Exposure to Maternal Diabetes Induces Salt-Sensitive Hypertension and Impairs Renal Function in Adult Rat Offspring
Touria Nehiri 1 ,
Jean-Paul Duong Van Huyen 1 2 ,
Mélanie Viltard 1 ,
Céline Fassot 1 ,
Didier Heudes 1 2 ,
Nicole Freund 1 ,
Georges Deschênes 3 ,
Pascal Houillier 1 4 ,
Patrick Bruneval 1 2 and
Martine Lelièvre-Pégorier 1
1 Institut National de la Santé et de la Recherche Médicale, Unite Mixte de Recherche S872, Centre de Recherche des Cordeliers,
Paris, France; Université Paris Descartes, Unite Mixte de Recherche S872, Paris, France; Université Pierre et Marie Curie-Paris
6, Unite Mixte de Recherche S872, Paris, France
2 Laboratoire d'Anatomie Pathologique, Hôpital Européen Georges Pompidou, Paris, France
3 Service de Néphrologie Pédiatrique, Hôpital Robert Debré, Paris, France
4 Service de d'Explorations Fonctionelles, Hôpital Européen Georges Pompidou, Paris, France
Corresponding author: Martine Lelièvre-Pégorier, martine.lelievre-pegorier{at}crc.jussieu.fr
Abstract
OBJECTIVE— Epidemiological and experimental studies have led to the hypothesis of fetal origin of adult diseases, suggesting that some
adult diseases might be determined before birth by altered fetal development. We have previously demonstrated in the rat that
in utero exposure to maternal diabetes impairs renal development leading to a reduction in nephron number. Little is known
on the long-term consequences of in utero exposure to maternal diabetes. The aim of the study was to assess, in the rat, long-term
effects of in utero exposure to maternal diabetes on blood pressure and renal function in adulthood.
RESEARCH DESIGN AND METHODS— Diabetes was induced in Sprague-Dawley pregnant rats by streptozotocin on day 0 of gestation. Systolic blood pressure, plasma
renin activity, and renal function were measured in the offspring from 1 to 18 months of age. High-salt diet experiments were
performed at the prehypertensive stage, and the abundance of tubular sodium transporters was evaluated by Western blot analysis.
Kidney tissues were processed for histopathology and glomerular computer-assisted histomorphometry.
RESULTS AND CONCLUSIONS— We demonstrated that in utero exposure to maternal diabetes induces a salt-sensitive hypertension in the offspring associated
with a decrease in renal function in adulthood. High-salt diet experiments show an alteration of renal sodium handling that
may be explained by a fetal reprogramming of tubular functions in association or as a result of the inborn nephron deficit
induced by in utero exposure to maternal diabetes.
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 28 April 2008.
T.N. and J.-P.D.V.H. contributed equally to this work.
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10.2337/db07-0780