Hostname: page-component-76fb5796d-45l2p Total loading time: 0 Render date: 2024-04-25T13:49:14.270Z Has data issue: false hasContentIssue false
  • English
  • Français

Ovine fetal renal development impacted by multiple fetuses and uterine space restriction

Published online by Cambridge University Press:  18 July 2013

K. M. Meyer-Gesch ,
M. Y. Sun ,
J. M. Koch ,
J. Ramadoss ,
S. E. Blohowiak ,
R. R. Magness  and
P. J. Kling
K. M. Meyer-Gesch
Affiliation:
Departments of Pediatrics, University of Wisconsin, Madison, WI 53715, USA Animal Sciences, University of Wisconsin, Madison, WI 53715, USA Obstetrics and Gynecology, Perinatal Research Laboratory, University of Wisconsin, Madison, WI 53715, USA
M. Y. Sun
Affiliation:
Departments of Pediatrics, University of Wisconsin, Madison, WI 53715, USA Obstetrics and Gynecology, Perinatal Research Laboratory, University of Wisconsin, Madison, WI 53715, USA
J. M. Koch
Affiliation:
Obstetrics and Gynecology, Perinatal Research Laboratory, University of Wisconsin, Madison, WI 53715, USA
J. Ramadoss
Affiliation:
Obstetrics and Gynecology, Perinatal Research Laboratory, University of Wisconsin, Madison, WI 53715, USA UTMB-Galveston, Galveston, TX, USA
S. E. Blohowiak
Affiliation:
Departments of Pediatrics, University of Wisconsin, Madison, WI 53715, USA
R. R. Magness
Affiliation:
Departments of Pediatrics, University of Wisconsin, Madison, WI 53715, USA Animal Sciences, University of Wisconsin, Madison, WI 53715, USA Obstetrics and Gynecology, Perinatal Research Laboratory, University of Wisconsin, Madison, WI 53715, USA
P. J. Kling*
Affiliation:
Departments of Pediatrics, University of Wisconsin, Madison, WI 53715, USA
*
Address for correspondence: P. J. Kling, Department of Pediatrics, University of Wisconsin, 202 S. Park St., Neonatology Divsision, Madison 53715, USA. Email pkling@pediatrics.wisc.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

Intrauterine growth restriction (IUGR) from uteroplacental dysfunction causes impaired nephrogenesis and ultimately hypertension, but it is unknown whether IUGR caused by insufficient space for placental development seen in uterine anomalies and/or multifetal gestation exerts the same effects. Fetal renal development and metabolism were studied in an ovine space-restriction model by combining unilateral horn surgical ligation and/or multifetal gestation. Reduced placental attachment sites and placental weight per fetus defined space-restricted (USR) v. control nonrestricted (NSR) fetuses. Space-restricted fetuses exhibited evidence for decreased plasma volume, with higher hematocrit and plasma albumin at gestational day (GD) 120, followed by lower blood pO2, and higher osmolarity and creatinine at GD130, P < 0.05 for all. By combining treatments, fetal kidney weight relative to fetal weight was inversely related to both fetal weight and plasma creatinine levels, P < 0.05 for both. At GD130, space-restricted fetal kidney weights, cortical depths and glomerular generations were decreased, P < 0.05 for all. Space-restricted kidneys underwent an adaptive response by prolonging active nephrogenesis and increasing maculae densa number, P < 0.05 for both. The major renal adaptations in space-restricted IUGR fetuses included immaturity in both development and endocrine function, with evidence for impaired renal excretory function.

Keywords

IUGR, renal development, uterine space restriction
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 4 , Issue 5 , October 2013 , pp. 411 - 420
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Brenner, MK. Gene transfer to hematopoietic cells. N Engl J Med. 1996; 335, 337–339.CrossRefGoogle ScholarPubMed
2.Schreuder, M, Delemarre-van de Waal, H, van Wijk, A. Consequences of intrauterine growth restriction for the kidney. Kidney Blood Press Res. 2006; 29, 108–125.CrossRefGoogle ScholarPubMed
3.Wintour, EM, Johnson, K, Koukoulas, I, et al. Programming the cardiovascular system, kidney and the brain – a review. Placenta. 2003; 24, S65–S71.CrossRefGoogle ScholarPubMed
4.Douglas-Denton, R, Moritz, KM, Bertram, JF, Wintour, EM. Compensatory renal growth after unilateral nephrectomy in the ovine fetus. J Am Soc Nephrol. 2002; 13, 406–410.CrossRefGoogle ScholarPubMed
5.Bergvall, N, Iliadou, A, Johansson, S, et al. Genetic and shared environmental factors do not confound the association between birth weight and hypertension: a study among Swedish twins. Circulation. 2007; 115, 2931–2938.CrossRefGoogle Scholar
6.de Geus, EJ, Posthuma, D, Ijzerman, RG, Boomsma, DI. Comparing blood pressure of twins and their singleton siblings: being a twin does not affect adult blood pressure. Twin Res. 2001; 4, 385–391.CrossRefGoogle Scholar
7.Eriksson, M, Sartono, E, Martins, CL, et al. A comparison of ex vivo cytokine production in venous and capillary blood. Clin Exp Immunol. 2007; 150, 469–476.CrossRefGoogle ScholarPubMed
8.Romo, A, Carceller, R, Tobajas, J. Intrauterine growth retardation (IUGR): epidemiology and etiology. Pediatr Endocrinol Rev. 2009; 6(Suppl 3), 332–336.Google ScholarPubMed
9.Reichman, D, Laufer, MR, Robinson, BK. Pregnancy outcomes in unicornuate ueri: a review. Fertil Steril. 2009; 91, 1886–1894.CrossRefGoogle Scholar
10.Meyer, KM, Koch, JM, Ramadoss, J, Kling, PJ, Magness, RR. Ovine surgical model of uterine space restriction: interactive effects of uterine anomalies and multifetal gestations on fetal and placental growth. Biol Reprod. 2010; 83, 799–806.CrossRefGoogle ScholarPubMed
11.Sun, MY, Habeck, JM, Meyer, KM, et al. Ovine uterine space restriction alters placental transferrin receptor and fetal iron status during late pregnancy. Pediatr Res. 2013; 73, 277–285.CrossRefGoogle ScholarPubMed
12.Morrison, JL. Sheep models of intrauterine growth restriction: fetal adaptations and consequences. Clin Exp Pharmacol Physiol. 2008; 35, 730–743.CrossRefGoogle ScholarPubMed
13.Fomon, SJ. Iron. In Nutrition of Normal Infants (ed. Fomon S), 1993; pp. 239–260. Mosby: St. Louis.Google Scholar
14.Widness, JA, Garcia, JF, Clemons, GK, et al. Temporal response of immunoreactive erythropoietin to acute hypoxemia in the sheep fetus. Pediatr Res. 1986; 20, 15–19.CrossRefGoogle Scholar
15.Rodriguez, MM, Gomez, A, Abitbol, CL, et al. Comparative renal histomorphometry: a case study of oligonephropathy of prematurity. Pediatr Nephrol. 2005; 20, 945–949.CrossRefGoogle ScholarPubMed
16.Drake, KA, Sauerbry, MJ, Blohowiak, SE, Repyak, KS, Kling, PJ. Iron deficiency and renal development in the newborn rat. Pediatr Res. 2009; 66, 619–624.CrossRefGoogle ScholarPubMed
17.Neuman, RB, Unal, ER. Multiple gestations: timing of indicated late preterm and early-term births in uncomplciated dichorionic, monochorionic, and monoamniotic twins. Semin Perinatol. 2011; 35, 277–285.CrossRefGoogle Scholar
18.Gibson, KJ, Lumbers, ER. Effects of bilateral nephrectomy and angiotensin II replacement on body fluids in foetal sheep. Clin Exp Pharmacol Physiol. 1999; 26, 765–773.CrossRefGoogle ScholarPubMed
19.Ross, MG, Desai, M, Guerra, C, Wang, S. Prenatal programming of hypernatremia and hypertension in neonatal lambs. Am J Physiol Regul Integr Comp Physiol. 2005; 288, R97–R103.CrossRefGoogle ScholarPubMed
20.Nicolaides, KH, Thilaganathan, B, Mibashan, RS. Cordocentesis in the investigation of fetal erythropoiesis. Am J Obstet Gynecol. 1989; 161, 1197–1200.CrossRefGoogle ScholarPubMed
21.Jensen, OH. Doppler velocimetry and umbilcal cord blood gass assessment of twins. Eur J Obstet Gynecol Reprod Biol. 1993; 49, 155–159.CrossRefGoogle Scholar
22.Gagnon, R, Harding, R, Brace, RA. Amniotic fluid and fetal urinary responses to severe placental insufficiency in sheep. Am J Obstet Gynecol. 2002; 186, 1076–1084.CrossRefGoogle ScholarPubMed
23.Tan, C, Eckardt, K-U, Firth, JD, Ratcliffe, PJ. Feedback modulation of renal and hepatic erythropoietin mRNA in response to graded anemia and hypoxia. Am J Physiol. 1992; 263, F474–F481.Google ScholarPubMed
24.Stojanovic, V, Vuckovic, N, Spasojevic, S, et al. The influence of EPO and hypothermia on the kidneys of rats after perinatal asphyxia. Pediatr Nephrol. 2012; 27, 139–144.CrossRefGoogle ScholarPubMed
25.Moore, E, Bellomo, R. Erythropoietin (EPO) in acute kidney injury. Ann Intensive Care. 2011; 1, 3.CrossRefGoogle ScholarPubMed
26.Kling, PJ, Dragsten, PR, Roberts, A, et al. Iron deprivation increases erythropoietin production in vitro, in normal subjects and patients with malignancy. Brit J Haematol. 1996; 95, 241–248.CrossRefGoogle ScholarPubMed
27.Saito, K, Ishizaka, N, Aizawa, T, et al. Role of aberrant iron homeostasis in the upregulation of transforming growth factor-B1 in the kidney of angiotensin II-induced hypertensive rats. Hypertens Res. 2004; 27, 599–607.CrossRefGoogle Scholar
28.Ishizaka, N, Saito, K, Furuta, K, et al. Angiotensin II-induced regulation of the expression and localization of iron metabolism-related genes in the rat kidney. Hypertens Res. 2007; 30, 195–202.CrossRefGoogle ScholarPubMed
29.Smith, CP, Thevenod, F. Iron transport and the kidney. Biochim Biophys Acta. 2009; 1790, 724–730.CrossRefGoogle ScholarPubMed
30.Sebire, NJ, Jain, V, Talbert, DG. Spiral artery associated restricted growth (SPAARG): a computer model of pathophysiology resulting from low intervillous pressure having fetal programming implications. Pathophysiology. 2004; 11, 87–94.CrossRefGoogle ScholarPubMed
31.Yoshimura, T, Magness, RR, Rosenfeld, CR. Angiotensin II and alpha-angonist. I. Responses of ovine fetoplacental vasculature. Am J Physiol. 1990; 259, H464–H472.Google ScholarPubMed
32.Wang, S, Chen, J, Kallichanda, N, et al. Prolonged prenatal hypernatremia alters neuroendocrine and electrolyte homeostasis in neonatal sheep. Exp Biol Med (Maywood). 2003; 228, 41–45.CrossRefGoogle ScholarPubMed
33.Mansano, R, Desai, M, Garg, A, Choi, GY, Ross, MG. Enhanced nephrogenesis in offspring of water-restricted rat dams. Am J Obstet Gynecol. 2007; 196, e481–e486.CrossRefGoogle ScholarPubMed
34.Fisher, M, Gokhman, I, Pick, U, Zamir, A. A structurally novel transferrin-like protein accumulates in the plasma membrane of the unicellular green alga Dunaliella salina grown in high salinities. J Biol Chem. 1997; 272, 1565–1570.CrossRefGoogle ScholarPubMed
35.Moritz, KM, Wintour, EM. Functional development of the meso- and metanephros. Pediatr Nephrol. 1999; 13, 171–178.CrossRefGoogle ScholarPubMed
36.Botting, KJ, Wang, KC, Padhee, M, et al. Early origins of heart disease: low birth weight and determinants of cardiomyocyte endowment. Clin Exp Pharmacol Physiol. 2012; 39, 814–823.CrossRefGoogle ScholarPubMed
37.McMillen, IC, Adams, MB, Ross, JT, et al. Fetal growth restriction: adaptations and consequences. Reproduction. 2001; 122, 195–204.CrossRefGoogle ScholarPubMed
38.Bertram, JF. Counting in the kidney. Kidney Int. 2001; 59, 792–796.CrossRefGoogle ScholarPubMed
39.Mitchell, EK, Louey, S, Cock, ML, Harding, R, Black, MJ. Nephron endowment and filtration surface area in the kidney after growth restriction of fetal sheep. Pediatr Res. 2004; 55, 769–773.CrossRefGoogle ScholarPubMed
40.Muhle, A, Muhle, C, Amann, K, et al. No juvenile arterial hypertension in sheep multiples despite reduced nephron numbers. Pediatr Nephrol. 2010; 25, 1653–1661.CrossRefGoogle ScholarPubMed
41.Bagby, SP. Maternal nutrition, low nephron number, and hypertension in later life: pathways of nutritional programming. J Nutr. 2007; 137, 1066–1072.CrossRefGoogle ScholarPubMed
42.Moritz, KM, Cuffe, JS, Wilson, LB, et al. Review: Sex specific programming: a critical role for the renal renin-angiotensin system. Placenta. 2010; 31(Suppl), S40–S46.CrossRefGoogle ScholarPubMed
43.Pesce, C. Glomerular number and size: facts and artifacts. Anat Rec. 1998; 251, 66–71.3.0.CO;2-9>CrossRefGoogle Scholar
44.Zhang, DY, Lumbers, ER, Simonetta, G, et al. Effects of placental insufficiency on the ovine fetal renin-angiotensin system. Exp Physiol. 2000; 85, 79–84.Google ScholarPubMed
45.Daikha-Dahmane, F, Levy-Beff, E, Jugie, M, Lenclen, R. Foetal kidney maldevelopment in maternal use of angiotensin II type I receptor antagonists. Pediatr Nephrol. 2006; 21, 729–732.CrossRefGoogle ScholarPubMed
46.Komlosi, P, Fintha, A, Bell, PD. Unraveling the relationship between macula densa cell volume and luminal solute concentration/osmolality. Kidney Int. 2006; 70, 865–871.CrossRefGoogle ScholarPubMed
47.Razga, Z, Nyengaard, JR. The effect of angiotensin II on the number of macula densa cells through the AT1 receptor. Nephron Physiol. 2009; 112, 37–43.CrossRefGoogle ScholarPubMed
48.Zohdi, V, Moritz, KM, Bubb, KJ, et al. Nephrogenesis and the renal renin-angiotensin system in fetal sheep: effects of intrauterine growth restriction during late gestation. Am J Physiol Regul Integr Comp Physiol. 2007; 293, R1267–R1273.CrossRefGoogle ScholarPubMed
Supplementary material: PDF

Meyer-Gesch Supplementary Material

Appendix

Download Meyer-Gesch Supplementary Material(PDF)
PDF 113.1 KB