Sodium-coupled neutral amino acid (System N/A) transporters of the SLC38 gene family
Mackenzie, B., & Erickson, J. D. (2004) · Pfl�gers Archiv European Journal of Physiology · doi:10.1007/s00424-003-1117-9 · Cited by 515
The SLC2 family of facilitated hexose and polyol transporters
Uldry, M., & Thorens, B. (2004) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-003-1085-0 · Cited by 494
What good is genomic imprinting: the function of parent-specific gene expression
Wilkins, J. F., & Haig, D. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1062 · Cited by 490
Endocrine mechanisms of intrauterine programming.
Fowden, A., & Forhead, A. (2004) · Reproduction · doi:10.1530/rep.1.00033 · Cited by 470
Self-citation
Regulation of supply and demand for maternal nutrients in mammals by imprinted genes
Reik, W., Constância, M., Fowden, A. L., Anderson, N. F., Dean, W., Ferguson‐Smith, A. C., Tycko, B., & Sibley, C. P. (2003) · The Journal of Physiology · doi:10.1111/j.1469-7793.2003.00035.x · Cited by 409
Self-citation
Imprinting and the Epigenetic Asymmetry Between Parental Genomes
Ferguson‐Smith, A. C., & Surani, M. A. (2001) · Science · doi:10.1126/science.1064020 · Cited by 405
Self-citation
Genetics of mouse growth
Efstratiadis, A. (1998) · The International Journal of Developmental Biology · doi:10.1387/ijdb.9853827 · Cited by 357

Show all 34 references

Research works printed but not linked: 5

10.1016/0168-9525(91)90040-W · DOI · Paper page
Godfrey, K. M., Matthews, N., Glazier, J., Jackson, A., Wilman, C. & Sibley, C. P. (1998) J. Clin. Endocrinol. Metab. 83, 3320-3326.9745448
Kniss, D. A., Shubert, P. J., Zimmerman, P. D., Landon, M. B. & Gabbe, S. G. (1994) J. Reprod. Med. 39, 249-256.8040840
Robinson, J. S., Kingston, E. J., Jones, C. T. & Thorburn, G. D. (1979) J. Dev. Physiol. 1, 379-398.45373
Efstratiadis, A. (1998) Int. J. Dev. Biol. 42, 955-976.9853827

Sorted by citations

Items 201–300 of 328

Association of SLC38A4 and system A with abnormal fetal birth weight.
Li, Z., Lai, G., Deng, L.-J., Han, Y., Zheng, D., & Song, W.-W. (2012) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2011.392 · Cited by 18
“In addition, Constancia et al found that enhanced system A activity was partly due to up-regulation in the expression of SNAT4 (26), indicating that SNAT4 plays a crucial role in determining the strength of system A activity.”
Background
Glucose transporter isoform-3-null heterozygous mutation causes sexually dimorphic adiposity with insulin resistance
Ganguly, A., & Devaskar, S. U. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90251.2008 · Cited by 18
“This isoform plays a critical role in mediating transplacental glucose transport that is essential for fueling fetal growth and energy metabolism (3, 12, 14).”
Background
System A activity and vascular function in the placental-specific Igf2 knockout mouse
Kusinski, L. C., Dilworth, M. R., Baker, P. N., Sibley, C. P., Wareing, M., & Glazier, J. D. (2011) · Placenta · doi:10.1016/j.placenta.2011.07.086 · Cited by 16
“[5,9], showing unidirectional maternofetal transfer of 14C-MeAIB per g placenta was significantly stimulated in P0 mutants at this gestational age.”
BackgroundMethodResultInfluentialSelf-citation
Fetal Requirements and Placental Transfer of Nitrogenous Compounds
Brown, L. D., Regnault, T. R. H., & Hay, W. W. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-35214-7.00045-7 · Cited by 16
Parental obesity-induced changes in developmental programming
Cechinel, L. R., Batabyal, R., Freishtat, R. J., & Zohn, I. E. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.918080 · Cited by 15
Absence of paternal accessory sex gland secretions disturbs epigenetic reprogramming and expression of Igf2 and Dlk1 in golden hamster embryos
Poon, H. K., Lee, K. K., Wong, C. L., O, W. S., & Chow, P. H. (2009) · Theriogenology · doi:10.1016/j.theriogenology.2008.12.016 · Cited by 15
“Furthermore, Igf2 is an important embryonic growth regulator [20–22], whereas Dlk1 encodes a transmembrane protein and its secreted isoforms contain epidermal growth factor repeat motifs closely related to those present in the Delta/Notch/Serrate family of signaling molecules, known to be important in growth and diffe…”
Background
Sodium‐coupled neutral amino acid transporter 4 functions as a regulator of protein synthesis during liver development
Kondou, H., Kawai, M., Tachikawa, K., Kimoto, A., Yamagata, M., Koinuma, T., Yamazaki, M., Nakayama, M., Mushiake, S., Ozono, K., et al. (2013) · Hepatology Research · doi:10.1111/hepr.12069 · Cited by 15
Adaptations in Maternofetal Calcium Transport in Relation to Placental Size and Fetal Sex in Mice
Hayward, C. E., Renshall, L. J., Sibley, C. P., Greenwood, S. L., & Dilworth, M. R. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.01050 · Cited by 15
“In a well characterized mouse model of late onset FGR, the placental-specific insulin-like growth factor 2 knock out (P0) mouse (Constância et al., 2005), there is a reduction in placental weight from E14 which precedes the reduction in fetal weight (E19).”
BackgroundResultSelf-citation
Development of the Human Placental Villus
Aplin, J., Lewis, R. M., & Jones, C. J. P. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.99857-x · Cited by 15
Evidence of adaptation of maternofetal transport of glutamine relative to placental size in normal mice, and in those with fetal growth restriction
McIntyre, K. R., Hayward, C. E., Sibley, C. P., Greenwood, S. L., & Dilworth, M. R. (2019) · The Journal of Physiology · doi:10.1113/jp278226 · Cited by 14
“Genotype (P0 or WTL) was determined for all fetuses from P0 dams according to a previously published genotyping protocol (Constância et al. 2005; Dilworth et al. 2010).”
InfluentialSelf-citation
Placental effects on the maternal brain revealed by disrupted placental gene expression in mouse hybrids
Arévalo, L., & Polly Campbell, A. (2020) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2019.2563 · Cited by 13
Nutritional control of developmental processes
Ferenc, J., & Ikmi, A. (2023) · Development · doi:10.1242/dev.200623 · Cited by 13
Placental alterations in structure and function in intra‐uterine growth‐retarded horses
Robles, M., Peugnet, P., Valentino, S., Dubois, C., Dahirel, M., Aubrière, M.-C., Reigner, F., Serteyn, D. A., Wimel, L., Couturier‐Tarrade, A., et al. (2017) · Equine Veterinary Journal · doi:10.1111/evj.12761 · Cited by 13
“in mice elegantly showed that the placenta will respond to fetal demand and adjust nutrient transfer [40].”
Background
Maternal diet modulates placental nutrient transporter gene expression in a mouse model of diabetic pregnancy
Kappen, C., Krüger, C., Jones, S., Herion, N. J., & Salbaum, J. M. (2019) · PLoS ONE · doi:10.1371/journal.pone.0224754 · Cited by 13
“It is intriguing that breeder diet appears to have a stronger effect on this switch than chow diet, particularly in light of the finding that placental Slc2a3/Glut3 expression is sensitive to Igf2 levels [41].”
Background
Dexamethasone treatment of pregnant F0 mice leads to parent of origin-specific changes in placental function of the F2 generation
Vaughan, O. R., Phillips, H. M., Everden, A. J., Sferruzzi-Perri, A. N., & Fowden, A. L. (2015) · Reproduction Fertility and Development · doi:10.1071/rd14285 · Cited by 13
“Species differences in the effects of F0 manipulations on F2 placental Slc38a4 abundance may reflect yet unidentified morphological changes in the placenta or promoter-specific regulation of the various Slc38a4 transcripts in the present and previous studies (Constância et al. 2005).”
BackgroundSelf-citation
Placental Transfer in Health and Disease
Wright, C., & Sibley, C. P. (2011) · doi:10.1002/9781444393927.ch9 · Cited by 13
Self-citation
Behavioural effects of imprinted genes
Davies, J. R., Dent, C. L., McNamara, G. I., & Isles, A. R. (2014) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2014.07.008 · Cited by 13
“Here too, an imbalance in Igf2 signalling between mother and foetus can be brought about by a placenta-specific deletion of Igf2 expression (Igf2-P0) [29].”
Background
Glucocorticoids and placental programming
Vaughan, O. R., Forhead, A. J., & Fowden, A. L. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511933806.015 · Cited by 12
Self-citation
Endocrinology of Fetal Development
Dattani, M., & Gevers, E. F. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-29738-7.00022-8 · Cited by 13
Growth Factor Regulation of Fetal Growth
Hawkes, C. P., & Katz, L. E. L. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-35214-7.00143-8 · Cited by 12
Extracellular vesicle-mediated targeting strategies for long-term health benefits in gestational diabetes
Nair, S., Ormazábal, V., Carrión, F., Handberg, A., McIntyre, D. H., & Salomón, C. (2023) · Clinical Science · doi:10.1042/cs20220150 · Cited by 13
Distinct promoter methylation and isoform-specific expression of RASFF1A in placental biopsies from complicated pregnancies
Iglesias‐Platas, I., Trujillo, A. M., Court, F., & Monk, D. (2015) · Placenta · doi:10.1016/j.placenta.2015.01.011 · Cited by 11
Assessment of Placental Transport Function in Studies of Disease Programming
Sferruzzi-Perri, A. N. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7614-0_14 · Cited by 10
Functional Expression Study ofIgf2Antisense Transcript in Mouse
Duart-Garcia, C., & Braunschweig, M. (2014) · International Journal of Genomics · doi:10.1155/2014/390296 · Cited by 11
Fetal and Neonatal Endocrinology
Gevers, E. F., Fisher, D. A., & Dattani, M. (2015) · Elsevier eBooks · doi:10.1016/b978-0-323-18907-1.00145-1 · Cited by 11
Deletion of the Imprinted Phlda2 Gene Increases Placental Passive Permeability in the Mouse
Angiolini, E., Sandovici, I., Coan, P. M., Burton, G. J., Sibley, C. P., Fowden, A. L., & Constância, M. (2021) · Genes · doi:10.3390/genes12050639 · Cited by 11
“Igf2 ↓ ↓ (inulin) ↓ No ∆ ↓ ↓ Increases TDC by reducing interhemal membrane thickness and increasing surface area [24,45]”
BackgroundInfluentialSelf-citation
Role and mechanism of insulin‐like growth factor 2 on the proliferation of human trophoblasts in vitro
Chen, H., Li, Y., Shi, J., & Song, W. (2015) · Journal of obstetrics and gynaecology research · doi:10.1111/jog.12853 · Cited by 10
“years has also suggested that IGF2 contributes to the regulation of placentation and prenatal and postnatal growth.(8,9,27) Previous results have shown that the levels”
BackgroundResult
Multigenerational analysis of sex-specific phenotypic differences at midgestation caused by abnormal folate metabolism
Padmanabhan, N., Rakoczy, J., Kondratowicz, M., Menelaou, K., Blake, G. E. T., & Watson, E. D. (2017) · Current Zoology · doi:10.1093/eep/dvx014 · Cited by 11
Transcriptomic analysis reveals the effects of maternal selenium deficiency on placental transport, hormone synthesis, and immune response in mice
Cheng, W., Zhang, L., Sa, P., Luo, J., & Li, M. (2022) · Metallomics · doi:10.1093/mtomcs/mfac062 · Cited by 9
Protective and sex‐specific effects of moderate dose folic acid supplementation on the placenta following assisted reproduction in mice
Ihirwe, R. G., Martel, J., Rahimi, S., & Trasler, J. M. (2022) · The FASEB Journal · doi:10.1096/fj.202201428r · Cited by 9
Sex-Selective Increase of IGF-2 Expression in the Hypoxic Guinea Pig Placenta of Growth-Restricted Fetuses
Elsamadicy, E. A., & Thompson, L. (2022) · Reproductive Sciences · doi:10.1007/s43032-022-00979-y · Cited by 6
“Both complete deletion of the Igf2 gene and deletion of the placenta-specific transcript of Igf2 gene (Igf2P0) in the mouse result in decreased placental and fetal weights [35, 36].”
Background
Cytoplasmatic inheritance, epigenetics and reprogramming DNA as tools in animal breeding
Meirelles, F. V., Bressan, F. F., Smith, L. C., Perecin, F., Chiaratti, M. R., & Ferraz, J. B. S. (2014) · Livestock Science · doi:10.1016/j.livsci.2014.05.024 · Cited by 9
Placenta-Derived Exosomes and Gestational Diabetes Mellitus
Liu, X., & Qiu, H. (2022) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s363226 · Cited by 8
Maternal and Intrauterine Influences on Feto-Placental Growth Are Accompanied by Sexually Dimorphic Changes in Placental Mitochondrial Respiration, and Metabolic Signalling Pathways
Salazar‐Petres, E., Pereira‐Carvalho, D., López‐Tello, J., & Sferruzzi-Perri, A. N. (2023) · Cells · doi:10.3390/cells12050797 · Cited by 10
Asymmetric growth-limiting development of the female conceptus
Estrella, C. A. S., Gatford, K. L., Xiang, R., Javadmanesh, A., Ghanipoor-Samami, M., Nattrass, G. S., Shuaib, E., McAllister, M. Μ., Beckman, I., Thomsen, D. A., et al. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1306513 · Cited by 8
Sir Joseph Barcroft, Cambridge placental and fetal research (1933-1966) and inter-generational Science
Boyd, R. D., & Boyd, C. A. R. (2009) · The International Journal of Developmental Biology · doi:10.1387/ijdb.082762rb · Cited by 8
Human placental development
Aplin, J., & Jones, C. J. P. (2008) · Reproductive medicine and assisted reproductive techniques series · doi:10.3109/9780203091500.030 · Cited by 8
In-depth characterization of the pituitary transcriptome in Simmental and Chinese native cattle
Li, M., Lu, X., Xia, H., Zhang, C., Wang, X., Chen, Z., zhang, H., Qu, K., Huang, B., Moore, S. S., et al. (2018) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2018.09.003 · Cited by 7
Effects of Maternal Diabetes and Diet on Gene Expression in the Murine Placenta
Kappen, C., Krüger, C., & Salbaum, J. M. (2022) · Genes · doi:10.3390/genes13010130 · Cited by 7
“The labyrinth and spongiotrophoblasts strongly express Igf2, consistent with prior reports [73]; Igf2 receptor is also expressed in those areas.”
BackgroundResult
Amino Acid Supplementation Affects Imprinted Gene Transcription Patterns in Parthenogenetic Porcine Blastocysts
Park, C., Jeong, Y.-H., Jeong, Y.-I., Kwon, J., Shin, T., Hyun, S., Jeung, E., Kim, N., Seo, S.-K., Lee, C., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106549 · Cited by 7
“Imprinted genes play important roles in regulating maternal supply and fetal demand for nutrients and epigenetic changes caused by environmental conditions is required for metabolic adaptation that may render them particularly prone to unfavorable environmental factors for embryonic development [49].”
Mechanisms Underpinning Adaptations in Placental Calcium Transport in Normal Mice and Those With Fetal Growth Restriction
Hayward, C. E., McIntyre, K. R., Sibley, C. P., Greenwood, S. L., & Dilworth, M. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00671 · Cited by 7
Self-citation
The Placenta and Developmental Origins of Health and Disease
Cleal, J. K., & Lewis, R. M. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-801383-0.00022-0 · Cited by 7
Placental mTOR signalling links mitochondrial dysfunction, nutrient transport and neonatal beta cell perturbations in mice
Beetch, M., Oribamise, E. I., Jo, S., Clifton, B., Larson, S. N., Hausmann, A., Wong, A., Akhaphong, B., Morgan, E., & Alejandro, E. U. (2025) · Diabetologia · doi:10.1007/s00125-025-06542-z · Cited by 6
“For measurement of glucose flux, 3,700,000 Bq non-metabolisable 3 H-methyl-d -glucose in physiological saline was administered under isoflurane anaesthesia for 3 min [26, 27].”
mTOR is an essential gate in adapting the functional response of ovine trophoblast cells under stress-inducing environments
Viola, I., Accornero, P., Manenti, I., Miretti, S., Baratta, M., & Toschi, P. (2024) · Placenta · doi:10.1016/j.placenta.2024.09.011 · Cited by 7
Childhood trauma and insulin-like growth factors in amniotic fluid
Lamadé, E. K., Hendlmeier, F., Wudy, S. A., Blum, W. F., Witt, S. H., Rietschel, M., Coenen, M., Gilles, M., & Deuschle, M. (2021) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2021.105180 · Cited by 6
Effects of L-carnitine on reproductive performance, milk composition, placental development and IGF concentrations in blood plasma and placental chorions in sows
Zhang, S., Tian, M., Song, H., Shi, K., Wang, Y., & Guan, W. (2018) · Archives of Animal Nutrition · doi:10.1080/1745039x.2018.1471185 · Cited by 6
Mechanisms of Transfer Across the Human Placenta
Jones, R. L., Boyd, R. D., & Sibley, C. P. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4160-3479-7.10014-x · Cited by 6
Self-citation
A genetically small fetus impairs placental adaptations near term
Sandovici, I., Knee, O., López‐Tello, J., Shreeve, N., Fowden, A. L., Sferruzzi-Perri, A. N., & Constância, M. (2024) · Disease Models & Mechanisms · doi:10.1242/dmm.050719 · Cited by 5
Self-citation
Increased Placental Glucose Transport Rates in Pregnant Mice Carrying Fetuses with Targeted Disruption of Their Placental-SpecificIgf2Transcripts Are Not Associated with Raised Circulating Glucose Concentrations
Petry, C. J., Evans, M. L., Wingate, D. L., Ong, K. K., Reik, W., Constância, M., & Dunger, D. B. (2011) · Experimental Diabetes Research · doi:10.1155/2011/171376 · Cited by 5
Self-citation
Landscape of genomic imprinting and its functions in the mouse mammary gland
Xu, H., Zhao, L., Xu, F., Ma, Y., Chen, W., Zou, L., Yang, Q., Sun, J., Yu, H., & Jiao, B. (2020) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjaa020 · Cited by 5
“The functions of IGs are diverse and include nutrient transport (Slc22a2, Slc22a3, and Slc38a4) (Jonker et al., 2003; Constancia et al., 2005), signaling (Ins2 and Igf2) (Neirijnck et al.”
Background
Is small placenta a risk for low birth weight in KOKAN? (Data from a coastal region in the state of Maharashtra, India)
Patil, S. N., Dombale, V. D., Joglekar, C. V., Patil, N., Joshi, K., Warpe, B. M., & Burute, P. (2020) · Journal of Developmental Origins of Health and Disease · doi:10.1017/s2040174420000574 · Cited by 5
Maternal and Fetal PI3K-p110α Deficiency Induces Sex-Specific Changes in Conceptus Growth and Placental Mitochondrial Bioenergetic Reserve in Mice
Pereira-Carvalho, D., Salazar-Petres, E., López-Tello, J., & Sferruzzi-Perri, A. (2022) · Veterinary Sciences · doi:10.3390/vetsci9090501 · Cited by 5
Placental structure, function and mitochondrial phenotype relate to fetal size and sex in micePreprint
Salazar‐Petres, E., Carvalho, D. P., López‐Tello, J., & Sferruzzi-Perri, A. N. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.07.22.453249 · Cited by 5
Epigenetic regulation of gene expression: an overview of classical and recently discovered novel players
Rahat, B., Sharma, R., Ali, T., & Kaur, J. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-821785-6.00010-4 · Cited by 4
Placental Function in Intrauterine Growth Restriction
Chen, Y., & Jansson, T. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-35214-7.00017-2 · Cited by 4
Fetus-derived IGF2 matches placental development to fetal demandPreprint
Sandovici, I., Georgopoulou, A., Hufnagel, A., Schiefer, S., Santos, F., Hoelle, K., Lam, B., Yeo, G. S. H., Burling, K., López‐Tello, J., et al. (2019) · Research Portal (Queen's University Belfast) · doi:10.1101/520536 · Cited by 5
“We have previously proposed that imprinted genes play central roles in controlling both the fetal demand for, and the placental supply of, maternal nutrients (Constância et al., 2002, Constância et al., 2005, Coan et al., 2008, Angiolini et al., 2011).”
Self-citation
INSULIN-LIKE GROWTH FACTORS AND PLACENTAL FUNCTION
Schlabritz‐Loutsevitch, N., Li, C., & Nathanielsz, P. W. (2007) · Fetal and Maternal Medicine Review · doi:10.1017/s0965539507001994 · Cited by 3
Epigenomic Factors in Human Obesity
Bell, C. G. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-388415-2.00014-7 · Cited by 3
Maternal Stress-Mediated Gene Expression Changes in the Mouse Placenta
Longo, L. D., & Goyal, R. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-394445-0.00037-0 · Cited by 3
Promoter‐specific expression of the imprinted IGF2 gene in bovine oocytes and pre‐implantation embryos
Willhelm, B. R., Ticiani, E., Campagnolo, K., de Oliveira, G. B., de Mattos, K., Bello, C. A. P., Ongaratto, F. L., Rodríguez-Villamil, P., Relly, L., Alves, J. P. M., et al. (2021) · Reproduction in Domestic Animals · doi:10.1111/rda.13925 · Cited by 3
Sex and fetal genome influence gene expression in pig endometrium at the end of gestation
Bonnet, A., Bluy, L. E., Gress, L., Canario, L., Ravon, L., Sécula, A., Billon, Y., & Liaubet, L. (2024) · BMC Genomics · doi:10.1186/s12864-024-10144-1 · Cited by 3
“The gene encoding SLC38A3 (Solute Carrier Family 38, Member 3) was selected for its protein interaction with IGF2 (Insulin Like Growth Factor 2) [25].”
BackgroundMethod
Placental amino acid transporters
Jansson, T., & Powell, T. L. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511933806.013 · Cited by 3
Basic Experimental and Clinical Advances in the Mechanisms Underlying Abnormal Pregnancy Outcomes
Regnault, T. R. H., Nijland, M. J., Budge, H., & Morrison, J. L. (2013) · Journal of Pregnancy · doi:10.1155/2013/327638 · Cited by 3
Novel role for PI3Kβ in placental function through regulation of system A amino acid transporter expression, associated with embryonic lethality
Conduit, S., Zhang, C. X. W., Pearce, W., Guillermet-Guibert, J., Sferruzzi-Perri, A., & Vanhaesebroeck, B. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-05937-w · Cited by 2
Prenatal cannabis smoke exposure alters placental development in a murine model of pregnancy
Podinić, T., Sunil, M., MacAndrew, A., Mónaco, C., Lee, G., Lockington, C., Lucas, A.-M., Tomy, T., Kasinska, J., Jamshed, L., et al. (2026) · PLoS ONE · doi:10.1371/journal.pone.0328123 · Cited by 2
“This structural adaptation represents one of many placental compensatory mechanisms to combat environmental challenges and preserve fetal growth [95–99].”
Genomic Imprinting and Random Monoallelic Expression
Lobanova, Y., & Zhenilo, S. V. (2024) · Biochemistry (Moscow) · doi:10.1134/s000629792401005x · Cited by 2
“Igf2 is a positive regulator of embryonic growth affecting the delivery of nutrients across the placenta [4].”
Maternal Administration of the Herbal Medicine Toki-Shakuyaku-San Promotes Fetal Growth and Placental Gene Expression in Normal Mice
Li, H., Wada, E., & Wada, K. (2013) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x13500377 · Cited by 2
Male and Female Placentas Have Divergent Transcriptomic and Epigenomic Responses to Maternal Diets: Not Just Hormones
Gabory, A., Vigé, A., Ferry, L., Attig, L., Jaïs, J., Jouneau, L., & Junien, C. (2014) · Research and perspectives in endocrine interactions · doi:10.1007/978-3-319-02591-9_6 · Cited by 2
GENDER-SPECIFIC INFLUENCE OF Aу MUTATION ON PROGENY METABOLIC PHENOTYPE, FETAL GROWTH AND PLACENTAL GENE EXPRESSION IN MICE
En, M., Denisova, E. I., Kozhevnikova, V. V., & Kuleshova, A. (2018) · Vavilov Journal of Genetics and Breeding · doi:10.18699/vj18.376 · Cited by 2
Validation studies of a fluorescent method to measure placental glucose transport in mice
Kaur, H., Wilson, R. L., Care, A. S., Mühlhäusler, B. S., Roberts, C. T., & Gatford, K. L. (2019) · Placenta · doi:10.1016/j.placenta.2019.01.014 · Cited by 2
A Lack of Contact of Sperm with Accessory Sex Gland Secretions Deregulates DNA Methylation and Imprinted Gene Expression in Rodent Embryos
Poon, H. K., Lee, K. K., Wong, C. L., O, W. S., & Chow, P. H. (2009) · Systems Biology in Reproductive Medicine · doi:10.3109/19396360903165256 · Cited by 2
“Since Igf2 protein is a key factor for embryonic growth [Constancia et al. 2005], this may partly account for the larger average size of these embryos.”
Background
Genomic imprinting
Deshpande, S., Nair, S., & Balasinor, N. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819753-0.00002-7 · Cited by 2
Epigenetic change induced by in utero dietary challenge provokes phenotypic variability across multiple generations of micePreprint
de Pette, M. V., Galvão, A. M., Millership, S. J., To, W., Dimond, A., Prodani, C., McNamara, G. I., Bruno, L., Sardini, A., Webster, Z., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.07.241034 · Cited by 2
Self-citation
Fetal Endocrinology
Katugampola, H., Gevers, E. F., & Dattani, M. (2019) · Wiley eBooks · doi:10.1002/9781119152712.ch3 · Cited by 2
Longitudinal changes in gut microbiota across reproductive states in wild baboons
Southworth, C. A., Barrios, L., Dasari, M. R., Gesquiere, L. R., Gilbert, J. A., Alberts, S. C., Tung, J., & Archie, E. A. (2026) · Microbiome · doi:10.1186/s40168-026-02494-7 · Cited by 2
Placental morphofunctional adaptations and offspring outcomes after protein restriction before and during pregnancy in mice
Felicioni, F., Nivia-Riveros, J. A., Caldeira-Brant, A. L., Paula, T. D. M. D. E., Cardoso, L. C., Sales, C. F., Nogueira, J. M., Fagundes, A. M. A., Rizzo, E., Chiarini‐Garcia, H., et al. (2026) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2026.110285 · Cited by 1
Contribution of Placental Genomic Imprinting and Identification of Imprinted Genes
Kusinski, L. C., Cooper, W. N., Sandovici, I., & Constância, M. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-394445-0.00023-0 · Cited by 1
Self-citation
Some Aspects of Endocrinology of the Placenta
Longo, L. D. (2018) · Springer eBooks · doi:10.1007/978-1-4939-7483-2_9 · Cited by 1
Fisiología del crecimiento fetal
Berveiller, P. (2015) · EMC - Ginecología-Obstetricia · doi:10.1016/s1283-081x(15)71002-7 · Cited by 1
Some Aspects of the Physiology of the Placenta
Longo, L. D. (2018) · Springer eBooks · doi:10.1007/978-1-4939-7483-2_8 · Cited by 1
Evidence for two protein coding transcripts at the Igf2as locus
Duart-Garcia, C., Plattet, P., Bruggmann, R., Simillion, C., Keller, I., Andersson, G., & Braunschweig Martin, H. (2016) · Gene Reports · doi:10.1016/j.genrep.2016.04.003 · Cited by 1
Placental SLC38A4 gene polymorphisms 1304 G > A and 292 C > T, and their association with glucose > 95 mg/dl in normal weight full-term healthy newborns
Galavíz-Hernández, C., Sosa‐Macías, M., Rodríguez‐Morán, M., Martínez‐Aguilar, G., Guerrero‐Romero, F., & González‐Renteria, S. M. (2021) · Boletín Médico del Hospital Infantil de México · doi:10.24875/bmhim.20000108 · Cited by 1
Metabolic alterations induced by high maternal BMI and gestational diabetes in maternal, placental and neonatal outcomes
Martino, J. (2013) · Nottingham ePrints (University of Nottingham) · Cited by 1
Maternal Angiotensinogen Genotype and Fetal Sex Impact Uteroplacental Function and the Developmental Origins of Stress-Induced Hypertension
Hebert, J. F. (2000) · doi:10.15760/etd.6289 · Cited by 1
Developmental epigenetics in humans: Can maternal nutritional status mediate DNA methylation in their offspring?
Domínguez-Salas, P. (2013) · LSHTM Research Online (London School of Hygiene and Tropical Medicine) · doi:10.17037/pubs.04653320 · Cited by 1
“Imprinted genes control fetal and placental growth (among other things) and are involved in the adaptative response to the intra-uterine environment (232).”
Background
Growth Factor Regulation of Fetal Growth
Ham, J. N., León, D. D. D., & Katz, L. E. L. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4160-3479-7.10177-6 · Cited by 1
Fetal Requirements and Placental Transfer of Nitrogenous Compounds
Hay, W. W., Regnault, T. R. H., & Brown, L. D. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4160-3479-7.10055-2 · Cited by 1
Système IGF et croissance fœtale
Demars, J., Rossignol, S., Shmela, M. E., Netchine, I., Azzi, S., El‐Osta, A., Bouc, Y. L., & Gicquel, C. (2012) · Springer eBooks · doi:10.1007/978-2-8178-0196-4_9
Obesidad en embarazo y adolescencia: Estudio de ácidos grasos y vitaminas antioxidantes
Margni, G., & Esther, M. (2013) · TDX (Tesis Doctorals en Xarxa)
Hormonal and Physiological Changes
Derbyshire, E. J. (2011) · doi:10.1002/9781444344790.ch3
Specialized requirements
Symonds, M. E., & Ramsay, M. M. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511674792.012
Effects of maternal nutrient restriction during early or mid-gestation on bovine fetal growth, placentomes, and miRNA expression
Taylor, R. K. (2015) · TigerPrints (Clemson University)
Nutrition, environment, and epigenetics
Morison, I. M., & Reik, W. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511674792.018
Self-citation
Innate immune responses in viral hepatitis: the role of Kupffer cells and liver-derived monocytes in shaping intrahepatic immunity in mice using the LCMV infection model
Movita, D. (2014) · RePub (Erasmus University Rotterdam)
Evaluation of Placental Transport Function
Dilworth, M. R., Sibley, C. P., & Glazier, J. D. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-394445-0.00058-8
Self-citation
Molecular Aspects of Placental Development
Robinson, W. P., & McFadden, D. E. (2015) · Wiley eBooks · doi:10.1002/9781118981559.ch30
Some Aspects of the Physiology of the Placenta
Longo, L. D. (2013) · Springer eBooks · doi:10.1007/978-1-4614-7921-5_8
1 ADAPTATIONS IN PLACENTAL PHENOTYPE DEPEND ON ROUTE AND TIMING OF MATERNAL DEXAMETHASONE ADMINISTRATION IN MICE1 Running title: Placental phenotype and dexamethasone
Vaughan, O. R., Sferruzzi-Perri, A. N., Coan, P. M., & Fowden, A. L. (2016)
Self-citation
Genomic imprinting
Radford, E. J., & Ferguson‐Smith, A. C. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511933806.008
Self-citation
Mechanisms Linking Maternal Obesity to Offspring Metabolic Health
Dearden, L., & Ozanne, S. E. (2016) · Springer eBooks · doi:10.1007/978-1-4939-6386-7_8

Authors: Constância, M., Angiolini, E., Sandovici, I., Smith, P., Smith, R., Kelsey, G., Dean, W., Ferguson-Smith, A., Sibley, C. P., Reik, W., & Fowden, A.
Affiliations: Babraham Institute (GB)
Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Babraham Research Campus, Cambridge CB2 4AT, United Kingdom; Department of Anatomy, University of Cambridge, Cambridge CB2 3DY, United Kingdom; Division of Human Development, Medical School, University of Manchester, St. Mary's Hospital, Manchester M13 0JH, United Kingdom; and Department of Physiology, University of Cambridge, Cambridge CB2 3EG, United Kingdom
ORCID: Constância, Miguel
Sandovici, Ionel
Kelsey, Gavin
Dean, Wendy
Sibley, Colin P.
Reik, Wolf
Fowden, Abigail
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2005-12-19
Volume: 102
Issue: 52
Pages: 19219-19224
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0504468103
PMC: PMC1316882
OpenAlex: W2155091020
Cited by: 323
References: 34
Citations by year: 2026: 4 · 2025: 2 · 2024: 8 · 2023: 6 · 2022: 11 · 2021: 13 · 2020: 17 · 2019: 15 · 2018: 17 · 2017: 12 · 2016: 20 · 2015: 20 · 2014: 16 · 2013: 25 · 2012: 26
FWCI: 6.11
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Research Explorer (The University of Manchester) (submittedVersion)
Funders: Biotechnology and Biological Sciences Research Council (BBS/E/B/0000S119, BB/B50118X/1, S18929, S18928)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
Keywords: insulin-like growth factor II, genomic imprinting, placental nutrient transport, glucose transport, amino acid transport, GLUT3, SLC38A4, SLC38A2, system A, placental development, fetal growth, mice
MeSH terms: Alleles, Animals, Biological Transport, Female, Fetus, Genotype, Glucose, Insulin-Like Growth Factor II, Lac Operon, Mice, Inbred C57BL, Models, Genetic, Mutation, Placenta, Proteins, RNA, Messenger, Time Factors, Up-Regulation, Gene Deletion, Genomic Imprinting, Transgenes, Membrane Transport Proteins, Amino Acid Transport Systems, Amino Acid Transport System A, Glucose Transport Proteins, Facilitative, Glucose Transporter Type 3, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Adaptation of nutrient supply to fetal demand in the mouse involves interaction between the Igf2 gene and placental transporter systems

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks