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Differential regulation of genes for fetoplacental lipid pathways in pregnancy with gestational and type 1 diabetes mellitus
Open accessAbstract
Objective Changes in metabolic homeostasis in pregnant diabetic women are potential determinants of increased adiposity of the fetus. The aim of this study was to characterize diabetes mellitus-induced changes in genes for fetoplacental energy metabolism in relation to fetal adiposity. Study design Placentas of women with type 1 diabetes mellitus, gestational diabetes mellitus (GDM), or no complications were analyzed by microarray profiling. The pattern of gene expression was assessed in primary placental cell cultures. Results Diabetes mellitus was associated with 49 alterations in gene expression at key steps in placental energy metabolism, with 67% of the alterations related to lipid pathways and 9% of the alterations related to glucose pathways. Preferential activation of lipid genes was observed in pregnancy with GDM. Type 1 diabetes mellitus induced fewer lipid modifications but an enhancement of glycosylation and acylation pathways. Oleate enhanced expression of genes for fatty acid esterification and the formation of lipid droplets 3 times as much as glucose in cultured placental cells. Conclusion These results point to fatty acids as preferential lipogenic substrates for placental cells and suggest that genes for fetoplacental lipid metabolism are enhanced selectively in GDM. The recruited genes may be instrumental in increasing transplacental lipid fluxes and the delivery of lipid substrates for fetal use.
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“The majority of placental gene expression alterations in GDM occur in lipid pathways (67%), as compared with glucose pathways (9%) [152].”
From The Pathophysiology of Gestational Diabetes Mellitus (2018) · cites this paper as [152]
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“Preferential activation of placental lipid genes is also associated with GDM compared with T1DM [152].”
From The Pathophysiology of Gestational Diabetes Mellitus (2018) · cites this paper as [152]
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Sorted by citations
Items 101–144 of 144
Lin, L., Hua, J., Jian-Ping, H., & Yan, L. (2015) · PLoS ONE · doi:10.1371/journal.pone.0135785 · Cited by 10
Mechanisms of Fetal Overgrowth in Gestational Diabetes: The Potential Role of SOCS2
Hernández-Baraza, L., Brito‐Casillas, Y., Valverde‐Tercedor, C., Recio, C., Fernández‐Pérez, L., Guerra, B., & Wägner, A. M. (2025) · Nutrients · doi:10.3390/nu17091519 · Cited by 8
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The role of microRNAs in pregnancies complicated by maternal diabetes
Owen, M. D., Kennedy, M., Quilang, R., SCOTT, E. M., & Forbes, K. A. (2024) · Clinical Science · doi:10.1042/cs20230681 · Cited by 13
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“Some placental lipid genes are also activated during GDM [32 ].”
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“Subsequently, further research is needed to better understand the role of different TGF β isoforms in regulating glucose metabolism and energy balance in the placenta and in trophoblast cells and its potential use in protection against gestational complications.”
Mitochondrial dynamics, biogenesis, mitophagy and oxidative stress in gestational obesity: A review
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Sobrevía, L. (2013) · InTech eBooks · doi:10.5772/46133 · Cited by 26
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Serine Hydrolases in Lipid Homeostasis of the Placenta-Targets for Placental Function?
Berger, N., Allerkamp, H. H., & Wadsack, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23126851 · Cited by 5
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“This phenomenon was also confirmed by Radaelli et al([28]) They found that genes at key steps of fatty acid uptake, transport, and activation pathways were similarly up-regulated in pregnancy with GDM and type I diabetes.”
ResultDecreased serum human leukocyte antigen‐G levels are associated with gestational diabetes mellitus
Öztekin, Ö., Çabuş, Ü., & Enli, Y. (2021) · Journal of obstetrics and gynaecology research · doi:10.1111/jog.14811 · Cited by 5
Critical Importance of the Perinatal Period in the Development of Obesity
Baker, P. R., & Friedman, J. E. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1203-2_4
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Venkatesh, M. K., Shetty, S. K., & Chaithra, G. V. (2024) · Journal of South Asian Federation of Obstetrics and Gynaecology · doi:10.5005/jp-journals-10006-2389 · Cited by 2
Myo-Inositol Moderates Glucose-Induced Effects on Human Placental 13C-Arachidonic Acid Metabolism
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BackgroundEarly Origins of Health and Disease
Yzydorczyk, C., Mitanchez, D., Boubred, F., & Siméoni, U. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-800093-9.00001-6 · Cited by 3
DHA ameliorates GDM placental angiogenesis by regulating HAMP-mediated iron imbalance
Huang, Z., Zhou, S., Cui, Z., Li, J., Liu, L., Feng, X., Ye, H., Ma, K., Huang, S., Xiang, Q., et al. (2026) · Journal of Advanced Research · doi:10.1016/j.jare.2026.03.005 · Cited by 2
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“Radaelli et al, reported that, the hypothalamic-pituitarygonadal axis is disrupted in diabetic females[5].”
BackgroundKannan, P. S., Sartor, M. A., O'Connor, K. T., Neumann, J. C., Klyza, J. P., Succop, P., Wagner, B. D., Karyala, S. V., Medvedovic, M., & Menon, A. G. (2011) · Physiological Genomics · doi:10.1152/physiolgenomics.00078.2010 · Cited by 3
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“Additionally, studies have reported alterations in placental lipid metabolism among women with diabetes [37, 38].”
Masete, M., Dias, S. C., Malaza, N., Adam, S., Mutavhatsindi, H., Valverde‐Tercedor, C., Guedes, B. V., Wägner, A. M., & Pheiffer, C. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26199337
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“Studies have shown that GDM incidence is closely related to abnormal regulation of multiple genes and proteins [4,5,6], however, relatively genetic diseases have stable incidence, which cannot be used to explain the significant increased incidence in recent years.”
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Emad, D., Hassan, M., & Jabbar, A. (2026) · BULLETIN OF STOMATOLOGY AND MAXILLOFACIAL SURGERY · doi:10.58240/1829006x-2026.22.1-152
Lv, S., Lu, Y., & Jiang, P. (2025) · 3 Biotech · doi:10.1007/s13205-025-04568-z
“Additionally, in women with GDM, there is upregulation of genes associated with inflammatory pathways in the placenta may contribute to insulin resistance (Radaelli et al. 2009).”
Relationships Between Placental Lipid Transporters and Macrosomia in Healthy Pregnancy
Han, Y., Wang, C.-C., Ye, Y.-F., Ding, M.-H., Ni, L.-Y., Zheng, T., Wang, Y., Yan, H.-T., & Yang, X.-J. (2021) · doi:10.21203/rs.3.rs-146081/v1
Micronutrients Intake and Status during Pregnancy and Lactation
Brough, L., & Rees, G. (2019) · MDPI eBooks · doi:10.3390/books978-3-03897-841-1
“Moreover, it is important to mention that other nutrients, namely calcium, might decrease iron absorption, and thus observed total intakes of iron may not reflect the real iron status of our participants [43].”
BackgroundPlacental and humoral alterations in gestational diabetes
Stirm, L. (2018) · doi:10.15496/publikation-24359
“Elevated placental expression of genes involved in lipid metabolism [43, 118-120] and inflammation [119, 121-123] in obese pregnant women were proposed to be relevant for obesity-related fetal programming.”
BackgroundDifferential Gene Expression of the Placenta in Normal and Pathological Human Pregnancy
Sitras, V., & Acharya, G. (2015) · doi:10.1201/b19151-31
Effects of glucose and fatty acids interactions on glucose metabolism pathways in human trophoblasts
Franco, C. B. (2015) · ANU Open Research (Australian National University) · doi:10.25911/5d6e4af2a46b5
Prolactine placentaire et anomalies de croissance au cours du diabète maternel
Perimenis, P. (2014) · theses.fr (ABES) · doi:10.70675/2312883ezeb9cz4fb1z8e87ze7b53143e3cd
Polyunsaturated Fatty Acids and Gestational Diabetes
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Structural Characterisation of the Term Placenta: Maternal Obesity and Gestational Diabetes Mellitus
Ragonesi, L. (2017) · Queensland University of Technology · doi:10.5204/thesis.eprints.113719
“In a separate study synthesis of cholesterol and triglycerides was increased in placentae from women with GDM and obesity (Radaelli, 2009).”
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“FABP4 ▲ mRNA (birth weight > control; not macrosomic) [94] ▲ mRNA (birth weight > control; not macrosomic) [94] ▬ (no difference in birth weight) [99] ▲ (with diabetes) (birth weight > control; not macrosomic) [99] ▬ mRNA (birth weight > control; not macrosomic) [96]”
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“Maternal obesity can greatly affect the nutrient supply to the fetus because placental function is significantly affected if a mother is excessively overweight (Farley et al., 2009; Radaelli et al., 2009; Varastehpour et al., 2006).”
Background
Metadata
- Authors
- Radaelli, T., Lepercq, J., Varastehpour, A., Basu, S., Catalano, P. M., & Hauguel-De Mouzon, S.
- Affiliations
- Hôpital Cochin (FR)
- MetroHealth Medical Center (US)
- Venue
- American Journal of Obstetrics and Gynecology
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 201
- Issue
- 2
- Pages
- 209.e1-209.e10
- ISSN
- 0002-9378 (ISSN-L)
- PMC
- PMC3613858
- OpenAlex
- W2039524521
- Cited by
- 156
- References
- 46
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 8 · 2023: 10 · 2022: 7 · 2021: 10 · 2020: 10 · 2019: 4 · 2018: 13 · 2017: 14 · 2016: 11 · 2015: 11 · 2014: 10 · 2013: 13 · 2012: 8
- FWCI
- 8.81
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- American Journal of Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Case Western Reserve University
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD 22965, R01HD022965)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- gestational diabetes mellitus, type 1 diabetes, placental gene expression, fetal adiposity, placental energy metabolism, fatty acid esterification, lipid droplets, oleate, glycosylation, acylation
- MeSH terms
- Adipose Tissue, Adult, Blood Glucose, Cells, Cultured, Diabetes Mellitus, Type 1, Energy Metabolism, Female, Fetus, Homeostasis, Humans, Obesity, Placenta, Pregnancy, Diabetes, Gestational, Gene Expression Regulation, Developmental, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Lipid Metabolism
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