Hostname: page-component-586b7cd67f-g8jcs Total loading time: 0 Render date: 2024-11-28T04:26:22.608Z Has data issue: false hasContentIssue false

Pre-gestational overweight in guinea pig sows induces fetal vascular dysfunction and increased rate of large and small fetuses

Published online by Cambridge University Press:  22 October 2015

B. J. Krause*
Affiliation:
Division of Obstetrics & Gynaecology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
E. A. Herrera
Affiliation:
Programa de Fisiopatología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
F. A. Díaz-López
Affiliation:
Division of Obstetrics & Gynaecology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile Programa de Fisiopatología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
M. Farías
Affiliation:
Division of Obstetrics & Gynaecology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
R. Uauy
Affiliation:
Division of Paediatrics, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
P. Casanello
Affiliation:
Division of Obstetrics & Gynaecology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile Division of Paediatrics, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
*
*Address for correspondence: Dr. B. J. Krause, Division of Obstetrics and Gynaecology, School of Medicine, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, Chile. (Email [email protected])

Abstract

In humans, obesity before and during pregnancy is associated with both fetal macrosomia and growth restriction, and long-term cardiovascular risk in the offspring. We aimed to determine whether overweighted pregnant guinea pig sows results in an increased fetal weight at term and the effects on the vascular reactivity in fetal systemic and umbilical arteries. Pregnant guinea pigs were classified as control (n=4) or high weight (HWS, n=5) according to their pre-mating weight, and their fetuses extracted at 0.9 gestation (~60 days). Segments of fetal femoral and umbilical arteries were mounted in a wire myograph, where the contractile response to KCl (5–125 mM), and the relaxation to nitric oxide synthase-dependent agents (insulin, 10−10–10−7 and acetylcholine, 10−10–10−5) and nitric oxide [sodium nitroprusside (SNP), 10−10–10−5] were determined. Fetuses from HWS (HWSF) were grouped according to their body weight as low (<76 g) or high (>85 g) fetal weight, based on the confidence interval (76.5–84.9 g) of the control group. No HWSF were observed in the normal range. Umbilical arteries from HWSF showed a lower response to KCl and insulin compared with controls, but a comparable response with SNP. Conversely, femoral arteries from HWSF showed an increased response to KCl and acetylcholine, along with a decreased sensitivity to SNP. These data show that overweight sows have altered fetal growth along gestation. Further, large and small fetuses from obese guinea pig sows showed altered vascular reactivity at umbilical and systemic vessels, which potentially associates with long-term cardiovascular risk.

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. Higgins, L, Greenwood, SL, Wareing, M, Sibley, CP, Mills, TA. Obesity and the placenta: a consideration of nutrient exchange mechanisms in relation to aberrant fetal growth. Placenta. 2011; 32, 17.Google Scholar
2. Reynolds, RM, Allan, KM, Raja, EA, et al. Maternal obesity during pregnancy and premature mortality from cardiovascular event in adult offspring: follow-up of 1 323 275 person years. BMJ. 2013; 347, f4539.Google Scholar
3. Edvardsson, VO, Steinthorsdottir, SD, Eliasdottir, SB, Indridason, OS, Palsson, R. Birth weight and childhood blood pressure. Curr Hypertens Rep. 2012; 14, 596602.Google Scholar
4. McGuire, W, Dyson, L, Renfrew, M. Maternal obesity: consequences for children, challenges for clinicians and carers. Semin Fetal Neonatal Med. 2010; 15, 108112.Google Scholar
5. Ornellas, F, Souza-Mello, V, Mandarim-de-Lacerda, CA, Aguila, MB. Programming of obesity and comorbidities in the progeny: lessons from a model of diet-induced obese parents. PLoS One. 2015; 10, e0124737.Google Scholar
6. Hayward, CE, Higgins, L, Cowley, EJ, et al. Chorionic plate arterial function is altered in maternal obesity. Placenta. 2013; 34, 281287.Google Scholar
7. Schneider, D, Hernandez, C, Farias, M, Uauy, R, Krause, BJ, Casanello, P. Oxidative stress as common trait of endothelial dysfunction in chorionic arteries from fetuses with IUGR and LGA. Placenta. 2015; 36, 552558.CrossRefGoogle ScholarPubMed
8. Yu, Z, Han, S, Zhu, J, et al. Pre-pregnancy body mass index in relation to infant birth weight and offspring overweight/obesity: a systematic review and meta-analysis. PLoS One. 2013; 8, e61627.Google Scholar
9. Li, M, Reynolds, CM, Sloboda, DM, Gray, C, Vickers, MH. Effects of taurine supplementation on hepatic markers of inflammation and lipid metabolism in mothers and offspring in the setting of maternal obesity. PLoS One. 2013; 8, e76961.Google Scholar
10. Gurecka, R, Koborova, I, Jansakova, K, et al. Prenatal dietary load of Maillard reaction products combined with postnatal Coca-Cola drinking affects metabolic status of female Wistar rats. Croat Med J. 2015; 56, 94103.Google Scholar
11. Toop, CR, Muhlhausler, BS, O’Dea, K, Gentili, S. Consumption of sucrose, but not high fructose corn syrup, leads to increased adiposity and dyslipidaemia in the pregnant and lactating rat. J Dev Orig Health Dis. 2015; 6, 3846.Google Scholar
12. Sloboda, DM, Howie, GJ, Pleasants, A, Gluckman, PD, Vickers, MH. Pre- and postnatal nutritional histories influence reproductive maturation and ovarian function in the rat. PLoS One. 2009; 4, e6744.CrossRefGoogle ScholarPubMed
13. Connor, KL, Vickers, MH, Beltrand, J, Meaney, MJ, Sloboda, DM. Nature, nurture or nutrition? Impact of maternal nutrition on maternal care, offspring development and reproductive function. J Physiol. 2012; 590(Pt 9), 21672180.Google Scholar
14. Luzzo, KM, Wang, Q, Purcell, SH, et al. High fat diet induced developmental defects in the mouse: oocyte meiotic aneuploidy and fetal growth retardation/brain defects. PLoS One. 2012; 7, e49217.CrossRefGoogle ScholarPubMed
15. Busso, D, Mascareno, L, Salas, F, et al. Early onset intrauterine growth restriction in a mouse model of gestational hypercholesterolemia and atherosclerosis. Biomed Res Int. 2014; 2014, 280497.Google Scholar
16. Michel, CL, Bonnet, X. Influence of body condition on reproductive output in the guinea pig. J Exp Zool Part A Ecol Genet Physiol. 2012; 317, 2431.CrossRefGoogle ScholarPubMed
17. Turner, AJ, Trudinger, BJ. A modification of the uterine artery restriction technique in the guinea pig fetus produces asymmetrical ultrasound growth. Placenta. 2009; 30, 236240.Google Scholar
18. Krause, BJ, Prieto, CP, Munoz-Urrutia, E, et al. Role of arginase-2 and eNOS in the differential vascular reactivity and hypoxia-induced endothelial response in umbilical arteries and veins. Placenta. 2012; 33, 360366.CrossRefGoogle ScholarPubMed
19. Mulvany, MJ, Aalkjaer, C. Structure and function of small arteries. Physiol Rev. 1990; 70, 921961.Google Scholar
20. Delaey, C, Boussery, K, Van de Voorde, J. Contractility studies on isolated bovine choroidal small arteries: determination of the active and passive wall tension-internal circumference relation. Exp Eye Res. 2002; 75, 243248.Google Scholar
21. Turner, AJ, Trudinger, BJ. Ultrasound measurement of biparietal diameter and umbilical artery blood flow in the normal fetal guinea pig. Comp Med. 2000; 50, 379384.Google ScholarPubMed
22. Santangeli, L, Sattar, N, Huda, SS. Impact of maternal obesity on perinatal and childhood outcomes. Best Pract Res Clin Obstet Gynaecol. 2015; 29, 438448.Google Scholar
23. King, JC. Maternal obesity, metabolism, and pregnancy outcomes. Annu Rev Nutr. 2006; 26, 271291.Google Scholar
24. Santolaya, J, Kahn, D, Nobles, G, Ramakrishnan, V, Warsof, SL. Ultrasonographic growth and Doppler hemodynamic evaluation of fetuses of obese women. J Reprod Med. 1994; 39, 690694.Google Scholar
25. Quintero-Prado, R, Bugatto, F, Sanchez-Martin, P, et al. The influence of placental perfusion on birthweight in women with gestational diabetes. J Matern Fetal Neonatal Med. 2014; 27, 14.Google Scholar
26. Ece, I, Uner, A, Balli, S, et al. The effects of pre-pregnancy obesity on fetal cardiac functions. Pediatr Cardiol. 2014; 35, 838843.Google Scholar
27. Ingul, CB, Loras, L, Tegnander, E, Eik-Nes, SH, Brantberg, A. Maternal obesity affects foetal myocardial function already in first trimester. Ultrasound Obstet Gynecol . 2015; doi: 10.1002/uog.14841.Google Scholar
28. Sarno, L, Maruotti, GM, Saccone, G, et al. Maternal body mass index influences umbilical artery Doppler velocimetry in physiologic pregnancies. Prenat diagn. 2015; 35, 125128.CrossRefGoogle ScholarPubMed
29. Khoury, J, Knutsen, M, Stray-Pedersen, B, Thaulow, E, Tonstad, S. A lower reduction in umbilical artery pulsatility in mid-pregnancy predicts higher infant blood pressure six months after birth. Acta Paediatr. 2015; doi: 10.1111/apa.13020.Google Scholar
30. Fraser, A, Tilling, K, Macdonald-Wallis, C, et al. Association of maternal weight gain in pregnancy with offspring obesity and metabolic and vascular traits in childhood. Circulation. 2010; 121, 25572564.Google Scholar
31. Fan, L, Lindsley, SR, Comstock, SM, et al. Maternal high-fat diet impacts endothelial function in nonhuman primate offspring. Int J Obes (Lond). 2013; 37, 254262.Google Scholar
32. Gray, C, Vickers, MH, Segovia, SA, Zhang, XD, Reynolds, CM. A maternal high fat diet programmes endothelial function and cardiovascular status in adult male offspring independent of body weight, which is reversed by maternal conjugated linoleic acid (CLA) supplementation. PLoS One. 2015; 10, e0115994.CrossRefGoogle ScholarPubMed
33. Begg, LM, Palma-Dias, R, Wang, J, Chin-Dusting, JP, Skilton, MR. Maternal adiposity and newborn vascular health. Arch Dis Child Fetal Neonatal Ed. 2013; 98, F279F280.Google Scholar
34. Dollberg, S, Marom, R, Mimouni, FB, Yeruchimovich, M. Normoblasts in large for gestational age infants. Arch Dis Child Fetal Neonatal Ed. 2000; 83, F148F149.Google Scholar
35. Sheffer-Mimouni, G, Mimouni, FB, Dollberg, S, et al. Neonatal nucleated red blood cells in infants of overweight and obese mothers. J Am Coll Nutr. 2007; 26, 259263.CrossRefGoogle ScholarPubMed
36. Camm, EJ, Hansell, JA, Kane, AD, et al. Partial contributions of developmental hypoxia and undernutrition to prenatal alterations in somatic growth and cardiovascular structure and function. Am J Obstet Gynecol. 2010; 203(495), e424-434.Google Scholar
37. Giussani, DA, Davidge, ST. Developmental programming of cardiovascular disease by prenatal hypoxia. J Dev Orig Health Dis. 2013; 4, 328337.Google Scholar
Supplementary material: Image

Krause supplementary material

Figure S1

Download Krause supplementary material(Image)
Image 856.1 KB
Supplementary material: Image

Krause supplementary material

Figure S2

Download Krause supplementary material(Image)
Image 3.4 MB