Obesity modifies the implantation window and disrupts intrauterine embryo positioning in rats

in Reproduction
Authors:
María Victoria Bazzano Universidad de Buenos Aires (UBA), Facultad de Ciencias Exactas y Naturales (FCEN), Buenos Aires, Argentina
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-UBA- Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Buenos Aires, Argentina

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Gisela Belén Sarrible Universidad de Buenos Aires (UBA), Facultad de Ciencias Exactas y Naturales (FCEN), Buenos Aires, Argentina
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-UBA- Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Buenos Aires, Argentina
UBA, FCEN, Departamento de Biodiversidad y Bilogía Experimental, Buenos Aires, Argentina

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Martín Berón de Astrada Universidad de Buenos Aires (UBA), Facultad de Ciencias Exactas y Naturales (FCEN), Buenos Aires, Argentina
UBA, FCEN, Departamento de Fisiología, Biología Molecular y Celular, Buenos Aires, Argentina
UBA, FCEN, Instituto de Biociencias, Biotecnología y Biología Traslacional (IB3), Buenos Aires, Argentina

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Evelin Elia Universidad de Buenos Aires (UBA), Facultad de Ciencias Exactas y Naturales (FCEN), Buenos Aires, Argentina
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-UBA- Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Buenos Aires, Argentina
UBA, FCEN, Departamento de Biodiversidad y Bilogía Experimental, Buenos Aires, Argentina

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Correspondence should be addressed to E Elia; E-mail: evelinmariel@gmail.com
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Obesity is a chronic disease that impairs female reproduction. When gestation is achieved, maternal obesity can cause offspring’s health complications. We intended to evaluate the effects of maternal pre-conceptional obesity on uterine contractile activity, embryo implantation and offspring development. Using cafeteria diet-induced obesity as an animal model, we found that maternal obesity delays embryo transport from the oviduct to the uterus and alters the intrauterine embryo positioning. Adrenergic receptor (AR) signaling is involved in embryo positioning, so all AR isoforms were screened in the pre-implantation uteri. We found that the β2AR is the dominant isoform in the rat uteri and that obesity causes its upregulation. Although β2AR activation is known to induce uterine relaxation, higher spontaneous contractile activity was detected in obese dams. Uteri from obese dams showed a higher sensitivity to salbutamol (a selective agonist of β2AR) than controls, consistent with the higher β2AR levels detected in those animals. Despite this, in obese dams, some embryos were still in the oviduct at the predicted time of initial embryo attachment, embryo implantation is successfully carried out since the total number of fetuses on gd 18.5 were similar between control and obese dams. These findings show that obesity is modifying the implantation window. Moreover, we found that maternal obesity resulted in macrosomia in the offspring, which is an important predictor of fetal programming of postnatal health. Hence, our results show that maternal obesity prior to pregnancy not only disturbs the implantation process, but also affects offspring development.

 

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  • WHO 2020 Noncommunicable Diseases Progress Monitor.

  • Akyol A, Langley-Evans SC & Mcmullen S 2009 Obesity induced by cafeteria feeding and pregnancy outcome in the rat. British Journal of Nutrition 102 16011 61 0. (https://doi.org/10.1017/S0007114509990961)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Akyol A, Mcmullen S & Langley-Evans SC 2012 Glucose intolerance associated with early-life exposure to maternal cafeteria feeding is dependent upon post-weaning diet. British Journal of Nutrition 107 9649 78. (https://doi.org/10.1017/S0007114511003916)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Alfaradhi MZ & Ozanne SE 2011 Developmental programming in response to maternal overnutrition. Frontiers in Genetics 2 27. (https://doi.org/10.3389/fgene.2011.00027)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Antoniotti GS, Coughlan M, Salamonsen LA & Evans J 2018 Obesity associated advanced glycation end products within the human uterine cavity adversely impact endometrial function and embryo implantation competence. Human Reproduction 33 654665. (https://doi.org/10.1093/humrep/dey029)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bazzano MV, Torelli C, Pustovrh MC, Paz DA & Elia EM 2015 Obesity induced by cafeteria diet disrupts fertility in the rat by affecting multiple ovarian targets. Reproductive Biomedicine Online 31 655667. (https://doi.org/10.1016/j.rbmo.2015.08.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bazzano MV, Paz DA & Elia EM 2017 Obesity alters the ovarian glucidic homeostasis disrupting the reproductive outcome of female rats. Journal of Nutritional Biochemistry 42 194202. (https://doi.org/10.1016/j.jnutbio.2017.01.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bazzano MV, Sarrible GB, Martinez N, Beron De Astrada M & Elia EM 2018 Obesity alters the uterine environment before pregnancy. Journal of Nutritional Biochemistry 62 181191. (https://doi.org/10.1016/j.jnutbio.2018.09.009)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bellver J, Ayllón Y, Ferrando M, Melo M, Goyri E, Pellicer A, Remohí J & Meseguer M 2010 Female obesity impairs in vitro fertilization outcome without affecting embryo quality. Fertility and Sterility 93 4474 54. (https://doi.org/10.1016/j.fertnstert.2008.12.032)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bellver J, Pellicer A, Garcia-Velasco JA, Ballesteros A, Remohi J & Meseguer M 2013 Obesity reduces uterine receptivity: clinical experience from 9,587 first cycles of ovum donation with normal weight donors. Fertility and Sterility 100 1050105 8. (https://doi.org/10.1016/j.fertnstert.2013.06.001)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Boney CM, Verma A, Tucker R & Vohr BR 2005 Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics 115 e290e29 6. (https://doi.org/10.1542/peds.2004-1808)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Borengasser SJ, Zhong Y, Kang P, Lindsey F, Ronis MJ, Badger TM, Gomez-Acevedo H & Shankar K 2013 Maternal obesity enhances white adipose tissue differentiation and alters genome-scale DNA methylation in male rat offspring. Endocrinology 154 411341 25. (https://doi.org/10.1210/en.2012-2255)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Catalano PM & Ehrenberg HM 2006 The short- and long-term implications of maternal obesity on the mother and her offspring. BJOG 113 112611 33. (https://doi.org/10.1111/j.1471-0528.2006.00989.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chaud MA, Franchi AM, Beron De Astrada M & Gimeno MF 1997 Role of nitric oxide on oxytocin-evoked contractions and prostaglandin synthesis in isolated pregnant rat uterus. Prostaglandins, Leukotrienes, and Essential Fatty Acids 57 32332 9. (https://doi.org/10.1016/s0952-3278(9790551-2)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen Q, Zhang Y, Peng H, Lei L, Kuang H, Zhang L, Ning L, Cao Y & Duan E 2011 Transient {beta}2-adrenoceptor activation confers pregnancy loss by disrupting embryo spacing at implantation. Journal of Biological Chemistry 286 434943 56. (https://doi.org/10.1074/jbc.M110.197202)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Elia EM, Pustovrh C, Amalfi S, Devoto L & Motta AB 2011 Link between metformin and the peroxisome proliferator-activated receptor gamma pathway in the uterine tissue of hyperandrogenized prepubertal mice. Fertility and Sterility 95 2534–253 7. (https://doi.org/10.1016/j.fertnstert.2011.02.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fanchin R, Righini C, Olivennes F, Taylor S, De Ziegler D & Frydman R 1998 Uterine contractions at the time of embryo transfer alter pregnancy rates after in-vitro fertilization. Human Reproduction 13 196819 74. (https://doi.org/10.1093/humrep/13.7.1968)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Howell KR & Powell TL 2017 Effects of maternal obesity on placental function and fetal development. Reproduction 153 R97R108. (https://doi.org/10.1530/REP-16-0495)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • IJland MM, Evers JL, Dunselman GA, Volovics L & Hoogland HJ 1997 Relation between endometrial wavelike activity and fecundability in spontaneous cycles. Fertility and Sterility 67 49249 6. (https://doi.org/10.1016/s0015-0282(9780075-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Johnsson IW, Haglund B, Ahlsson F & Gustafsson J 2015 A high birth weight is associated with increased risk of type 2 diabetes and obesity. Pediatric Obesity 10 7783. (https://doi.org/10.1111/ijpo.230)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Leopoldo AS, Lima-Leopoldo AP, Nascimento AF, Luvizotto RAM, Sugizaki MM, Campos DHS, Da Silva DCT, Padovani CR & Cicogna AC 2016 Classification of different degrees of adiposity in sedentary rats. Brazilian Journal of Medical and Biological Research = Revista Brasileira de Pesquisas Medicas e Biologicas 49 e5028. (https://doi.org/10.1590/1414-431X20155028)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Levin BE 2006 Metabolic imprinting: critical impact of the perinatal environment on the regulation of energy homeostasis. Philosophical Transactions of the Royal Society of London: Series B, Biological Sciences 361 110711 21. (https://doi.org/10.1098/rstb.2006.1851)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lutz TA & Woods SC 2012 Chapter 5 Overview of animal models of obesity. Current Protocols in Pharmacology 58 561. (https://doi.org/10.1002/0471141755.ph0561s58)

  • Murabayashi N, Sugiyama T, Zhang L, Kamimoto Y, Umekawa T, Ma N & Sagawa N 2013 Maternal high-fat diets cause insulin resistance through inflammatory changes in fetal adipose tissue. European Journal of Obstetrics, Gynecology, and Reproductive Biology 16 9 3944. (https://doi.org/10.1016/j.ejogrb.2013.02.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Parida S, Uttam Singh T, Ravi Prakash V & Mishra SK 2013 Molecular and functional characteristics of beta3-adrenoceptors in late pregnant mouse uterus: a comparison with beta2-adrenoceptors. European Journal of Pharmacology 700 747 9. (https://doi.org/10.1016/j.ejphar.2012.11.048)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Provost MP, Acharya KS, Acharya CR, Yeh JS, Steward RG, Eaton JL, Goldfarb JM & Muasher SJ 2016 Pregnancy outcomes decline with increasing body mass index: analysis of 239,127 fresh autologous in vitro fertilization cycles from the 2008–2010 Society for Assisted Reproductive Technology registry. Fertility and Sterility 105 663669. (https://doi.org/10.1016/j.fertnstert.2015.11.008)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Reilly JJ, Armstrong J, Dorosty AR, Emmett PM, Ness A, Rogers I, Steer C, Sherriff AAvon longitudinal study of parents and children study team 2005 Early life risk factors for obesity in childhood: cohort study. BMJ 330 1357. (https://doi.org/10.1136/bmj.38470.670903.E0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rothwell NJ & Stock MJ 1979a Combined effects of cafeteria and tube-feeding on energy balance in the rat. Proceedings of the Nutrition Society 38 5A. (https://doi.org/10.1079/pns19790026)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rothwell NJ & Stock MJ 1979b Regulation of energy balance in two models of reversible obesity in the rat. Journal of Comparative and Physiological Psychology 93 102410 34. (https://doi.org/10.1037/h0077631)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sakamoto K, Mccarthy A, Smith D, Green KA, Grahame Hardie D, Ashworth A & Alessi DR 2005 Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction. European Molecular Biology Organization 24 181018 20. (https://doi.org/10.1038/sj.emboj.7600667)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sclafani A & Springer D 1976 Dietary obesity in adult rats: similarities to hypothalamic and human obesity syndromes. Physiology and Behavior 17 4614 71. (https://doi.org/10.1016/0031-9384(7690109-8)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sewell MF, Huston-Presley L, Super DM & Catalano P 2006 Increased neonatal fat mass, not lean body mass, is associated with maternal obesity. American Journal of Obstetrics and Gynecology 195 1100110 3. (https://doi.org/10.1016/j.ajog.2006.06.014)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Shafat A, Murray B & Rumsey D 2009 Energy density in cafeteria diet induced hyperphagia in the rat. Appetite 52 343 8. (https://doi.org/10.1016/j.appet.2008.07.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Shankar K, Harrell A, Liu X, Gilchrist JM, Ronis MJ & Badger TM 2008 Maternal obesity at conception programs obesity in the offspring. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology 294 R528R5 38. (https://doi.org/10.1152/ajpregu.00316.2007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Van Der Steeg JW, Steures P, Eijkemans MJ, Habbema JD, Hompes PG, Burggraaff JM, Oosterhuis GJ, Bossuyt PM, Van Der Veen F & Mol BW 2008 Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women. Human Reproduction 23 32432 8. (https://doi.org/10.1093/humrep/dem371)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • White CL, Purpera MN & Morrison CD 2009 Maternal obesity is necessary for programming effect of high-fat diet on offspring. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology 296 R1464R14 72. (https://doi.org/10.1152/ajpregu.91015.2008)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zambrano E, Martínez-Samayoa PM, Rodríguez-González GL & Nathanielsz PW 2010 Dietary intervention prior to pregnancy reverses metabolic programming in male offspring of obese rats. Journal of Physiology 588 1791179 9. (https://doi.org/10.1113/jphysiol.2010.190033)

    • PubMed
    • Search Google Scholar
    • Export Citation