Abstract
The kidney provides an important contribution to permit the fetus to successfully transition to an independent existence by production of urine with significantly different osmolality compared with plasma. Although recent work has uncovered many aspects of the maturation and regulation of the renal concentrating and diluting mechanism, understanding of how alterations in the expression of aquaporin (AQP) water channels contribute to the formation of urine in the perinatal period is incomplete. Here, we report that both AQP-2 and -3 are expressed during fetal life as early as embryonic d 18 in ureteric buds of rat kidneys, where each is localized to the apical and basolateral membranes of epithelial cells, respectively. Northern analyses demonstrate that the 1.9-kb AQP-2 transcript is present in fetal and postnatal rat kidneys similar to that observed in adults. AQP-2 mRNA expression increases after d 3 of postnatal life. Immunoblotting reveals an increase in total kidney AQP-2 protein particularly with respect to its glycosylated form after postnatal d 3. AQP-3 protein also exhibits a similar alteration likely due to a similar increase in its glycosylation state. Both AQP-2 and AQP-3 display a distribution in the collecting ducts of human postnatal infants and adults identical to that exhibited in rat kidneys. These data show that both AQP-2 and -3 are present in collecting duct epithelia of fetal and postnatal kidneys. Thus, the reduced AVP-responsiveness and decreased urinary concentrating ability of the kidney during the fetal and immediate postnatal period does not appear to be caused by lack of AQP-2 or AQP-3 proteins.
Similar content being viewed by others

Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- IMCD:
-
inner medullary collecting duct
- P f :
-
water permeability
- E:
-
embryonic
- PN:
-
postnatal
- AQP:
-
aquaporin
References
Robillard JE, Porter CC, Jose PA 1994 Structure and function of the developing kidney. In: Holliday M, Barratt TM, Avner ED (eds) Pediatric Nephrology. Williams & Wilkins, Baltimore, pp 21–39.
Robillard JE, Matson J, Sessions C, Smith F 1979 Developmental aspects of renal tubular reabsorption of water in the lamb fetus. Pediatr Res 13: 1172–1176.
Alexander DP, Nixon DA, Widdas WF, Wohlzogen FX 1958 Gestational variations in the composition of the foetal fluids and foetal urine in the sheep. J Physiol 140: 1–13.
McCance RA, Young WF 1941 The secretion of urine by newborn infants. J Physiol 99: 265–282.
Spitzer A, Schwartz G 1992 The kidney during development. In: Windhager E (ed) Handbook of Physiology: Renal Physiology, Vol 1. Oxford University Press, New York, pp 475–544.
Heller H 1952 The action and fate of vasopressin in newborn and infant rats. J Endocrinol 8: 214–223.
Yasui M, Marples D, Belusa R, Ecklof AC, Celsi G, Nielsen S, Aperia A 1996 Development of urinary concentrating capacity: role of aquaporin-2. Am J Physiol 271:F461–F468.
Skowsky WR, Fisher D 1977 Fetal neurohypophyseal arginine vasopressin and arginine vasotocin in man and sheep. Pediatr Res 11: 627
Schubert F, George J, Rao MB 1981 Vasopressin and oxytocin content of human fetal brain at different stages of gestation. Brain Res 213: 111–117.
Ostrowski N, Young WS, Knepper M, Lolait S 1993 Expression of vasopressin V1a and V2 receptor messenger ribonucleic acid in the liver and kidney of embryonic, developing and adult rats. Endocrinology 133: 1849–1859.
Rajerison R, Butlen D, Jard S 1976 Ontogenic development of antidiuretic hormone receptors in rat kidney: comparison of hormonal binding and adenylate cyclase activation. Mol Cell Endocrinol 4: 271–285.
Schlondorff D, Weber H, Trizna W, Fine L 1978 Vasopressin responsiveness of renal adenylate cyclase in newborn rats and rabbits. Am J Physiol 3:F16–F21.
Harris HW, Zeidel M 1993 Water channels. Curr Opin Nephrol Hypertens 2: 699–707.
Denker BM, Smith BL, Kuhajda FP, Agre P 1988 Identification, purification, and partial characterization of a novel Mr 28,000 integral membrane protein from erythrocytes and renal tubules. J Biol Chem 263: 15634–15642.
Sabolic I, Valenti G, Verbatz JM, Hoek A, Verkman AS, Ausiello D, Brown D 1992 Localization of the CHIP-28 water channel in rat kidney. Am J Physiol 263:C1225–C1233.
Devuyst O, Burrow CR, Smith BL, Agre P, Knepper MA, Wilson PD 1996 Expression of aquaporins-1 and -2 during nephrogenesis and in autosomal dominant polycystic kidney disease. Am J Physiol 271:F169–F183.
Preston GM, Smith BL, Zeidel ML, Mounds JJ, Agre P 1994 Mutations in aquaporin 1 in phenotypically normal humans without functional CHIP water channels. Science 265: 1585–1587.
Smith B, Baumgarten R, Nielsen S, Raben D, Zeidel M, Agre P 1993 Concurrent expression of erythroid and renal aquaporin CHIP and appearance of water channel activity in perinatal rats. J Clin Invest 92: 2035–2041.
Yamamoto T, Sasaki S, Fushimi K, Ishibashi K, Yaoit E, Kawasaki K, Fujinaka H, Marumo F, Kihara I 1996 Expression of AQP family in rat kidneys during development and maturation. Am J Physiol 272:F198–F204.
Fushimi K, Uchida S, Hara Y, Hirata Y, Marumo F, Sasaki S 1993 Cloning and expression of apical membrane water channel of rat kidney collecting tubule N. ature 361: 549–552.
Hayashi M, Sasaki S, Tsuganezawa H, Monkawa T, Kitajima W, Konishi K, Fushimi K, Marumo F, Saruta T 1994 Expression and distribution of aquaporin of collecting duct are regulated by vasopressin V2 receptor in rat kidney. J Clin Invest 4: 1778–1783.
Nielsen S, DiGiovanni S, Christensen E, Knepper M, Harris HW 1993 Cellular and subcellular immunolocalization of vasopressin-regulated water channel in rat kidney. Proc Natl Acad Sci USA 90: 11663–11667.
Sasaki S, Fushimi K, Saito H, Saito F, Uchida S, Ishibashi K, Kuwahara M, Ikeuchi T, Inui K, Nakajima K, Watanabe T, Marumo F 1994 Cloning, characterization and chromosomal mapping of human aquaporin of collecting duct. J Clin Invest 93: 1250–1256.
Deen P, Croes H, van Aubel R, Ginsel L, van Os C 1995 Water channels encoded by mutant aquaporin-2 genes in nephrogenic diabetes insipidus are impaired in their cellular routing. J Clin Invest 95: 2291–2296.
Hayashi M, Sasaki S, Tsuganezawa H, Monkawa T, Kitajima W, Konishi K, Fushimi K, Marumo F, Saruta T 1994 Expression and distribution of aquaporin collecting duct are regulated by vasopressin V2 receptor in rat kidney. J Clin Invest 94: 1778–1783.
Sabolic I, Katsura T, Verbavatz JM, Brown D 1995 The AQP-2 water channel: Effect of vasopressin treatment, microtubule disruption and distribution in neonatal rats. J Membr Biol 143: 165–175.
Ishibashi K, Sasaki S, Fushimi K, Uchida S, Kuwahara M, Saito H, Furukawa T, Nakajima K, Yamaguchi Y, Gojobori T, Marumo F 1994 Molecular cloning and expression of a member of the aquaporin family with permeability to glycerol and urea in addition to water expressed at the basolateral membrane of kidney collecting duct cells. Proc Natl Acad Sci USA 91: 6269–6273.
Christensen BM, Olsson B, Knepper MA, Maunsbach AB, Nielsen S 1997 Cellular and subcellular localization of aquaporin-2 and aquaporin-3 in human kidney. J Am Soc Nephrol 8: 16A
Chattapadhyay N, Baum M, Bai M, Riccardi D, Hebert S, Harris HW, Brown EM 1996 Ontogeny of the extracellular calcium-sensing receptor in rat kidney. Am J Physiol 271:F736–F743.
Jo I, Harris HW, Amendt-Raduege AM, Majewski RR, Hammond TG 1995 Rat kidney papilla contains abundant synaptobrevin protein that participates in the fusion of antidiuretic hormone-regulated water channel-containing endosomes in vitro. Proc Nat Acad Sci USA 92: 1876–1880.
Elder JH, Alexander S 1982 Endo-β-N-acetylglucosaminidase F: endoglycosidase from Flavobacterium menigosepticam that cleaves both high- mannose and complex glycoproteins. Proc Natl Acad Sci USA 79: 4940–4544.
Ecelbarger C, Terris J, Frindt G, Echevarria M, Marples D, Nielsen S, Knepper M 1995 Aquaporin-3 water channel localization and regulation in rat kidney. Am J Physiol 269:F663–F672.
Uchida S, Sasaki S, Fushimi K, Marumo F 1994 Isolation of human aquaporin-CD gene. J Biol Chem 269: 23451–23455.
Robillard, J Weitzman R 1980 Developmental aspects of the fetal renal response exogenous arginine vasopressin. Am J Physiol 238:F407–F414.
Robillard J, Weitzman R, Fisher D, Smith F 1982 Developmental aspects of renal tubular reabsorption of water and fetal renal response to arginine vasopressin. In: Spitzer A (eds) The Kidney during Development: Morphology and Function. Masson, New York, pp 205–214.
Sands JM, Naruse M, Jacobs JD, Wilcox JN, Klein JD 1996 Changes in aquaporin-2 protein contribute to the urine concentrating defect in rats fed a low-protein diet. J Clin Invest 97: 2807–2814.
Terris J, Ecelbarger C, Nielsen S, Knepper M 1996 Long-term regulation of four renal aquaporins in rats. Am J Physiol 271:F414–F422.
Yamamoto T, Sasaki S, Fushimi K, Ishibashi K, Marumo F, Kihara I 1994 Subcellular localization of two types of water channels (AQP-CD and AQP-3) in the collecting duct cells of AVP-stimulated Brattelboro rats. J Am Soc Nephrol 5: 281A
Ishibashi K, Sasaki S, Fushimi K, Yamamoto T, Kuwahara M, Marumo F 1997 Immunolocalization and effect of dehydration on AQP-3, a basolateral water channel of kidney collecting ducts. Am J Physiol 272:F235–F241.
Jung JS, Preston GM, Smith BL, Guggino WP, Agre P 1994 Molecular structure of the water channel through aquaporin CHIP. The hourglass model. J Biol Chem 259: 14648–14654.
Preston GM, Jung JS, Guggino WP, Agre P 1993 The mercurial-sensitive residue at cysteine 189 in the CHIP28 water channel. J Biol Chem 268: 17–20.
Bai L, Fushimi K, Sasaki S, Marumo F 1996 Structure of aquaporin-2 vasopressin water channel. J Biol Chem 271: 5171–5176.
Baumgarten R, Wetzels J, Van Os C, Deen P 1997 Glycosylation of aquaporin-2 is not essential for routing and functioning in mammalian cells. J Am Soc Nephrol 8: 15A
Acknowledgements
The authors thank Dr. D. Ward and J. Crouse for assistance in tissue collection and sample preparation.
Author information
Authors and Affiliations
Additional information
Supported by National Institutes of Health Grants DK-38874 (H.W.H.) and DK-7268 (H.W.H.). M.B received support from a research fellowship grant from the Massachusetts Affiliate American Heart Association.
Rights and permissions
About this article
Cite this article
Baum, M., Ruddy, M., Hosselet, C. et al. The Perinatal Expression of Aquaporin-2 and Aquaporin-3 in Developing Kidney. Pediatr Res 43, 783–790 (1998). https://doi.org/10.1203/00006450-199806000-00011
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-199806000-00011
This article is cited by
-
Aquaporin1–3 expression in normal and hydronephrotic kidneys in the human fetus
Pediatric Research (2019)
-
Influence of sex on aquaporin1–4 and vasopressin V2 receptor expression in the pig kidney during development
Pediatric Research (2016)
-
Ontogeny of the mammalian kidney: expression of aquaporins 1, 2, 3, and 4
World Journal of Pediatrics (2014)

