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Impacts of low birthweight on kidney development and intergenerational growth of the offspring.
iScience 27:111159 (2024)
Low birthweight (LBW) increases the risk of adult-onset diseases, including kidney diseases, with intergenerational consequences; however, the underlying mechanisms and effective interventions are unclear. To examine the cross-generational effects of LBW, we established an LBW mouse model through reduced uterine perfusion pressure (RUPP) and investigated the therapeutic potential of tadalafil, a phosphodiesterase 5 inhibitor, on LBW-associated consequences. RUPP-pups (R1) had lower fetal and birth weights, delayed renal development, and fewer glomeruli than Sham-pups. In adulthood, R1 mice exhibited persistently fewer glomeruli and elevated blood pressure, while Tadalafil-R1 mice showed reduced hypertension in both sexes and improved renal pathological changes in males. Additionally, pregnant R1 mice displayed inadequate gestational liver hypertrophy, impaired hepatic purine metabolism, and diminished placental angiogenesis, resulting in fetal growth restriction in the subsequent generation. These findings underscore the lasting impact of LBW on adult health and future generations and suggest tadalafil's potential to mitigate LBW-associated risks.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Biological Sciences ; Metabolomics ; Physiology; Glomerular Number; Nephron Number; Fetal; Preeclampsia; Tadalafil; Restriction; Risk; Pregnancy; Disease; Liver
ISSN (print) / ISBN
2589-0042
e-ISSN
2589-0042
Journal
iScience
Quellenangaben
Volume: 27,
Issue: 11,
Article Number: 111159
Publisher
Elsevier
Publishing Place
Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Metabolism and Cell Death (MCD)
Grants
Laboratory Animal Pathology Platform, Common Equipment Office, Tohoku University Graduate School of Medicine
Japan Society for the Promotion of Science KAKENHI
Kawano Masanori Memorial Public Interest Incorporated Foundation
Japan Society for the Promotion of Science KAKENHI
Kawano Masanori Memorial Public Interest Incorporated Foundation