Abstract
Low birth weight is associated with adult-onset diseases including hypertension and renal disease; altered renal development after intrauterine growth restriction (IUGR) may underlie such prenatal programming. Our aim was to investigate nephron endowment and renal filtration surface area in fetal sheep in which IUGR resulted from late gestational umbilico-placental embolization (UPE) or natural twinning. UPE was performed between 120 and 140 d of gestation (term ∼147 d). At autopsy (140 d), body weights of UPE and twin fetuses were, respectively, 34% and 28% lower than controls. Kidneys were sampled using a smooth fractionator approach and glomerular number was estimated using a physical disector/fractionator technique. Glomerular capillary length and filtration surface area were estimated using unbiased stereological techniques. Although relative kidney weights (grams per kilogram body weight) were not different between groups, nephron endowment was 40% lower in twin fetuses compared with controls (34.3 ± 10.6 × 104 and 55.9 ± 19.8 × 104, respectively; p < 0.05); UPE did not alter nephron number (50.7 ± 13.2 × 104). There was no difference in the glomerular capillary length or surface area between the UPE and control fetuses. IUGR due to twinning leads to reduced nephron endowment whereas late gestational IUGR does not, suggesting that reduced nephron endowment is dependent on the timing of the growth restriction. Our findings demonstrate that reduced birth weight per se does not necessarily imply reduced nephron endowment.
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Abbreviations
- IUGR:
-
intrauterine growth restriction
- TRFSA:
-
total renal filtration surface area
- ga:
-
gestational age
- UPE:
-
umbilico-placental embolization
References
Hinchliffe SA, Lynch MR, Sargent PH, Howard CV, Van Velzen D 1992 The effect of intrauterine growth retardation on the development of renal nephrons. Br J Obstet Gynaecol 99: 296–301.
Merlet-Benichou C, Gilbert T, Muffat-Joly M, Lelievre-Pegorier M, Leroy B 1994 Intrauterine growth retardation leads to a permanent nephron deficit in the rat. Pediatr Nephrol 8: 175–180.
Zimanyi M, Bertram JF, Black MJ 2000 Nephron number in the offspring of rats fed a low protein diet during pregnancy. Image Anal Stereol 19: 219–222.
Albertsson-Wikland K, Boguszewski M, Karlberg J 1998 Children born small-for-gestational age: postnatal growth and hormonal status. Horm Res 49: ( suppl 2) 7–13.
Spencer JL, Silva DT, Snelling P, Hoy WE 1998 An epidemic of renal failure among Australian Aboriginals. Med J Aust 168: 537–541.
Gimonet V, Bussieres L, Medjebeur AA, Gasser B, Lelongt B, Laborde K 1998 Nephrogenesis and angiotensin II receptor subtypes gene expression in the fetal lamb. Am J Physiol 274:F1062–F1069.
Martin JA, Hamilton BE, Ventura SJ, Menacker F, Park MM, Sutton PD 2002 Births: final data for 2001. Natl Vital Stat Rep 51: 1–102.
Kinzler WL, Ananth CV, Vintzileos AM 2000 Medical and economic effects of twin gestations. J Soc Gynecol Investig 7: 321–327.
Cock ML, Harding R 1997 Renal and amniotic fluid responses to umbilicoplacental embolization for 20 days in fetal sheep. Am J Physiol 273:R1094–R1102.
Louey S, Cock ML, Stevenson KM, Harding R 2000 Placental insufficiency and fetal growth restriction lead to postnatal hypotension and altered postnatal growth in sheep. Pediatr Res 48: 808–814.
Bertram JF 1995 Analyzing renal glomeruli with the new stereology. Int Rev Cytol 161: 111–172.
Nyengaard JR, Marcussen N 1993 The number of glomerular capillaries estimated by an unbiased and efficient stereological method. J Microsc 171: 27–37.
Black MJ, Briscoe TA, Dunstan HJ, Bertram JF, Johnston CI 2001 Effect of angiotensin-converting enzyme inhibition on renal filtration surface area in hypertensive rats. Kidney Int 60: 1837–1843.
Nicolaides KH, Economides DL, Soothill PW 1989 Blood gases, pH, and lactate in appropriate- and small-for-gestational-age fetuses. Am J Obstet Gynecol 161: 996–1001.
Bassan H, Trejo LL, Kariv N, Bassan M, Berger E, Fattal A, Gozes I, Harel S 2000 Experimental intrauterine growth retardation alters renal development. Pediatr Nephrol 15: 192–195.
Bauer R, Walter B, Ihring W, Kluge H, Lampe V, Zwiener U 2000 Altered renal function in growth-restricted newborn piglets. Pediatr Nephrol 14: 735–739.
Bains RK, Sibbons PD, Murray RD, Howard CV, Van Velzen D 1996 Stereological estimation of the absolute number of glomeruli in the kidneys of lambs. Res Vet Sci 60: 122–125.
Levine RS, Hennekens CH, Jesse MJ 1994 Blood pressure in prospective population based cohort of newborn and infant twins. BMJ 308: 298–302.
Poulter NR, Chang CL, MacGregor AJ, Snieder H, Spector TD 1999 Association between birth weight and adult blood pressure in twins: historical cohort study. BMJ 319: 1330–1333.
Ramos-Arroyo MA, Ulbright TM, Yu PL, Christian JC 1988 Twin study: relationship between birth weight, zygosity, placentation, and pathologic placental changes. Acta Genet Med Gemellol (Roma) 37: 229–238.
Senoo M, Okamura K, Murotsuki J, Yaegashi N, Uehara S, Yajima A 2000 Growth pattern of twins of different chorionicity evaluated by sonographic biometry. Obstet Gynecol 95: 656–661.
Buck GM, Cookfair DL, Michalek AM, Nasca PC, Standfast SJ, Sever LE, Kramer AA 1989 Intrauterine growth retardation and risk of sudden infant death syndrome (SIDS). Am J Epidemiol 129: 874–884.
Hinchliffe SA, Howard CV, Lynch MR, Sargent PH, Judd BA, Van Velzen D 1993 Renal development arrest in sudden-infant-death-syndrome. Pediatr Pathol 13: 333–343.
Beech DJ, Sibbons PD, Howard CV, van Velzen D 2000 Renal developmental delay expressed by reduced glomerular number and its association with growth retardation in victims of sudden infant death syndrome and in “normal” infants. Pediatr Dev Pathol 3: 450–454.
Hoy WE, Douglas-Denton RN, Hughson MD, Cass A, Johnson K, Bertram JF 2003 A stereological study of glomerular number and volume: preliminary findings in a multiracial study of kidneys at autopsy. Kidney Int S31–S37
Hughson M, Farris AB, Douglas-Denton R, Hoy WE, Bertram JF 2003 Glomerular number and size in autopsy kidneys: the relationship to birth weight. Kidney Int 63: 2113–2122.
Marcussen N, Nyengaard JR, Christensen S 1994 Compensatory growth of glomeruli is accomplished by an increased number of glomerular capillaries. Lab Invest 70: 868–874.
Nyengaard JR 1993 Number and dimensions of rat glomerular capillaries in normal development and after nephrectomy. Kidney Int 43: 1049–1057.
Acknowledgements
The authors thank Alex Satragno for surgical assistance, Kerryn Westcott and Todd Briscoe for technical assistance, and Penelope Simmonds for the provision of the twin fetuses.
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Supported by the National Health and Medical Research Council of Australia.R.H. and M.J.B are joint senior authors.
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Mitchell, E., Louey, S., Cock, M. et al. Nephron Endowment and Filtration Surface Area in the Kidney after Growth Restriction of Fetal Sheep. Pediatr Res 55, 769–773 (2004). https://doi.org/10.1203/01.PDR.0000120681.61201.B4
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DOI: https://doi.org/10.1203/01.PDR.0000120681.61201.B4
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