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M Lelièvre-Pégorier

Publications and source records attributed to M Lelièvre-Pégorier.

13 recordsLinked to original sources
PubMed2003

Spatiotemporal distribution of insulin-like growth factor receptors during nephrogenesis in fetuses from normal and diabetic rats.

Exposure to hyperglycemia in utero impairs rat nephrogenesis. The effect of maternal diabetes on insulin-like growth factors and their receptors in the fetal kidney is associated with an increase in both mRNA and protein of the insulin-like growth factor II/mannose 6-phosphate receptor. However, this receptor has never been localized in the fetal kidney. The spatial and temporal distribution of the three insulin-like growth factor receptors (insulin-like growth factor I receptor, insulin-like growth factor II/mannose 6-phosphate receptor and insulin receptor) in rat metanephros during both normal and streptozotocin-induced diabetic renal development was investigated using in situ hybridization and immunohistochemistry. All receptors were found in the fetal kidney from the start of nephrogenesis. Insulin-like growth factor I receptor expression was ubiquitous and continuously present during metanephric development. Insulin receptor expression was developmentally regulated during kidney maturation with an enhanced expression in proximal tubules at the late stages of development. Insulin-like growth factor II/mannose 6-phosphate receptor expression was ubiquitous in the early stages of development and was dramatically decreased at the late stages of normal kidney development. Insulin receptor and insulin-like growth factor I receptor expressions were unchanged in diabetic metanephroi. Although the spatial expression of insulin-like growth factor II/mannose 6-phosphate receptor was unaffected by hyperglycemia, its expression was not downregulated in the mesenchyme of the nephrogenic zone of diabetic fetuses on gestational day 20. This study suggests a crucial role of insulin-like growth factor II/mannose 6-phosphate receptor in the pathogenesis of the impaired nephrogenesis in fetuses of diabetic mothers.

Animals↗
PubMed2001

Altered nephrogenesis due to maternal diabetes is associated with increased expression of IGF-II/mannose-6-phosphate receptor in the fetal kidney.

We have recently demonstrated that the exposure to hyperglycemia in utero impairs nephrogenesis in rat fetuses (Amri K et al., Diabetes 48:2240-2245, 1999). Diabetic pregnancy is commonly associated with alterations in the IGF system in fetal tissues. It has also been shown that both IGF-I and IGF-II are produced within developing metanephros and promote renal organogenesis. Therefore, we investigated the effect of maternal diabetes on IGFs and their receptors in developing fetal rat kidney. Diabetes was induced in pregnant rats by a single injection of streptozotocin on day 0 of gestation. We measured the amounts of IGF and their receptors, both proteins and mRNAs, in the metanephroi of fetuses issued from diabetic subjects and in age-matched fetuses from control subjects (14-20 days of gestation). IGF-II was produced throughout fetal nephrogenesis, whereas IGF-I protein was not detected, suggesting a critical role of IGF-II in kidney development. Fetal exposure to maternal diabetes caused no change in IGF production in the early stages of nephrogenesis. Similarly, the amounts of IGF-I receptor and insulin receptor were not altered. By contrast, there was an increase in production of IGF-II/mannose-6-phosphate receptor throughout nephrogenesis. Because this receptor plays an essential role in regulating the action of IGF-II, the altered nephrogenesis in fetuses exposed to maternal diabetes may be linked to a decrease in IGF-II bioavailability.

Animals↗
PubMed1999

Role of retinoids in renal development: pathophysiological implication.

Vitamin A closely modulates nephron endowment at birth. It is also required for the development of renal vasculature. Fetal vitamin A status may thus be responsible for most of the variations in nephron number found in the general population, and may play a major role in the intrauterine programming of chronic renal disease and hypertension.

Animals↗
PubMed1999

Mild vitamin A deficiency delays fetal lung maturation in the rat.

During late pregnancy, the fetal lung stores surfactant in preparation for extrauterine life. Surfactant deficiency, most often due to prematurity, precipitates respiratory distress syndrome (RDS) of the neonate. Although vitamin A (retinol) and retinoic acid have been shown to enhance the synthesis of phospholipid surfactant components, their effect on surfactant-specific proteins is unclear. No attempt has been made to evaluate the consequences of vitamin A restriction on surfactant phospholipid storage or on the expression of the life-essential surfactant protein-B (SP-B). We induced in rats a partial vitamin A deficiency leading to a 30-60% reduction in blood retinol, a status compatible with maintenance of gestation and absence of gross abnormalities in offspring. At term, lung surfactant phospholipids were reduced by 21%, and the major surfactant phospholipid, disaturated phosphatidylcholine (DSPC), was reduced by 27% in vitamin A-deficient (VAD) fetuses. The decrease in surfactant phospholipids and DSPC correlated linearly with plasma retinol, and reached about 50% in fetuses with the lowest retinol concentrations; it was accompanied by reduced expression of the gene for fatty acid synthase, a key enzyme in the synthetic pathway for surfactant-phospholipid lipid precursors. The amounts of SP-A, SP-B, and SP-C messenger RNAs were decreased by 46%, 32%, and 28%, respectively, in VAD fetuses. Consistently, amounts of SP-A and SP-B proteins were diminished as assessed by Western blotting. The proportion of type II cells determined after SP-B labeling was unchanged in VAD as compared with control lungs. Vitamin A deficiency is therefore a cause of lung maturational delay. In view of its rather large incidence in human populations, it may represent an increased risk for RDS and an aggravating factor for prematurity.

Animals↗
PubMed1999

Adverse effects of hyperglycemia on kidney development in rats: in vivo and in vitro studies.

Congenital malformations occur more frequently in the offspring of diabetic mothers. These in vivo and in vitro studies investigate the potential adverse effects of hyperglycemia on kidney development in the rat. Female rats were made hyperglycemic throughout gestation with a single injection of streptozotocin (STZ) on day 0 of gestation, or for a short period encompassing the early stage of renal organogenesis by infusing glucose from gestational days 12-16. Kidney development in the pups was assessed by determining the total number of nephrons formed in the kidney. The number of nephrons was significantly reduced (10-35%) in the pups from STZ-treated dams, as a function of hyperglycemia. There were also fewer nephrons in pups from dams given glucose infusion whose hyperglycemia was transiently higher on day 13 of gestation. The in vitro experiments were done on metanephroi removed from 14-day-old fetuses and grown for 6 days in medium containing 0, 6.9, 13.8, or 27.5 mmol/l glucose. The development of explants grown in 0, 13.8, and 27.5 mmol/l glucose was impaired compared with that of explants grown in the 6.9 mmol/l control medium, showing that the glucose concentration must be closely controlled to ensure optimum in vitro metanephros development. Thus, exposure to hyperglycemia in utero can cause a nephron deficit, which in turn may have renal consequences later in life.

Aging↗
PubMed1998

Mild vitamin A deficiency leads to inborn nephron deficit in the rat.

BACKGROUND: Vitamin A plays a critical role in fetal organogenesis, and its severe deficiency during pregnancy is known to result in malformations of several organs, including the kidney. However, the consequences of mild vitamin A deficiency (VAD) has received little attention. In the present study, we examined the effect of in utero exposure to mild VAD on renal organogenesis. METHODS: A rat model of mild VAD compatible with normal gestation was developed. Plasma retinol was determined by reverse phase HPLC in mothers and fetuses. Nephron counting was performed in kidneys of fetuses and pups issued from control and VAD mothers. Metanephroi explanted from 14-day-old fetuses from both groups were cultured in the presence or absence of retinoic acid (RA), and growth and differentiation were assessed. c-ret expression was analyzed from fetuses exposed in utero to VAD or to normal vitamin A status and also in metanephroi grown in culture with or without RA using RT-PCR. RESULTS: The 50% reduction in circulating vitamin A levels induced by vitamin A deprivation in pregnant rats did not affect the overall fetal development. However, the number of nephrons was reduced by 20% in 21-day-old VAD fetuses. The number of nephrons was closely correlated with circulating vitamin A level in both VAD and control fetuses. Metanephroi taken from VAD fetuses developed to a lesser extent in vitro, but their capacity to respond to exogenous retinoic acid was not altered. Finally, we found that the expression of the proto-oncogene c-ret was modulated according to the retinoid environment. CONCLUSION: We conclude that vitamin A supply to the fetus is critical in determining the number of nephrons. Data available thus far on the frequency of mild VAD during pregnancy and on the long-term consequences of inborn nephron deficit highlight the clinical relevance of the present study.

Animals↗
PubMed1998

Regulation of c-ret expression by retinoic acid in rat metanephros: implication in nephron mass control.

Vitamin A and its derivatives have been shown to promote kidney development in vitro in a dose-dependent fashion. To address the molecular mechanisms by which all-trans-retinoic acid (RA) may regulate the nephron mass, rat kidneys were removed on embryonic day 14 (E14) and grown in organ culture under standard or RA-stimulated conditions. By using RT-PCR, we studied the expression of the glial cell line-derived neurotrophic factor (GDNF), its cell surface receptor-alpha (GDNFR-alpha), and the receptor tyrosine kinase c-ret, known to play a major role in renal organogenesis. Expression of GDNF and GDNFR-alpha transcripts was high at the time of explantation and remained unaffected in culture with or without RA. In contrast, c-ret mRNA level, which was low in E14 metanephros and dropped rapidly in vitro, was increased by RA in a dose-dependent manner. The same is true at the protein level. Exogenous GDNF barely promotes additional nephron formation in vitro. Thus the present data establish c-ret as a key target of retinoids during kidney organogenesis.

Amino Acid Sequence↗
PubMed1996

Effect of 3,5,3'-triiodothyronine on maturation of rat renal phosphate transport: kinetic characteristics and phosphate transporter messenger ribonucleic acid and protein abundance.

The plasma concentration of T3 increases during the third postnatal week in rats when the young are weaned. Renal phosphate (Pi) transport matures during this period, with increases in the carrier affinity for Na-cotransported Pi(1/K(m)) and in the maximal transport rate (Vmax). As prevention of weaning prevents the normal increase in the plasma T3 concentration and blocks the maturation of Pi transport, this study examines the influence of T3 on Pi transport maturation. The brush border membranes from 21-day-old rats rendered hypothyroid with 6-n-propyl-2-thiouracil (PTU) or prevented from weaning (PW) were examined. These two treatments effectively prevented normal maturation, as the apparent K(m) was significantly higher in the PTU (0.243 +/- 0.04) and PW (0.159 +/- 0.008) rats than in controls [0.111 +/- 0.032 (n = 6; P < 0.05) and 0.104 +/- 0.005 (n = 6; P < 0.05)], and the Vmax was significantly lower [3192 +/- 170 vs. 4269 +/- 343 (n = 6; P < 0.01) and 3479 +/- 478 vs. 4184 +/- 368 (n = 6; P < 0.05)]. Administration of T3 to PTU and PW rats restored the apparent K(m) and V(max) to control values. The amounts of Na-Pi co-transporter messenger RNA and protein were also determined. The amounts of NaPi-2 messenger RNA and protein were decreased about 5-fold in PTU and PW rats, and T3 restored them to control levels. The effect of T3 on the maturation of Pi transport was independent of PTH, GH, or glucocorticoids. Thus, thyroid hormone helps control the maturation of Pi transport in the rat during weaning, and thyroid hormone may be a dominant triggering factor in this process.

Aging↗
PubMed1995

Maturation of rat renal phosphate transport: effect of triiodothyronine.

1. Prevention of weaning prevents the increase in the carrier affinity for Na(+)-cotransported phosphate (Pi) and the normal elevation of plasma 3,5,3'-triiodothyronine (T3) which occur between postnatal days 14 and 21. 2. This study examines the possible role of T3 in the control of the maturation process of Pi transport. Clearance experiments and brush-border membrane studies were performed on 14-day-old rats given T3. 3. The fractional excretion of Pi of T3-treated rats was 33% lower compared with controls (P < 0.01). After Pi perfusion, it remained at a lower level, and the amount of Pi reabsorbed per minute, corrected for the glomerular filtration rate (RPi/GFR), was higher. 4. The membrane vesicles from 14-day-old rats given T3 showed a 30% increase in carrier affinity for Na(+)-cotransported Pi. In addition to this maturational effect of T3, a 46% increase in Vmax was also observed. 5. The amount of immunoreactive Pi transporter, detected using anti-(NaPi-2) antiserum, was increased in T3-treated rats. 6. Glucose transport, another Na(+)-dependent transport system, was not altered by T3. 7. It is concluded that exogenous T3 given before the third postnatal week specifically induced precocious maturation of renal Pi transport in 14-day-old rats, suggesting that thyroid hormone is normally involved in this maturation.

Animals↗
PubMed1994

Intrauterine growth retardation leads to a permanent nephron deficit in the rat.

Intrauterine growth retardation (IUGR) was induced in Sprague-Dawley rats by partial artery ligation of one uterine horn in the mother on day 17 of gestation or by feeding the mother a 5% protein diet from day 8 of gestation. The controls were pups of the contralateral uterine horn or pups born to mothers fed a normal (22%) protein diet. The number of nephrons present at birth and the final number of nephrons in 2-week-old rats were counted throughout the entire kidney. The number of nephrons present at birth and the final number of nephrons were significantly correlated with birth weight for growth-retarded rats of both groups and their corresponding controls (P < 0.02 for the poorest correlation). Clearance experiments and morphometric studies of 2-week-old rats born to mothers with uterine artery ligation indicated that, despite a large compensatory hypertrophy of the nephrons in those animals born with a nephron deficit of about 30%, the overall renal function was impaired. We conclude that IUGR is accompanied by a nephron deficit which may not be fully compensated for within the first weeks after birth.

Animals↗
PubMed1993

Effects of weaning on phosphate transport maturation in the rat kidney. Clearance and brush border membrane studies.

Renal phosphate transport matures via an increase in the carrier affinity for phosphate during the 3rd post-natal week in the rat. This study examines whether weaning, which normally takes place during this period, plays a role in phosphate transport maturation. Early weaning (EW) and prevention of weaning (PW) both increased the fractional excretion of phosphate (EW 26.5 +/- 4.9, PW 26.7 +/- 2.2, controls 11.3 +/- 2.8, P < 0.001 and P < 0.05, n = 6 in each group). EW and PW also decreased the uptake of phosphate into brush border membrane vesicles (BBMV) isolated from the renal cortex of 21-day-old rats. Glucose transport in BBMV was not affected. The kinetics of phosphate uptake, measured in the presence of a sodium gradient, showed lower Vmax (4,112 +/- 362 pmol/mg protein per 10 s) in EW BBMV than in controls (6,030 +/- 200, n = 5, P < 0.001), but the affinity of the carrier for phosphate (1/Km) did not change. The decrease in Vmax may be due to the enhanced phosphate supply. The affinity of the carrier was lower in PW rats (Km = 0.31 +/- 0.04 mM) than in controls (0.18 +/- 0.04, n = 5, P < 0.01) but the Vmax remained unchanged. The low affinity may indicate that normal maturation of tubular transport, in which carrier affinity increases, is altered. The plasma concentrations of corticosterone, parathyroid hormone, insulin and triiodothyronine and their changes during EW and PW are also reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

The number of nephrons in the mammalian kidney: environmental influences play a determining role.

Several lines of evidence, mostly derived from animal studies, indicate that changes in the fetal environment may affect the renal development. Fetal growth retardation is associated with a nephron deficit in both humans and animals. Changes in the supply of vitamin A to the fetus may be responsible for the variations in the number of nephrons in the human kidney. In utero exposure to hyperglycemia or drugs may also cause a nephron deficit.

Animals↗