Exposure to Maternal Diabetes Induces Salt-Sensitive Hypertension and Impairs Renal Function in Adult Rat Offspring
- Touria Nehiri1,
- Jean-Paul Duong Van Huyen12,
- Mélanie Viltard1,
- Céline Fassot1,
- Didier Heudes12,
- Nicole Freund1,
- Georges Deschênes3,
- Pascal Houillier14,
- Patrick Bruneval12 and
- Martine Lelièvre-Pégorier1
- 1Institut 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
- 2Laboratoire d'Anatomie Pathologique, Hôpital Européen Georges Pompidou, Paris, France
- 3Service de Néphrologie Pédiatrique, Hôpital Robert Debré, Paris, France
- 4Service 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
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Published ahead of print at http://diabetes.diabetesjournals.org on 28 April 2008.
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T.N. and J.-P.D.V.H. contributed equally to this work.
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Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted April 20, 2008.
- Received June 8, 2007.
- DIABETES
