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Maternal hypomagnesemia alters renal function but does not program changes in the cardiovascular physiology of adult offspring

  • R. N. Schlegel (a1), K. M. Moritz (a1) and T. M. Paravicini (a1) (a2)

Maternal undernutrition is known to adversely impact fetal health and development. Insults experienced in utero alter development of the fetus as it adapts to microenvironment stressors, leading to growth restriction and subsequent low birth weight. Infants born small for gestational age have significantly increased risk of developing cardiovascular and renal disease in later life, an effect that is often characterized by hypertension and reduced glomerular number. Maternal magnesium (Mg2+) deficiency during pregnancy impairs fetal growth, however, the long-term health consequences for the offspring remain unknown. Here, we used a mouse model of dietary Mg2+ deficiency before and during pregnancy to investigate cardiovascular and renal outcomes in male and female adult offspring at 6 months of age. There were no differences between groups in 24-h mean arterial pressure or heart rate as measured by radiotelemetry. Cardiovascular responses to aversive (restraint, dirty cage switch) and non-aversive (feeding response) stressors were also similar in all groups. There were no differences in nephron number, however, Mg2+-deficient offspring had increased urine flow (in both males and females) and reduced Mg2+ excretion (in males only). Despite evidence suggesting that maternal nutrient restriction programs for hypertension in adult offspring, we found that a moderate level of maternal dietary Mg2+ deficiency did not program for a nephron deficit, or alter cardiovascular function at 6 months of age. These data suggest there are no long-term adverse outcomes for the cardiovascular health of offspring of Mg2+ deficient mothers.

Corresponding author
*Address for correspondence: T. Paravicini, School of Medical Sciences, RMIT University, Bundoora, VIC 3083, Australia. (Email
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2. BM Brenner , DL Garcia , S Anderson . Glomeruli and blood pressure. Less of one, more the other? Am J Hypertens. 1988; 1, 335347.

3. DT Lackland , HE Bendall , C Osmond , BM Egan , DJ Barker . Low birth weights contribute to high rates of early-onset chronic renal failure in the Southeastern United States. Arch Intern Med. 2000; 160, 14721476.

4. BE Vikse , LM Irgens , T Leivestad , S Hallan , BM Iversen . Low birth weight increases risk for end-stage renal disease. J Am Soc Nephrol. 2008; 19, 151157.

5. NB Ojeda , D Grigore , BT Alexander . Intrauterine growth restriction: fetal programming of hypertension and kidney disease. Adv Chronic Kidney Dis. 2008; 15, 101106.

6. L Gambling , S Dunford , DI Wallace , et al. Iron deficiency during pregnancy affects postnatal blood pressure in the rat. J Physiol. 2003; 552, 603610.

8. R Goyal , LD Longo . Maternal protein deprivation: sexually dimorphic programming of hypertension in the mouse. Hypertens Res. 2013; 36, 2935.

9. SH Alwasel , N Ashton . Prenatal programming of renal sodium handling in the rat. Clin Sci. 2009; 117, 7584.

10. M Lelièvre-Pégorier , J Vilar , ML Ferrier , et al. Mild vitamin A deficiency leads to inborn nephron deficit in the rat. Kidney Int. 1998; 54, 14551462.

11. G Keller , G Zimmer , G Mall , E Ritz , K Amann . Nephron number in patients with primary hypertension. N Engl J Med. 2003; 348, 101108.

12. M Hughson , AB Farris , R Douglas-Denton , WE Hoy , JF Bertram . Glomerular number and size in autopsy kidneys: the relationship to birth weight. Kidney Int. 2003; 63, 21132122.

13. MD Hughson , R Douglas-Denton , JF Bertram , WE Hoy . Hypertension, glomerular number, and birth weight in African Americans and white subjects in the southeastern United States. Kidney Int. 2006; 69, 671678.

14. WE Hoy , MD Hughson , GR Singh , R Douglas-Denton , JF Bertram . Reduced nephron number and glomerulomegaly in Australian Aborigines: a group at high risk for renal disease and hypertension. Kidney Int. 2006; 70, 104110.

15. LL Woods , DA Weeks , R Rasch . Programming of adult blood pressure by maternal protein restriction: role of nephrogenesis. Kidney Int. 2004; 65, 13391348.

16. JR Almeida , CA Mandarim-de-Lacerda . Maternal gestational protein-calorie restriction decreases the number of glomeruli and causes glomerular hypertrophy in adult hypertensive rats. Am J Obstet Gynecol. 2005; 192, 945951.

17. CC Hoppe , RG Evans , JF Bertram , KM Moritz . Effects of dietary protein restriction on nephron number in the mouse. Am J Physiol Regul Integr Comp Physiol. 2007; 292, R1768R1774.

20. CE Parker , WJ Vivian , WH Oddy , LJ Beilin , TA Mori , TA O’Sullivan . Changes in dairy food and nutrient intakes in Australian adolescents. Nutrients. 2012; 4, 17941811.

21. P Pathak , SK Kapoor , U Kapil , SN Dwivedi . Serum magnesium level among pregnant women in a rural community of Haryana State, India. Eur J Clin Nutr. 2003; 57, 15041506.

22. RN Schlegel , JSM Cuffe , KM Moritz , TM Paravicini . Maternal hypomagnesemia causes placental abnormalities and fetal and postnatal mortality. Placenta. 2015; 36, 750758.

23. LA Cullen-McEwen , JA Armitage , JR Nyengaard , KM Moritz , JF Bertram . A design-based method for estimating glomerular number in the developing kidney. Am J Physiol Renal Physiol. 2011; 300, F1448F1453.

24. L O’Sullivan , JSM Cuffe , TM Paravicini , et al. Prenatal exposure to dexamethasone in the mouse alters cardiac growth patterns and increases pulse pressure in aged male offspring. PLoS ONE. 2013; 8, e69149.

25. D Chen , N Jancovski , JK Bassi , et al. Angiotensin type 1A receptors in C1 neurons of the rostral ventrolateral medulla modulate the pressor response to aversive stress. J Neurosci. 2012; 32, 20512061.

26. D Chen , L La Greca , GA Head , T Walther , DN Mayorov . Blood pressure reactivity to emotional stress is reduced in AT1A-receptor knockout mice on normal, but not high salt intake. Hypertens Res. 2009; 32, 559564.

27. PJ Davern , KL Jackson , TP Nguyen-Huu , L La Greca , GA Head . Cardiovascular responses to aversive and nonaversive stressors in Schlager genetically hypertensive mice. Am J Hypertens. 2010; 23, 838844.

28. PJ Davern , KL Jackson , TP Nguyen-Huu , L La Greca , GA Head . Cardiovascular reactivity and neuronal activation to stress in Schlager genetically hypertensive mice. Neuroscience. 2010; 170, 551558.

29. SH Alwasel , DJP Barker , N Ashton . Prenatal programming of renal salt wasting resets postnatal salt appetite, which drives food intake in the rat. Clin Sci. 2012; 122, 281288.

30. H Bond , K Hamilton , RJ Balment , et al. Diabetes in rat pregnancy alters renal calcium and magnesium reabsorption and bone formation in adult offspring. Diabetologia. 2005; 48, 13931400.

31. H Bond , CP Sibley , RJ Balment , N Ashton . Increased renal tubular reabsorption of calcium and magnesium by the offspring of diabetic rat pregnancy. Pediatr Res. 2005; 57, 890895.

32. MZ Mughal , JA Eelloo , SA Roberts , et al. Intrauterine programming of urinary calcium and magnesium excretion in children born to mothers with insulin dependent diabetes mellitus. Arch Dis Child Fetal Neonatal Ed. 2005; 90, F332F336.

33. KP Schlingmann , S Waldegger , M Konrad , V Chubanov , T Gudermann . TRPM6 and TRPM7–gatekeepers of human magnesium metabolism. Biochim Biophys Acta. 2007; 1772, 813821.

34. WE Hoy , MD Hughson , JF Bertram , R Douglas-Denton , K Amann . Nephron number, hypertension, renal disease, and renal failure. J Am Soc Nephrol. 2005; 16, 25572564.

35. B Cheong , R Muthupillai , MF Rubin , SD Flamm . Normal values for renal length and volume as measured by magnetic resonance imaging. Clin J Am Soc Nephrol. 2007; 2, 3845.

36. C Jean-Faucher , M Berger , C Gallon , et al. Sex-related differences in renal size in mice: ontogeny and influence of neonatal androgens. J Endocrinol. 1987; 115, 241246.

37. AL Tomat , F Inserra , L Veiras , et al. Moderate zinc restriction during fetal and postnatal growth of rats: effects on adult arterial blood pressure and kidney. Am J Physiol Regul Integr Comp Physiol. 2008; 295, R543R549.

39. SL Bourque , M Komolova , K Nakatsu , MA Adams . Long-term circulatory consequences of perinatal iron deficiency in male Wistar rats. Hypertension. 2008; 51, 154159.

40. LL Woods , JR Ingelfinger , R Rasch . Modest maternal protein restriction fails to program adult hypertension in female rats. Am J Physiol Regul Integr Comp Physiol. 2005; 289, R1131R1136.

41. KA Matthews , KL Woodall , MT Allen . Cardiovascular reactivity to stress predicts future blood pressure status. Hypertension. 1993; 22, 479485.

42. A Rozanski , JA Blumenthal , J Kaplan . Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation. 1999; 99, 21922217.

43. N Igosheva , O Klimova , T Anishchenko , V Glover . Prenatal stress alters cardiovascular responses in adult rats. J Physiol. 2004; 557, 273285.

44. L O’Sullivan , JSM Cuffe , A Koning , et al. Excess prenatal corticosterone exposure results in albuminuria, sex-specific hypotension, and altered heart rate responses to restraint stress in aged adult mice. Am J Physiol Renal Physiol. 2015; 308, F1065F1073.

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