Journal of Developmental Origins of Health and Disease

Table of Contents - 10 August 2011 - Volume 2, Issue 04  

Original Articles

Maternal undernutrition upregulates apoptosis in offspring nephrogenesis

S. A. Taftia1a, C. C. Nasta2a, M. Desaia1a3, K. E. Amayaa1, M. G. Rossa1a3 and T. R. Mageea1a3 c1

a1 Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, CA, USA

a2 Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USA

a3 Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

Abstract

Maternal undernutrition (MUN) results in growth-restricted newborns with reduced nephron numbers that is associated with increased risk of hypertension and renal disease. The total adult complement of nephrons is set during nephrogenesis suggesting that MUN affects the staged development of nephrons in as yet unknown manner. A possible cause may be the increased renal apoptosis; therefore, we investigated whether apoptotic signaling and cell death were increased in MUN rat kidneys. Pregnant rat dams were fed an ad libitum diet [control] or were 50% food restricted (MUN) starting at embryonic day (E) 10. Male offspring kidneys (n = 5 each, MUN and control) were analyzed for mRNA using quantitative PCR (E20) and for protein expression using Western blotting and immunohistochemistry (E20 and postnatal day 1, P1). Apoptosis was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Upregulation of pro-apoptotic protein expression was detected at E20 (Fas receptor, caspase 9) and at P1 (caspase 3, Bax). The anti-apoptotic factor Bcl2 was significantly decreased in P1 kidneys. Kidney TUNEL showed apoptotic nuclei significantly increased in the P1 nephrogenic zone (MUN 3.3 + 0.3 v. C 1.6 + 0.5, P = 0.002). The majority of apoptotic nuclei co-localized to mesenchyme and pretubular aggregates in the nephrogenic zone. Differential regulation of apoptosis in mesenchyme and pretubular aggregates following parturition suggests a mechanism for nephropenia in gestational programming of the kidney.

(Received December 13 2010)

(Revised May 18 2011)

(Accepted June 15 2011)

(Online publication August 10 2011)

Key words

Correspondence:

c1 Address for correspondence: Dr T. Magee, Ph.D., Assistant Professor, LA BioMed, 1124 W. Carson Street, Building RB1, RM 215, Torrance, CA 90502, USA. (Email tmagee@obgyn.humc.edu)

Footnotes

a Authors contributed equally to the work and are recognized as first co-authors.

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