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Sekimoto, A.* ; Takaso, Y.* ; Saruyama, H.* ; Ookawa, M.* ; Yamamoto, M.* ; Toyohara, T.* ; Saigusa, D.* ; Fukuuchi, T.* ; Otsuka, M.* ; Fushiki, Y.* ; Yamakoshi, S.* ; Tanaka, K.* ; Ikeda, T.* ; Tanaka, T.* ; Takahashi, N.* ; Mishima, E. ; Sato, E.*

Impacts of low birthweight on kidney development and intergenerational growth of the offspring.

iScience 27:111159 (2024)
Publ. Version/Full Text DOI PMC
Open Access Gold
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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
Language english
Publication Year 2024
HGF-reported in Year 2024
ISSN (print) / ISBN 2589-0042
e-ISSN 2589-0042
Journal iScience
Quellenangaben Volume: 27, Issue: 11, Pages: , Article Number: 111159 Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Reviewing status Peer reviewed
Institute(s) Institute of Metabolism and Cell Death (MCD)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Genetics and Epidemiology
PSP Element(s) G-506900-001
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
DOI 10.1016/j.isci.2024.111159
WOS ID 001347828800001
Scopus ID 85207746047
PubMed ID 39524353
Erfassungsdatum 2024-11-07
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