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Morphological markers of hypoxia in the fetal kidney with placental insufficiency treated with neuro-EPO: study in rats.

Nínive Nuñez López, Yaima Nova Bonet, Aida María Suárez Aguiar, Laymit Alonso Padilla, Yordanca Morgado Gamboa, Laura López Marín

Article ID: 2098
Vol 3, Issue 2, 2022

DOI: https://doi.org/10.54517/urr.v2i2.2098
VIEWS - 29 (Abstract)

Abstract

Foundation: intrauterine growth restriction constitutes a complication of pregnancy. Newborns with this condition are exposed to an increased risk of perinatal and postnatal morbidity and mortality.

Objective: to evaluate morphological markers of hypoxia in fetal and kidney development, using a model of placental insufficiency treated with human erythropoietin with low sialic acid content (neuro-Epo) in rats.

Methods: three groups of gestated rats from the Wistar line were used. A control group (group I) and two experimental groups (groups II and III) with six rats each. Rats of groups II and III had uterine artery ligation on day 16 of pregnancy (E 16). Group III from E16 to E19 was administered a dose of 0.5 mg / kg / day of neuro-Epo subcutaneously and group II was administered placebo. On the 20th day of gestation the fetuses and their placentas were weighed. The fetuses' size and cephalic diameters were measured. Morphometric and histological features in the fetal kidney were studied with hematoxylin-eosin staining and PAS. A qualitative histopathological analysis of their cell types was performed.

Results: fetuses with intrauterine growth restriction did not improve growth markers. Hypoxia lesions were found in the fetal kidney of the untreated IUGR group that improved by administering neuro-Epo.

Conclusions: the administration of neuro-Epo only showed reparative and protective effects on histological alterations caused by hypoxia in the fetal kidney.

Keywords

hypoxia; fetal hypoxia; kidney; placental insufficiency; erythropoietin; rats; Wistar

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References

1. Langley SC. Nutrition in early life and the programming of adult disease. A Review. J Hum Nutr Diet. 2014; 28: 1-14.

2. Calkins K, Devaskar SU. Fetal Origins of Adult Disease. Current Problems in Pediatric and Adolescent Health Care. 2011; 41 (6): 158-76.

3. Molina S, Correa DM, Rojas JL, Acuña E. Fetal origins of adult pathology: intrauterine growth restriction as a risk factor. Rev Chil Obstet Gynecol. 2014; 79 (6): 546-53.

4. Krause B, Sobrevia L, Castillo P. Role of the placenta in fetal programming of adult chronic diseases. Buenos Aires: FONDECYT Program; 2009.

5. Nüsken E, Dötsch J, Weber LT, Nüsken KD. Developmental Programming of Renal Function and Re-Programming Approaches. Front. Pediatr. 2018; 6: 36.

6. Gurusinghe S, Tambay A, Sethna CB. Developmental Origins and Nephron Endowment in Hypertension. Front Pediatr. 2017; 5: 151.

7. Doro GF, Serna J, Sacramento A. Renal vascularization indexes and fetal hemodynamics in fetuses with growth restriction. University of Sao Paulo, Brazil. Prenatal Diagnosis. 2017; 37: 837-42.

8. Vittori D, Chamorro ME, Nesse A. Erythropoietin as an erythropoietic and non-erythropoietic agent: therapeutic considerations. University of Buenos Aires. Argentina. Acta Bioquim Clin Latinoam. 2016; 50 (4): 773-82.

9. Suzuki N. Erythropoietin Gene Expression: Developmental-Stage Specificity, Cell-Type Specificity, and Hypoxia Inducibility. Tohoku J Exp Med. 2015; 235 (3): 233-40.

10. Provatopoulou ST, Ziroyiannis PN. Clinical use of erythropoietin in chronic kidney disease: outcomes and future prospects. HIPPOKRATIA. 2011; 15 (2): 109-15.

11. Yu j, Yu Z, Ming L, Mei D, Wei W, Da L. EPO improves the proliferation and inhibits apoptosis of trophoblast and decidual stromal cells through activating STAT5 and inactivating p38 signal in human early pregnancy. Int J Clin Pathol. 2011; 4 (8): 765-74.

12. Bahlmann FH, Fliser D. Erythropoietin and renoprotection. Curr Opin Nephrol Hypertens. 2009; 18: 15-20.

13. Muñoz A, García JC, Pardo Z, García JD, Sosa I, Curbelo D, et al. Nasal formulations of EPORH with low sialic acid content for the treatment of nervous system diseases [Internet]. Havana: CIDEM; 2007. [cited 18 Apr 2018]Available from: https://patentscope.wipo.int/search/es/detail.jsf?d ocId=WO2007009404.

14. Alfonso C, Tome O. Experimental obtaining of intrauterine growth retarded offspring. Revista Cubana Cienc Vet. 2000; 26 (1): 39-41.

15. Pereira M, Barini R, Lanhella FL, Plutarco R, Sbragia L. Experimental model for fetal growth restriction in rats: effect on intestinal and renal glycogenesis and morphometry. Rev Bras Ginecol Obstet. 2010; 32 (4): 163-8.

16. Camprubi M, Ortega A, Balaguer A, Iglesias I, Girabent M, Callejo J, Figueras. J, Krauel X. Cauterization of meso-ovarian vessels, a new model of intrauterine growth restriction in rats. Placenta. 2009; 30: 761-66.

17. Morgado Y. Influence of human neuroerythropoietin on placental morphology and fetal growth in an experimental model of intrauterine growth retardation in rat [Thesis]. Havana: Havana Institute of Medical Sciences; 2017.

18. Burton GJ, Fowden AL. Review: The placenta and developmental programming: Balancing fetal nutrient demands with maternal resource allocation. Placenta. 2012; 33: S23-S27.

19. Ramirez R. Fetal programming of adult arterial hypertension: cellular and molecular mechanism. Rev Colomb Cardiol. 2013; 20 (1): 23-32.

20. Nüsken E, Wolhlfarth M, Lippach G, Rauh M, Sheneider H, Nüsken KD. Reduce Perinatal Leptin availability may contribute to adverse metabolic programming in rat model of uteroplacental insufficiency. Endocrinology. 2016; 157: 1816-25.

21. Plank Ch, Nüsken KD, Menendez-Castro C, Hartner A. Intrauterine Growth Restriction following Ligation of the Uterine Arteries Leads to More Severe Glomerulosclerosis after Mesangio proliferative Glomerulonephritis in the Offspring. Am J Nephrol. 2010; 32: 287-95.

22. Cotran RS, Kumar V, Collins T, Abbas AK. Robbins. Structural and functional pathology. Barcelona: Elsevier; 2013.

23. De Beuf A, Hou X, D'Haese PC, Verhulst A. Epoetin Delta Reduces Oxidative Stress in Primary Human Renal Tubular Cells. J Biomed Biotechnol. 2010; 2010: 395785.

24. Imamura R, Moriyama T, Isaka Y, Namba Y, Ichimaru N, Takahara Sh. Erythropoietin Protects the Kidneys Against Ischemia Reperfusion Injury by Activating Hypoxia Inducible Factor-1. Transplantation. 2007; 83 (10): 1371-9.

25. Ma YS, Zhou J, Liu H, Du Y, Lin XM. Erythropoietin through the placenta barrier and fetal blood-brain barrier with transient uteroplacental ischemia. Sichuan Da Xue Xue Bao Yi Xue Ban. 2012; 43 (5): 687-9.

26. Sienas L, Wong T, Collins R, Smith J. Contemporary Uses of Erythropoietin in Pregnancy. Obstetrical Gynecological Survey. 2013; 68 (8): 594-602.