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Nutrition & Metabolism
Published in: Nutrition & Metabolism 1/2023

Open Access 01-12-2023 | Intrauterine Growth Restriction | Research

Intrauterine growth restriction alters kidney metabolism at the end of nephrogenesis

Authors: Sheng-Yuan Ho, Merryl Esther Yuliana, Hsiu-Chu Chou, Chung-Ming Chen

Published in: Nutrition & Metabolism | Issue 1/2023

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Abstract

Background

This study investigated the effect of uteroplacental insufficiency (UPI) on renal development by detecting metabolic alterations in the kidneys of rats with intrauterine growth restriction (IUGR).

Methods

On gestational day 17, pregnant Sprague Dawley rats were selected and allocated randomly to either the IUGR group or the control group. The IUGR group received a protocol involving the closure of bilateral uterine vessels, while the control group underwent a sham surgery. The rat pups were delivered on gestational day 22 by natural means. Pups were randomly recruited from both the control and IUGR groups on the seventh day after birth. The kidneys were surgically removed to conduct Western blot and metabolomic analyses.

Results

IUGR was produced by UPI, as evidenced by the significantly lower body weights of the pups with IUGR compared to the control pups on postnatal day 7. UPI significantly increased the levels of cleaved caspase-3 (p < 0.05) and BAX/Bcl-2 (p < 0.01) in the pups with IUGR. Ten metabolites exhibited statistically significant differences between the groups (q < 0.05). Metabolic pathway enrichment analysis demonstrated statistically significant variations between the groups in the metabolism related to fructose and mannose, amino and nucleotide sugars, and inositol phosphate.

Conclusions

UPI alters kidney metabolism in growth-restricted newborn rats and induces renal apoptosis. The results of our study have the potential to provide new insights into biomarkers and metabolic pathways that are involved in the kidney changes generated by IUGR.
Appendix
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Literature
1.
Sharma D, Shastri S, Farahbakhsh N, Sharma P. Intrauterine growth restriction—part 1. J Matern Fetal Neonatal Med. 2016;29:3977–87.CrossRefPubMed
2.
Eriksson JG, Salonen MK, Kajantie E, Osmond C. Prenatal growth and CKD in older adults: longitudinal findings from the Helsinki Birth Cohort Study, 1924–1944. Am J Kidney Dis. 2018;71:20–6.CrossRefPubMed
3.
Vikse BE, Irgens LM, Leivestad T, Hallan S, Iversen BM. Low birth weight increases risk for end-stage renal disease. J Am Soc Nephrol. 2008;19:151–7.CrossRefPubMedPubMedCentral
4.
Henriksen T, Clausen T. The fetal origins hypothesis: placental insufficiency and inheritance versus maternal malnutrition in well-nourished populations. Acta Obstet Gynecol Scand. 2002;81:112–4.CrossRefPubMed
5.
Cox P, Marton T. Pathological assessment of intrauterine growth restriction. Best Pract Res Clin Obstet Gynaecol. 2009;23:751–64.CrossRefPubMed
6.
Janot M, Cortes-Dubly ML, Rodriguez S, Huynh-Do U. Bilateral uterine vessel ligation as a model of intrauterine growth restriction in mice. Reprod Biol Endocrinol. 2014;12:62.CrossRefPubMedPubMedCentral
7.
Stewart T, Kallash M, Vehaskari VM, Hodgeson SM, Aviles DH. Increased autophagy and apoptosis in the kidneys of intrauterine growth restricted rats. Fetal Pediatr Pathol. 2019;38:185–94.CrossRefPubMed
8.
Montaldo P, Puzone S, Caredda E, Pugliese U, Inserra E, Cirillo G, Gicchino F, Campana G, Ursi D, Galdo F, et al. Impact of intrauterine growth restriction on cerebral and renal oxygenation and perfusion during the first 3 days after birth. Sci Rep. 2022;12:5067.CrossRefPubMedPubMedCentral
9.
Yi CH, Vakifahmetoglu-Norberg H, Yuan J. Integration of apoptosis and metabolism. Cold Spring Harb Symp Quant Biol. 2011;76:375–87.CrossRefPubMed
10.
Cuffe JSM, Briffa JF, Rosser S, Siebel AL, Romano T, Hryciw DH, Wlodek ME, Moritz KM. Uteroplacental insufficiency in rats induces renal apoptosis and delays nephrogenesis completion. Acta Physiol (Oxf). 2018;222:e12982.CrossRef
11.
Nüsken E, Fink G, Lechner F, Voggel J, Wohlfarth M, Sprenger L, Mehdiani N, Weber LT, Liebau MC, Brachvogel B, Dötsch J, Nüsken KD. Altered molecular signatures during kidney development after intrauterine growth restriction of different origins. J Mol Med (Berl). 2020;98:395–407.CrossRefPubMed
12.
Seely JC. A brief review of kidney development, maturation, developmental abnormalities, and drug toxicity: juvenile animal relevancy. J Toxicol Pathol. 2017;30:125–33.CrossRefPubMedPubMedCentral
13.
Nyengaard JR. The quantitative development of glomerular capillaries in rats with special reference to unbiased stereological estimates of their number and sizes. Microvasc Res. 1993;45:243–61.CrossRefPubMed
14.
Schmitt R, Ellison DH, Farman N, Rossier BC, Reilly RF, Reeves WB, Oberbäumer I, Tapp R, Bachmann S. Developmental expression of sodium entry pathways in rat nephron. Am J Physiol. 1999;276:F367-381.PubMed
15.
16.
Priante E, Verlato G, Stocchero M, Giordano G, Pirillo P, Bonadies L, Visentin S, Moschino L, Baraldi E. Metabolomic profiling of intrauterine growth-restricted preterm infants: a matched case-control study. Pediatr Res. 2022;93:1599–608.
17.
Huang LT, Chou HC, Lin CM, Chen CM. Uteroplacental insufficiency alters the retinoid pathway and lung development in newborn rats. Pediatr Neonatol. 2016;57:508–14.CrossRefPubMed
18.
Chahoud I, Paumgartten FJ. Influence of litter size on the postnatal growth of rat pups: is there a rationale for litter-size standardization in toxicity studies? Environ Res. 2009;109:1021–7.CrossRefPubMed
19.
OECD: Test No. 421: reproduction/developmental toxicity screening test. 2016.
20.
Gibson CL, Codreanu SG, Schrimpe-Rutledge AC, Retzlaff CL, Wright J, Mortlock DP, Sherrod SD, McLean JA, Blakely RD. Global untargeted serum metabolomic analyses nominate metabolic pathways responsive to loss of expression of the orphan metallo β-lactamase, MBLAC1. Mol Omics. 2018;14:142–55.CrossRefPubMedPubMedCentral
21.
22.
Feng Q, Liu Z, Zhong S, Li R, Xia H, Jie Z, Wen B, Chen X, Yan W, Fan Y, et al. Integrated metabolomics and metagenomics analysis of plasma and urine identified microbial metabolites associated with coronary heart disease. Sci Rep. 2016;6:22525.CrossRefPubMedPubMedCentral
23.
Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, Djoumbou Y, Mandal R, Aziat F, Dong E, et al. HMDB 3.0–the human metabolome database in 2013. Nucleic Acids Res. 2013;41:D801-807.CrossRefPubMed
24.
Smith CA, O’Maille G, Want EJ, Qin C, Trauger SA, Brandon TR, Custodio DE, Abagyan R, Siuzdak G. METLIN: a metabolite mass spectral database. Ther Drug Monit. 2005;27:747–51.CrossRefPubMed
25.
Horai H, Arita M, Kanaya S, Nihei Y, Ikeda T, Suwa K, Ojima Y, Tanaka K, Tanaka S, Aoshima K, et al. MassBank: a public repository for sharing mass spectral data for life sciences. J Mass Spectrom. 2010;45:703–14.CrossRefPubMed
26.
Yi Y, Fang Y, Wu K, Liu Y, Zhang W. Comprehensive gene and pathway analysis of cervical cancer progression. Oncol Lett. 2020;19:3316–32.PubMedPubMedCentral
27.
Guitart-Mampel M, Juarez-Flores DL, Youssef L, Moren C, Garcia-Otero L, Roca-Agujetas V, Catalan-Garcia M, Gonzalez-Casacuberta I, Tobias E, Milisenda JC, et al. Mitochondrial implications in human pregnancies with intrauterine growth restriction and associated cardiac remodelling. J Cell Mol Med. 2019;23:3962–73.CrossRefPubMedPubMedCentral
28.
Wlodek ME, Mibus A, Tan A, Siebel AL, Owens JA, Moritz KM. Normal lactational environment restores nephron endowment and prevents hypertension after placental restriction in the rat. J Am Soc Nephrol. 2007;18:1688–96.CrossRefPubMed
29.
Wlodek ME, Westcott K, Siebel AL, Owens JA, Moritz KM. Growth restriction before or after birth reduces nephron number and increases blood pressure in male rats. Kidney Int. 2008;74:187–95.CrossRefPubMed
30.
Schmidt IM, Chellakooty M, Boisen KA, Damgaard IN, Mau Kai C, Olgaard K, Main KM. Impaired kidney growth in low-birth-weight children: distinct effects of maturity and weight for gestational age. Kidney Int. 2005;68:731–40.CrossRefPubMed
31.
Spencer J, Wang Z, Hoy W. Low birth weight and reduced renal volume in Aboriginal children. Am J Kidney Dis. 2001;37:915–20.CrossRefPubMed
32.
Schreuder MF, Nauta J. Prenatal programming of nephron number and blood pressure. Kidney Int. 2007;72:265–8.CrossRefPubMed
33.
Schooneman MG, Vaz FM, Houten SM, Soeters MR. Acylcarnitines: reflecting or inflicting insulin resistance? Diabetes. 2013;62:1–8.CrossRefPubMed
34.
Mihalik SJ, Goodpaster BH, Kelley DE, Chace DH, Vockley J, Toledo FG, DeLany JP. Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity. Obesity (Silver Spring). 2010;18:1695–700.CrossRefPubMed
35.
Dambrova M, Makrecka-Kuka M, Kuka J, Vilskersts R, Nordberg D, Attwood MM, Smesny S, Sen ZD, Guo AC, Oler E, et al. Acylcarnitines: nomenclature, biomarkers, therapeutic potential, drug targets, and clinical trials. Pharmacol Rev. 2022;74:506–51.CrossRefPubMed
36.
Liu J, Chen XX, Li XW, Fu W, Zhang WQ. Metabolomic research on newborn infants with intrauterine growth restriction. Medicine (Baltimore). 2016;95:e3564.CrossRefPubMed
37.
38.
Toyohara T, Akiyama Y, Suzuki T, Takeuchi Y, Mishima E, Tanemoto M, Momose A, Toki N, Sato H, Nakayama M, et al. Metabolomic profiling of uremic solutes in CKD patients. Hypertens Res. 2010;33:944–52.CrossRefPubMed
39.
Sass JO, Mohr V, Olbrich H, Engelke U, Horvath J, Fliegauf M, Loges NT, Schweitzer-Krantz S, Moebus R, Weiler P, et al. Mutations in ACY1, the gene encoding aminoacylase 1, cause a novel inborn error of metabolism. Am J Hum Genet. 2006;78:401–9.CrossRefPubMedPubMedCentral
40.
Sirdah MM. Protective and therapeutic effectiveness of taurine in diabetes mellitus: a rationale for antioxidant supplementation. Diabetes Metab Syndr. 2015;9:55–64.CrossRefPubMed
41.
Lourenço R, Camilo ME. Taurine: a conditionally essential amino acid in humans? An overview in health and disease. Nutr Hosp. 2002;17:262–70.PubMed
42.
Marincola FC, Dessì A, Pattumelli MG, Corbu S, Ossicini C, Ciccarelli S, Agostino R, Mussap M, Fanos V. (1)H NMR-based urine metabolic profile of IUGR, LGA, and AGA newborns in the first week of life. Clin Chim Acta. 2015;451:28–34.CrossRefPubMed
43.
Austdal M, Silva GB, Bowe S, Thomsen LCV, Tangerås LH, Bjørge L, Bathen TF, Iversen AC. Metabolomics identifies placental dysfunction and confirms Flt-1 (FMS-like tyrosine kinase receptor 1) biomarker specificity. Hypertension. 2019;74:1136–43.CrossRefPubMed
44.
Economides DL, Nicolaides KH, Gahl WA, Bernardini I, Evans MI. Plasma amino acids in appropriate- and small-for-gestational-age fetuses. Am J Obstet Gynecol. 1989;161:1219–27.CrossRefPubMed
45.
Rehman T, Shabbir MA, Inam-Ur-Raheem M, Manzoor MF, Ahmad N, Liu ZW, Ahmad MH, Siddeeg A, Abid M, Aadil RM. Cysteine and homocysteine as biomarker of various diseases. Food Sci Nutr. 2020;8:4696–707.CrossRefPubMedPubMedCentral
46.
He B, Liu Y, Maurya MR, Benny P, Lassiter C, Li H, Subramaniam S, Garmire LX. The maternal blood lipidome is indicative of the pathogenesis of severe preeclampsia. J Lipid Res. 2021;62:100118.CrossRefPubMedPubMedCentral
47.
Shu F, Sugimura M, Kobayashi H, Kobayashi T, Kanayama N. Activated protein C prevents development of phosphatidylserine-induced intrauterine growth restriction in mice. Semin Thromb Hemost. 2001;27:99–105.CrossRefPubMed
48.
Hellmuth C, Uhl O, Standl M, Demmelmair H, Heinrich J, Koletzko B, Thiering E. Cord blood metabolome is highly associated with birth weight, but less predictive for later weight development. Obes Facts. 2017;10:85–100.CrossRefPubMedPubMedCentral
49.
Miranda J, Simões RV, Paules C, Cañueto D, Pardo-Cea MA, García-Martín ML, Crovetto F, Fuertes-Martin R, Domenech M, Gómez-Roig MD, et al. Metabolic profiling and targeted lipidomics reveals a disturbed lipid profile in mothers and fetuses with intrauterine growth restriction. Sci Rep. 2018;8:13614.CrossRefPubMedPubMedCentral
50.
Brown LD, Thorn SR, Cheung A, Lavezzi JR, Battaglia FC, Rozance PJ. Changes in fetal mannose and other carbohydrates induced by a maternal insulin infusion in pregnant sheep. J Anim Sci Biotechnol. 2014;5:28.CrossRefPubMedPubMedCentral
51.
Regnault TR, Teng C, de Vrijer B, Galan HL, Wilkening RB, Battaglia FC. The tissue and plasma concentration of polyols and sugars in sheep intrauterine growth retardation. Exp Biol Med (Maywood). 2010;235:999–1006.CrossRefPubMed
52.
Bovo S, Mazzoni G, Galimberti G, Calò DG, Fanelli F, Mezzullo M, Schiavo G, Manisi A, Trevisi P, Bosi P, et al. Metabolomics evidences plasma and serum biomarkers differentiating two heavy pig breeds. Animal. 2016;10:1741–8.CrossRefPubMed
53.
Hakim S, Bertucci MC, Conduit SE, Vuong DL, Mitchell CA. Inositol polyphosphate phosphatases in human disease. Curr Top Microbiol Immunol. 2012;362:247–314.PubMed
54.
Tang W, Zhang W, Azad MAK, Ma C, Zhu Q, Kong X. Metabolome, microbiome, and gene expression alterations in the colon of newborn piglets with intrauterine growth restriction. Front Microbiol. 2022;13:989060.CrossRefPubMedPubMedCentral
55.
Baserga M, Hale MA, Wang ZM, Yu X, Callaway CW, McKnight RA, Lane RH. Uteroplacental insufficiency alters nephrogenesis and downregulates cyclooxygenase-2 expression in a model of IUGR with adult-onset hypertension. Am J Physiol Regul Integr Comp Physiol. 2007;292:R1943-1955.CrossRefPubMed
Metadata
Title
Intrauterine growth restriction alters kidney metabolism at the end of nephrogenesis
Authors
Sheng-Yuan Ho
Merryl Esther Yuliana
Hsiu-Chu Chou
Chung-Ming Chen
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Nutrition & Metabolism / Issue 1/2023
Electronic ISSN: 1743-7075
DOI
https://doi.org/10.1186/s12986-023-00769-6

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