Perinatal iron deficiency causes sex-dependent alterations in renal retinoic acid signaling and nephrogenesis

Perinatal iron deficiency causes sex-dependent alterations in renal retinoic acid signaling and nephrogenesis

Long-term alterations in kidney structure and function have been observed in offspring exposed to perinatal stressors such as iron deficiency (ID), albeit the mechanisms underlying these changes remain unclear. Here, we assessed how perinatal ID alters renal vitamin A metabolism, an important contri...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of nutritional biochemistry Vol. 112; p. 109227
Main Authors: Woodman, Andrew G., Mah, Richard L., Kinney, Samantha, Holody, Claudia D., Wiedemeyer, Alyssa R., Noble, Ronan M.N., Clugston, Robin D., Bourque, Stephane L.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01-02-2023
Subjects:
Animals
Female
Glial Cell Line-Derived Neurotrophic Factor
Iron - metabolism
Iron Deficiencies
Iron deficiency
Kidney
Kidney - metabolism
Male
Nephron endowment
Pregnancy
Rats
Rats, Sprague-Dawley
Renal development
Retinoic acid
Tretinoin
Vitamin A
Nephron endowment
Vitamin A
Renal development
Iron deficiency
Retinoic acid
Kidney
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Long-term alterations in kidney structure and function have been observed in offspring exposed to perinatal stressors such as iron deficiency (ID), albeit the mechanisms underlying these changes remain unclear. Here, we assessed how perinatal ID alters renal vitamin A metabolism, an important contributor to nephrogenesis, in the developing kidney. Pregnant Sprague Dawley rats were fed either an iron-restricted or -replete diet throughout gestation, and offspring were studied on postnatal day (PD)1 and 28. Maternal iron restriction results in reduced renal retinoid concentrations in male and female offspring on PD1 (P=.005). Nephron endowment was reduced by 21% in male perinatal ID offspring (P<.001), whereas it was unaffected in perinatal ID females. Perinatal ID resulted in sex-dependent changes in kidney retinoid synthesis and metabolism, whereby male offspring exhibited increased expression of Raldh2 and Rar/Rxr isoforms, while females exhibited unchanged or decreased expression (all interaction P<.05). Male perinatal ID offspring exhibit sex-specific enhancements of retinoic acid pathway signaling components on PD1, including Gdnf (P<.01) and Ctnnb1 (P<.01), albeit robust upregulation of RA transcriptional target Stra6 was observed in both sexes (P=.006). On PD28, perinatal ID resulted in elevated renal retinoid concentrations (P=.02) coinciding with enhanced expression of Raldh2 (P=.04), but not any Rar isoform or Rxr. Further, perinatal ID resulted in robust upregulation of Gdnf, Ret, Ctnnb1, associated with further increases in both Cxcr4 and Stra6 (all P<.01) at PD28. Together, these data suggest perinatal ID results in sustained sex-dependent perturbations in vitamin A metabolism, which likely underlie sex-specific reductions in nephron endowment.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0955-2863
1873-4847
DOI:10.1016/j.jnutbio.2022.109227