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Low Birth Weight Impairs Murine Kidney Development and Function
Author(s) -
Ratliff Brian,
Pawar Rahul,
Aldumuahdhi Wasan,
Nnoli Oluwadara,
Zullo Joseph,
Rabadi May
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1222.4
Subject(s) - low birth weight , gestation , offspring , renal function , kidney , birth weight , kidney development , medicine , progenitor cell , endocrinology , biology , physiology , andrology , pregnancy , stem cell , biochemistry , genetics , embryonic stem cell , gene
Background The low birth weight (LBW) neonate is at greater risk for morbidity and mortality after birth and during adulthood. Methods Using immunohistochemistry, immunofluorescence, PCR, Laser‐Doppler flowmetry, and ELISA assay, we examined survival, kidney development and function, and circulating levels of pro‐inflammatory cyto‐/chemokines in the LBW offspring of malnourished (caloric and protein restricted) pregnant mice. Results Maternal malnourishment during gestation led to LBW newborns (40% reduced body weight) with only 46% of these babies surviving the first week after birth. The LBW neonate had elevated serum creatinine, while kidney blood perfusion was reduced by 26%. During gestation the LBW offspring suffered a severe impairment in nephrogenesis, due to a 76% drop in renal vesicle formation that was characterized by a 2.2‐fold increase in apoptosis, a 75% decrease in six2 positive nephron progenitor cells, and a 27% decrease in expression of the renal mesenchymal‐to‐epithelial signaling factor Wnt9b. At the conclusion of nephrogenesis, the LBW neonate had 36% fewer nephrons than controls. At birth, the LBW neonate had elevated plasma levels of IL‐1, IL‐12(p70) and GM‐CSF, further impairing six2 positive progenitor cell competence and nephrogenesis. Conclusion The kidneys of LBW neonates are underdeveloped, thereby predisposing the neonate to adverse health problems. Support or Funding Information Studies were supported by AHA grant 12SDG9080006, ASN grant 010973‐101 and The New York Community Trust‐Renal Clinical Fund (BBR)