Adenoviral-mediated placental gene transfer of IGF-1 corrects placental insufficiency via enhanced placental glucose transport mechanisms
Open accessAbstract
UNLABELLED: Previous work in our laboratory demonstrated that over-expression of human insulin-like growth factor -1 (hIGF-1) in the placenta corrects fetal weight deficits in mouse, rat, and rabbit models of intrauterine growth restriction without changes in placental weight. The underlying mechanisms of this effect have not been elucidated. To investigate the effect of intra-placental IGF-1 over-expression on placental function we examined glucose transporter expression and localization in both a mouse model of IUGR and a model of human trophoblast, the BeWo Choriocarcinoma cell line. METHODS: At gestational day 18, animals were divided into four groups; sham-operated controls, uterine artery branch ligation (UABL), UABL+Ad-hIGF-1 (10(8) PFU), UABL+Ad-LacZ (10(8) PFU). At gestational day 20, pups and placentas were harvested by C-section. For human studies, BeWo choriocarcinoma cells were grown in F12 complete medium +10%FBS. Cells were incubated in serum-free control media ± Ad-IGF-1 or Ad-LacZ for 48 hours. MOIs of 10∶1 and 100∶1 were utilized. The RNA, protein expression and localization of glucose transporters GLUT1, 3, 8, and 9 were analyzed by RT-PCR, Western blot and immunohistochemistry. RESULTS: In both the mouse placenta and BeWo, GLUT1 regulation was linked to altered protein localization. GLUT3, localized to the mouse fetal endothelial cells, was reduced in placental insufficiency but maintained with Ad-I GF-1 treatment. Interestingly, GLUT8 expression was reduced in the UABL placenta but up-regulated following Ad-IGF-1 in both mouse and human systems. GLUT9 expression in the mouse was increased by Ad-IGF-1 but this was not reflected in the BeWo, where Ad-IGF-1 caused moderate membrane relocalization. CONCLUSION: Enhanced GLUT isoform transporter expression and relocalization to the membrane may be an important mechanism in Ad-hIGF-1mediated correction of placental insufficiency.
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Gene therapy has been suggested as a possible candidate for treatment of FGR and has shown promise in animal models.
“Gene therapy [18] has also been suggested as a possible candidate for treatment of FGR and has shown promise in animal models.”
From Volume and vascularity: Using ultrasound to unlock the secrets of the first trimester placenta (2019) · cites this paper as [18]
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BackgroundResultInfluentialThe GLUT3 Glucose Transporter Isoform Is Differentially Expressed within Human Placental Cell Types1
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- [13]Brown K, Heller DS, Zamudio S, Illsley NP (2011) Glucose transporter 3 (GLUT3) protein expression in human placenta across gestation. Placenta. 32: 1041– 1049. 22000473 PMC3272879
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Mouse In Vivo Placental Targeted CRISPR Manipulation
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- Authors
- Jones, H. N., Crombleholme, T., & Habli, M.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- Children's Hospital Colorado (US)
- Corresponding author
- Jones, Helen N.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-09-03
- Volume
- 8
- Issue
- 9
- Pages
- e74632
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3760855
- OpenAlex
- W1994057593
- Cited by
- 64
- References
- 25
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 7 · 2022: 7 · 2021: 7 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 9 · 2016: 3 · 2015: 4 · 2014: 4
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- University of Pennsylvania
- Cincinnati Children's Hospital Medical Center
- University of Cincinnati
- National Institutes of Health (UL1TR001425, UL1TR000077)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R00HD068504, K99HD068504)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- insulin-like growth factor I, placental insufficiency, fetal growth restriction, glucose transporters, GLUT1, GLUT3, GLUT8, GLUT9, adenoviral gene transfer, BeWo choriocarcinoma cells, trophoblast, placental glucose transport
- MeSH terms
- Adenoviridae, Animals, Base Sequence, Female, Glucose, Insulin-Like Growth Factor I, Maternal-Fetal Exchange, Mice, Inbred C57BL, Placenta, Placental Insufficiency, Pregnancy, Genetic Therapy, DNA Primers, Gene Transfer Techniques, Reverse Transcriptase Polymerase Chain Reaction, Mice
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