Hypertension and kidney alterations in rat offspring from low protein pregnancies

Villar-Martini, Veronica C; Carvalho, Jorge José de; Neves, Mário Fritsch; Águila, Márcia Barbosa; Mandarim-de-Lacerda, Carlos Alberto

doi:10.1097/01.hjh.0000358838.71675.5e

Cited by 32 publications

(25 citation statements)

References 23 publications

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“…Furthermore, vitamin A deficiency in rats results in a significant decrease in glomerular number and Ret expression, consistent with the genetic studies described above (58). In addition, maternal dietary protein restriction results in decreased nephron number, reduced renal function, and hypertension in a variety of species including rodents and sheep (75)(76)(77)(78)(79)(80). Although the precise mechanisms governing this are not well defined, there is some evidence suggesting that the maternal diet programs the expression of critical genes required for embryonic kidney development, cell survival, and renal function (76,81,82).…”

Section: In Utero Environment and Renal Hypoplasiasupporting

confidence: 65%

Genetics of Renal Hypoplasia: Insights Into the Mechanisms Controlling Nephron Endowment

et al. 2010

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ABSTRACT:Renal hypoplasia, defined as abnormally small kidneys with normal morphology and reduced nephron number, is a common cause of pediatric renal failure and adult-onset disease. Genetic studies performed in humans and mutant mice have implicated a number of critical genes, in utero environmental factors and molecular mechanisms that regulate nephron endowment and kidney size. Here, we review current knowledge regarding the genetic contributions to renal hypoplasia with particular emphasis on the mechanisms that control nephron endowment in humans and mice. R enal hypoplasia is a common, yet poorly understood and misused term describing congenital renal anomalies. Renal hypoplasia is defined as abnormally small kidneys (Ͻ2 SD below the expected mean when correlated with age or parameters of somatic growth) with normal morphology and reduced nephron number. This definition predicts that ϳ2.2% of the population exhibit renal hypoplasia, whereas epidemiologic studies suggest an estimated incidence of 1 in 400 births (1). Much confusion and the misapplication of this definition have arisen because the majority of congenitally small kidneys also exhibit evidence of tissue maldifferentiation, defined as renal dysplasia. The exact incidence of pure renal hypoplasia (without dysplasia) is difficult to define as renal dysplasia has often been incorrectly described as hypoplasia. This has predominantly been due to the lack of noninvasive diagnostic tools (i.e. Ultrasound) with resolution power adequate enough to discriminate dysplasia from hypoplasia in such settings. Severe reductions in nephron number that are characteristic of renal hypoplasia/dysplasia are the leading cause of childhood end stage renal disease. Indeed, if severe enough, these conditions can lead to significant impairment of intrauterine renal function which can in turn lead to the oligohydramnios sequence, a condition not compatible with extrauterine life. This includes severe and modest bilateral renal hypoplasia. More subtle defects in nephron number, such as those at the lower end of the normal range caused by mild bilateral renal hypoplasia, have been associated with the development of adult-onset hypertension and chronic renal failure (2-6). Here, we focus on knowledge derived from the study of human syndromic forms of renal hypoplasia and mouse mutants that provide insights into the molecular mechanisms that underlie renal hypoplasia and control nephron endowment. Congenital renal abnormalities characterized by nephron number and other renal pathologies including renal dysplasia, hydroureter, cystic dysplasia, and agenesis are reviewed in detail elsewhere (7-9). OVERVIEW OF KIDNEY DEVELOPMENTDevelopment of the mammalian metanephric kidney is dependent on reciprocal inductive interactions between two distinct cell lineages, the ureteric cell lineage and the metanephric mesenchyme (MM) cell lineage (Fig. 1). At the onset of metanephric development, signals emanating from the mass of uninduced MM initiate the formation of an epithelial bud (th...

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Section: In Utero Environment and Renal Hypoplasiasupporting

confidence: 65%

Genetics of Renal Hypoplasia: Insights Into the Mechanisms Controlling Nephron Endowment

et al. 2010

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“…Maternal protein restriction impairs various organ functions due to an important reduction of functional cells such as beta cells in pancreas (Boujendar et al, 2002), glomeruli in kidney (Villar-Martini et al, 2009), and cardiomyocytes in heart (Bezerra et al, 2008). Therefore, it programs to Type 2 diabetes, hypertension, and heart failure later in life.…”

Section: Discussionmentioning

confidence: 99%

Insights Into Coronary Artery Development in Model of Maternal Protein Restriction in Mice

Silva-Júnior

Águila

Mandarim-de-Lacerda

2011

The Anatomical Record

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Programming of fetal development is considered to be an important risk factor for noncommunicable diseases of adulthood, including coronary heart disease (CHD). Aiming to investigate the association between maternal nutrition and the development of the coronary arteries (CAs) in staged mice embryos, C57BL/6 mice embryos from Stages 16 to 23 were taken from mothers fed a normal protein (NP) or low protein (LP) diet, and the CA were studied. Although the LP embryos had lower masses, they had faster heart growth rates when compared with the NP embryos. The subepicardial plexuses were observed earlier in the NP embryos (Stage 20) than in the LP ones (Stage 22; P < 0.01). Apoptotic nuclei were seen around the aortic peritruncal ring beginning at Stage 18 in the NP and LP embryos. FLK1 þ (fetal liver kinase 1 ¼ VEGF-r2 or vascular endothelial growth factor receptor 2) cells had a homogeneous distribution in the NP embryos as early as Stage 18, whereas a similar distribution in the LP embryos was only seen at Stages 22 and 23. Maternal protein restriction in mice leads to a delay in the growth of the heart in the embryonic period modifying the development of the subepicardial peritruncal plexus and the apoptosis in the future coronary orifice region. Anat Rec, 294:1757Rec, 294: -1764Rec, 294: , 2011. V V C 2011 Wiley-Liss, Inc.

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“…92 Importantly, protein restriction causes hypertension and renal dysfunction if occurring during nephrogenesis in rats. 93,94 In addition, the remaining nephrons have thick basal membrane and structural alterations in the pedicles of podocytes, which are incapable of regenerative replication. 94 Therefore, loss of podocytes may create areas of 'bare' glomerular basement membrane, which represent potential starting points for irreversible glomerular injury.…”

Section: Programming Of Kidney Functionmentioning

confidence: 99%

“…93,94 In addition, the remaining nephrons have thick basal membrane and structural alterations in the pedicles of podocytes, which are incapable of regenerative replication. 94 Therefore, loss of podocytes may create areas of 'bare' glomerular basement membrane, which represent potential starting points for irreversible glomerular injury. 95 Fetal programming seems to be sexually dimorphic, given that female rats are relatively resistant to hypertension induced by perinatal protein restriction.…”

Section: Programming Of Kidney Functionmentioning

confidence: 99%

Developmental origins of health and disease: experimental and human evidence of fetal programming for metabolic syndrome

et al. 2011

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The concept of developmental origins of health and disease has been defined as the process through which the environment encountered before birth, or in infancy, shapes the long-term control of tissue physiology and homeostasis. The evidence for programming derives from a large number of experimental and epidemiological observations. Several nutritional interventions during diverse phases of pregnancy and lactation in rodents are associated with fetal and neonatal programming for metabolic syndrome. In this paper, recent experimental models and human epidemiological studies providing evidence for the fetal programming associated with the development of metabolic syndrome and related diseases are revisited.

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Hypertension and kidney alterations in rat offspring from low protein pregnancies

Abstract: Gestational low protein leads to glomerulogenesis retardation and consequently a lower nephron number with thick GBM and structural alterations in the pedicles of podocytes.

Cited by 32 publications

References 23 publications

Genetics of Renal Hypoplasia: Insights Into the Mechanisms Controlling Nephron Endowment

Genetics of Renal Hypoplasia: Insights Into the Mechanisms Controlling Nephron Endowment

Insights Into Coronary Artery Development in Model of Maternal Protein Restriction in Mice

Developmental origins of health and disease: experimental and human evidence of fetal programming for metabolic syndrome

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