Hostname: page-component-76fb5796d-r6qrq Total loading time: 0 Render date: 2024-04-25T09:43:38.556Z Has data issue: false hasContentIssue false

Characterization of early changes in fetoplacental hemodynamics in a diet-induced rabbit model of IUGR

Published online by Cambridge University Press:  13 August 2015

J. López-Tello
Affiliation:
Department of Animal Production, Veterinary Faculty, Complutense University of Madrid, Madrid, Spain
A. Barbero
Affiliation:
Department of Animal Medicine and Surgery, Veterinary Faculty, Complutense University of Madrid, Madrid, Spain
A. González-Bulnes
Affiliation:
Comparative Physiology Lab, SGIT-INIA, Madrid, Spain Department of Veterinary Medicine, University of Sassari, Sassari, Italy
S. Astiz
Affiliation:
Comparative Physiology Lab, SGIT-INIA, Madrid, Spain
M. Rodríguez
Affiliation:
Department of Animal Production, Polytechnic University of Madrid, Madrid, Spain
N. Formoso-Rafferty
Affiliation:
Department of Animal Production, Veterinary Faculty, Complutense University of Madrid, Madrid, Spain
M. Arias-Álvarez
Affiliation:
Department of Animal Production, Veterinary Faculty, Complutense University of Madrid, Madrid, Spain
P. G. Rebollar*
Affiliation:
Department of Animal Production, Polytechnic University of Madrid, Madrid, Spain
*
*Address for correspondence: P. G. Rebollar, Department of Animal Production, Polytechnic University of Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain. (Email pilar.grebollar@upm.es)

Abstract

Intrauterine growth restriction (IUGR) is associated with adverse perinatal outcomes and late-onset diseases in offspring. Eating disorders, voluntary caloric restriction and maternal undernutrition can all induce IUGR but a relevant model is required to measure all its possible consequences. In this work, pregnant rabbits were used as an IUGR model. Control females (n=4) received ad libitum diet throughout pregnancy, whereas underfed females (n=5) were restricted to 50% of their daily requirements. Offspring size was measured by ultrasonography and in vivo at birth. Hemodynamic features of the umbilical cords and middle cerebral arteries (systolic peak velocity, end diastolic velocity, pulsatility index and resistance index) were characterized by Doppler ultrasonography. At day 21, maternal underfeeding resulted in a significant reduction of fetal size (occipito-nasal length). At birth, the size of kits from the underfed group was significantly lower (lower crown-rump length, biparietal and transversal thoracic diameters) and a reduced weight with respect to the control group. Feed restriction altered blood flow perfusion compared with does fed ad libitum (significant higher systolic peak, time-averaged mean velocities and lower end diastolic velocity). Fetuses affected by IUGR presented with compensative brain-sparing effects when compared with the control group. In conclusion, the present study supports using rabbits and the underfeeding approach as a valuable model for IUGR studies. These results may help to characterize IUGR alterations due to nutrient restriction of mothers in future research.

Type
Original Article
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2015 

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. Brett, KE, Ferraro, ZM, Yockell-Lelievre, J, Gruslin, A, Adamo, KB. Maternal–fetal nutrient transport in pregnancy pathologies: the role of the placenta. Int J Mol Sci. 2014; 15, 1615316185.CrossRefGoogle ScholarPubMed
2. Ramakrishnan, U, Imhoff-Kunsch, B, Martorell, R. Maternal nutrition interventions to improve maternal, newborn, and child health outcomes. Nestle Nutr Inst Workshop Ser. 2014; 78, 7180.Google Scholar
3. Murthy, LS, Agarwal, KN, Khanna, S. Placental morphometric and morphologic alterations in maternal undernutrition. Am J Obstet Gynecol. 1976; 124, 641646.Google Scholar
4. Chia, CC, Huang, SC. Overview of fetal growth retardation/restriction. Taiwan J Obstet Gynecol. 2014; 3, 435440.CrossRefGoogle Scholar
5. Bhutta, ZA, Das, JK, Rizvi, A, et al. Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost? Lancet. 2013; 382, 452477.CrossRefGoogle ScholarPubMed
6. Cetin, I, Mando, C, Calabrese, S. Maternal predictors of intrauterine growth restriction. Curr Opin Clin Nutr Metab Care. 2013; 16, 310319.Google Scholar
7. Nardozza, LM, Araujo Junior, E, Barbosa, MM, et al. Fetal growth restriction: current knowledge to the general Obs/Gyn. Arch Gynecol Obstet. 2012; 286, 113.Google Scholar
8. Ergaz, Z, Avgil, M, Ornoy, A. Intrauterine growth restriction-etiology and consequences: what do we know about the human situation and experimental animal models? Reprod Toxicol. 2005; 20, 301322.CrossRefGoogle ScholarPubMed
9. Redmer, DA, Wallace, JM, Reynolds, LP. Effect of nutrient intake during pregnancy on fetal and placental growth and vascular development. Domest Anim Endocrinol. 2004; 27, 199217.Google Scholar
10. Gonzalez-Bulnes, A, Ovilo, C, Lopez-Bote, CJ, et al. Fetal and early-postnatal developmental patterns of obese-genotype piglets exposed to prenatal programming by maternal over- and undernutrition. Endocr Metab Immune Disord Drug Targets. 2013; 13, 240249.CrossRefGoogle ScholarPubMed
11. Ross, MG, Desai, M. Developmental programming of offspring obesity, adipogenesis, and appetite. Clin Obstet Gynecol. 2013; 56, 529536.Google Scholar
12. Barker, DJ. In utero programming of cardiovascular disease. Theriogenology. 2000; 53, 555574.Google Scholar
13. Saffery, R. Epigenetic change as the major mediator of fetal programming in humans: are we there yet? Ann Nutr Metab. 2014; 64, 203207.Google Scholar
14. Schroder, HJ. Models of fetal growth restriction. Eur J Obstet Gynecol Reprod Biol. 2003; 110, S29S39.Google Scholar
15. Puschel, B, Daniel, N, Bitzer, E, et al. The rabbit (Oryctolagus cuniculus): a model for mammalian reproduction and early embryology. Cold Spring Harb Protoc. 2010; 2010, pdb.emo139.Google Scholar
16. Fischer, B, Chavatte-Palmer, P, Viebahn, C, Santos, AN, Duranthon, V. Rabbit as a reproductive model for human health. Reproduction. 2012; 144, 110.Google Scholar
17. Russell, WMS, Burch, RL, Hume, CW. The Principles of Humane Experimental Technique. 1959. Universities Federation for Animal Welfare: Wheathampstead, England.Google Scholar
18. Derrick, M, Drobyshevsky, A, Ji, X, et al. Hypoxia–ischemia causes persistent movement deficits in a perinatal rabbit model of cerebral palsy: assessed by a new swim test. Int J Dev Neurosci. 2009; 27, 549557.Google Scholar
19. van Vliet, E, Eixarch, E, Illa, M, et al. Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain. PLoS One. 2013; 8, e64545.CrossRefGoogle ScholarPubMed
20. Chavatte-Palmer, P, Laigre, P, Simonoff, E, et al. In utero characterisation of fetal growth by ultrasound scanning in the rabbit. Theriogenology. 2008; 69, 859869.Google Scholar
21. Huizinga, CT, Engelbregt, MJ, Rekers-Mombarg, LT, et al. Ligation of the uterine artery and early postnatal food restriction – animal models for growth retardation. Horm Res. 2004; 62, 233240.Google Scholar
22. Eixarch, E, Hernandez-Andrade, E, Crispi, F, et al. Impact on fetal mortality and cardiovascular Doppler of selective ligature of uteroplacental vessels compared with undernutrition in a rabbit model of intrauterine growth restriction. Placenta. 2011; 32, 304309.CrossRefGoogle Scholar
23. Rebollar, PG, Dal Bosco, A, Millán, P, et al. Ovulating induction methods in rabbit does: the pituitary and ovarian responses. Theriogenology. 2012; 77, 292298.Google Scholar
24. Hoffman, LH, Breinan, DR, Blaeuer, GL. The rabbit as a model for implantation: in vivo and in vitro studies. In Embryo Implantation: Molecular, Cellular, and Clinical Aspects (ed. Carson DD), 1999; pp. 151160. Springer-Verlag: New York, NY.Google Scholar
25. Hafez, ES, Tsutsumi, Y. Changes in endometrial vascularity during implantation and pregnancy in the rabbit. Am J Anat. 1966; 118, 249282.Google Scholar
26. Vik, T, Vatten, L, Jacobsen, G, Bakketeig, LS. Prenatal growth in symmetric and asymmetric small-for-gestational-age infants. Early Hum Dev. 1997; 48, 167176.Google Scholar
27. Smarr, MM, Vadillo-Ortega, F, Castillo-Castrejon, M, O’Neill, MS. The use of ultrasound measurements in environmental epidemiological studies of air pollution and fetal growth. Curr Opin Pediatr. 2013; 25, 240246.Google Scholar
28. Smith, GC, Smith, MF, McNay, MB, Fleming, JE. First-trimester growth and the risk of low birth weight. N Engl J Med. 1998; 339, 18171822.Google Scholar
29. Pedersen, NG, Wojdemann, KR, Scheike, T, Tabor, A. Fetal growth between the first and second trimesters and the risk of adverse pregnancy outcome. Ultrasound Obstet Gynecol. 2008; 32, 147154.Google Scholar
30. Kelly, RW, Newnham, JP. Estimation of gestational age in Merino ewes by ultrasound measurement of fetal head size. Aust J Agri Res. 1989; 40, 12931299.Google Scholar
31. Beaudoin, S, Barbet, P, Bargy, F. Developmental stages in the rabbit embryo: guidelines to choose an appropriate experimental model. Fetal Diagn Ther. 2003; 18, 422427.Google Scholar
32. Vernon, RG, Clegg, RA, Flint, DJ. Adaptations of adipose tissue metabolism and number of insulin receptors in pregnant sheep. Comp Biochem Physiol B. 1985; 81, 909913.Google Scholar
33. Symonds, ME, Clarke, L. Nutrition-environment interactions in pregnancy. Nutr Res Rev. 1996; 9, 135148.Google Scholar
34. Nafeaa, A, Ahmed, SA, Fat Hallah, S. Effect of feed restriction during pregnancy on performance and productivity of New Zealand white rabbit does. Vet Med Int. 2011; 2011, 839737.Google Scholar
35. Menchetti, L, Brecchia, G, Cardinali, R, Polisca, A, Boiti, C. Food restriction during pregnancy: effects on body condition and productive performance of primiparous rabbit does. World Rabbit Sci. 2015; 23, 18.CrossRefGoogle Scholar
36. Fowden, AL, Moore, T. Maternal-fetal resource allocation: co-operation and conflict. Placenta. 2012; 33, 1115.Google Scholar
37. Ichizuka, K, Ando, S, Ichihara, M. Application of high-intensity focused ultrasound for umbilical artery occlusion in a rabbit model. Ultrasound Obstet Gynecol. 2007; 30, 4751.Google Scholar
38. Hershkovitz, R, Kingdom, JCP, Geary, M, Rodeck, CH. Fetal cerebral blood flow redistribution in late gestation: identification of compromise in small fetuses with normal umbilical artery Doppler. Ultrasound Obstet Gynecol. 2000; 15, 209212.Google Scholar
39. Polisca, A, Scotti, L, Orlandi, R, Brecchia, G, Boiti, C. Doppler evaluation of maternal and fetal vessels during normal gestation in rabbits. Theriogenology. 2010; 73, 358366.Google Scholar
40. Gudmundsson, S, Marsal, K. Umbilical artery and uteroplacental blood flow velocity waveforms in normal pregnancy – a crosssectional study. Eur J Obstet Gynaecol. 1988; 67, 347354.Google Scholar
41. Acharya, G, Wilsgaard, T, Berntsen, GK, Maltau, JM, Kiserud, T. Reference ranges for serial measurements of blood velocity and pulsatility index at the intra-abdominal portion, and fetal and placental ends of the umbilical artery. Ultrasound Obstet Gynecol. 2005; 26, 162169.Google Scholar
42. Bamfo, JE, Odibo, AO. Diagnosis and management of fetal growth restriction. J Pregnancy. 2011; 2011, 640715.CrossRefGoogle ScholarPubMed
43. Roberts, JM. Pathophysiology of ischemic placental disease. Semin Perinat. 2014; 38, 139145.Google Scholar
44. Makhseed, M, Jirous, J, Ahmed, MA, Viswanathan, DL. Middle cerebral artery to umbilical artery resistance index ratio in the prediction of neonatal outcome. Int J Gynaecol Obstet. 2000; 71, 119125.Google Scholar
45. Peeling, AN, Smart, JL. Review of literature showing that undernutrition affects the growth rate of all processes in the brain to the same extent. Metab Brain Dis. 1994; 9, 3342.Google Scholar
46. Salihagic-Kadic, A, Medic, M, Jugovic, D, et al. Fetal cerebrovascular response to chronic hypoxia – implications for the prevention of brain damage. J Matern Fetal Neonatal Med. 2006; 19, 387396.Google Scholar
47. Baschat, AA, Gembruch, U. The cerebroplacental Doppler ratio revisited. Ultrasound Obstet Gynecol. 2003; 21, 124127.Google Scholar
48. Mossman, HW. The rabbit placenta and the problem of placental transmission. Am J Anat. 1926; 37, 433497.Google Scholar
49. Hecher, K, Campbell, S, Doyle, P, Harrington, K, Nicolaides, K. Assessment of fetal compromise by Doppler ultrasound investigation of the fetal circulation arterial, intracardiac, and venous blood flow velocity studies. Circulation. 1995; 91, 129138.Google Scholar