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Maternal undernutrition upregulates apoptosis in offspring nephrogenesis

Published online by Cambridge University Press:  01 August 2011

S. A. Tafti ,
C. C. Nast ,
M. Desai ,
K. E. Amaya ,
M. G. Ross  and
T. R. Magee
S. A. Tafti
Affiliation:
Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, CA, USA
C. C. Nast
Affiliation:
Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
M. Desai
Affiliation:
Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, CA, USA Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
K. E. Amaya
Affiliation:
Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, CA, USA
M. G. Ross
Affiliation:
Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, CA, USA Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
T. R. Magee*
Affiliation:
Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, CA, USA Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
*
*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 [email protected])
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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.

Keywords

gestational programmingglomerulogenesishypertensionIUGRMUN
Type
Original Articles
Information
Journal of Developmental Origins of Health and Disease , Volume 2 , Issue 4 , August 2011 , pp. 226 - 235
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2011

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Footnotes

a

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

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